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Anxiety

MedGen UID:
1613
Concept ID:
C0003467
Finding; Mental or Behavioral Dysfunction
Synonym: Anxiety-related personality traits
SNOMED CT: Anxiousness (48694002); Feeling anxious (48694002); Anxiety reaction (48694002); Anxiety (48694002)
 
Gene (location): SLC6A4 (17q11.2)
 
HPO: HP:0000739
Monarch Initiative: MONDO:0011918
OMIM®: 607834

Definition

Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control. [from HPO]

Conditions with this feature

Lipomatosis dolorosa
MedGen UID:
1757
Concept ID:
C0001529
Disease or Syndrome
Adiposis dolorosa, also known as Dercum disease, is characterized by generalized obesity and pronounced, disabling, and chronic pain in the adipose tissue of the proximal extremities, trunk, pelvic area, and buttocks; the face and hands are usually spared. There are a number of associated symptoms, including multiple lipomas, generalized weakness, fatigue, sleep disturbances, constipation, and psychiatric abnormalities. It is 5 to 30 times more common in women than men, and usually presents between 35 and 50 years of age (summary by Campen et al., 2001; review by Hansson et al., 2012). Based on a review of the literature and studies of 111 patients, Hansson et al. (2012) proposed a classification of Dercum disease into 4 types: (I) generalized diffuse form without clear lipomas, (II) generalized nodular form with multiple lipomas, (III) localized nodular form, and (IV) juxtaarticular form with solitary fatty deposits near joints.
5p partial monosomy syndrome
MedGen UID:
41345
Concept ID:
C0010314
Disease or Syndrome
Cri-du-chat syndrome was first described by Lejeune et al. (1963) as a hereditary congenital syndrome associated with deletion of part of the short arm of chromosome 5. The deletions can vary in size from extremely small and involving only band 5p15.2 to the entire short arm. Although the majority of deletions arise as new mutations, approximately 12% result from unbalanced segregation of translocations or recombination involving a pericentric inversion in one of the parents.
Obsessive-compulsive disorder
MedGen UID:
14445
Concept ID:
C0028768
Mental or Behavioral Dysfunction
Obsessive-compulsive disorder (OCD) is characterized by recurring obsessions and/or compulsions and has been estimated to affect nearly 5 million people in the United States (Karno et al., 1988). Evidence for a strong genetic component in OCD comes from twin studies, family genetics studies, and segregation analyses, as reviewed by Alsobrook et al. (2002). Zhang et al. (2002) suggested that hoarding is likely to be an evolutionarily conserved trait that, in times of adversity, was associated with increased survival and reproductive fitness. However, extreme forms of this trait are associated with marked disability and poor response to treatment (Black et al., 1998; Mataix-Cols et al., 1999).
Phenylketonuria
MedGen UID:
19244
Concept ID:
C0031485
Disease or Syndrome
Phenylalanine hydroxylase (PAH) deficiency results in intolerance to the dietary intake of the essential amino acid phenylalanine and produces a spectrum of disorders. The risk of adverse outcome varies based on the degree of PAH deficiency. Without effective therapy, most individuals with severe PAH deficiency, known as classic PKU, develop profound and irreversible intellectual disability. Affected individuals on an unrestricted diet who have phenylalanine levels above normal but below 1,200 µmol/L (20 mg/dL) are at much lower risk for impaired cognitive development in the absence of treatment.
Stiff-man syndrome
MedGen UID:
39017
Concept ID:
C0085292
Disease or Syndrome
The stiff-person syndrome (SPS) is most often an adult-onset sporadic acquired disorder characterized by progressive muscle stiffness with superimposed painful muscle spasms accompanied by electromyographic evidence of continuous motor activity at rest. SPS has been associated with autoimmune disorders, diabetes mellitus, thyrotoxicosis, and hypopituitarism with adrenal insufficiency (George et al., 1984). Approximately 60% of patients with SPS have antibodies to glutamic acid decarboxylase (GAD2, or GAD65; 138275), the rate-limiting enzyme in the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), suggesting an immune-mediated pathogenesis (Folli et al., 1993). Approximately 10% of patients develop SPS as a paraneoplastic neurologic disorder associated with antibodies to amphiphysin (AMPH; 600418), an intracellular protein associated with neuronal synaptic vesicle endocytosis (Burns, 2005). See also congenital stiff-man syndrome, or hereditary hyperexplexia (149400), which is caused by mutations in subunits of the glycine receptor gene (GLRA1, 138491; GLRB, 138492). Meinck and Thompson (2002) provided a detailed review of stiff-person syndrome. They also discussed 2 possibly related conditions, progressive encephalomyelitis with rigidity (PERM), a more severe disorder with other neurologic features, and stiff-limb or stiff-leg syndrome, a focal disorder.
Hereditary coproporphyria
MedGen UID:
57931
Concept ID:
C0162531
Disease or Syndrome
Hereditary coproporphyria (HCP) is an acute (hepatic) porphyria in which the acute symptoms are neurovisceral and occur in discrete episodes. Attacks typically start in the abdomen with low-grade pain that slowly increases over a period of days (not hours) with nausea progressing to vomiting. In some individuals, the pain is predominantly in the back or extremities. When an acute attack is untreated, a motor neuropathy may develop over a period of days or a few weeks. The neuropathy first appears as weakness proximally in the arms and legs, then progresses distally to involve the hands and feet. Some individuals experience respiratory insufficiency due to loss of innervation of the diaphragm and muscles of respiration. Acute attacks are associated commonly with use of certain medications, caloric deprivation, and changes in female reproductive hormones. About 20% of those with an acute attack also experience photosensitivity associated with bullae and skin fragility.
Acute intermittent porphyria
MedGen UID:
56452
Concept ID:
C0162565
Disease or Syndrome
Acute intermittent porphyria (AIP), an autosomal dominant disorder, occurs in heterozygotes for an HMBS pathogenic variant that causes reduced activity of the enzyme porphobilinogen deaminase. AIP is considered "overt" in a heterozygote who was previously or is currently symptomatic; AIP is considered "latent" in a heterozygote who has never had symptoms, and typically has been identified during molecular genetic testing of at-risk family members. Note that GeneReviews does not use the term "carrier" for an individual who is heterozygous for an autosomal dominant pathogenic variant; GeneReviews reserves the term "carrier" for an individual who is heterozygous for an autosomal recessive disorder and thus is not expected to ever develop manifestations of the disorder. Overt AIP is characterized clinically by life-threatening acute neurovisceral attacks of severe abdominal pain without peritoneal signs, often accompanied by nausea, vomiting, tachycardia, and hypertension. Attacks may be complicated by neurologic findings (mental changes, convulsions, and peripheral neuropathy that may progress to respiratory paralysis), and hyponatremia. Acute attacks, which may be provoked by certain drugs, alcoholic beverages, endocrine factors, calorie restriction, stress, and infections, usually resolve within two weeks. Most individuals with AIP have one or a few attacks; about 3%-8% (mainly women) have recurrent attacks (defined as >3 attacks/year) that may persist for years. Other long-term complications are chronic renal failure, hepatocellular carcinoma (HCC), and hypertension. Attacks, which are very rare before puberty, are more common in women than men. Latent AIP. While all individuals heterozygous for an HMBS pathogenic variant that predisposes to AIP are at risk of developing overt AIP, most have latent AIP and never have symptoms.
Williams syndrome
MedGen UID:
59799
Concept ID:
C0175702
Disease or Syndrome
Williams syndrome (WS) is characterized by cardiovascular disease (elastin arteriopathy, peripheral pulmonary stenosis, supravalvar aortic stenosis, hypertension), distinctive facies, connective tissue abnormalities, intellectual disability (usually mild), a specific cognitive profile, unique personality characteristics, growth abnormalities, and endocrine abnormalities (hypercalcemia, hypercalciuria, hypothyroidism, and early puberty). Feeding difficulties often lead to poor weight gain in infancy. Hypotonia and hyperextensible joints can result in delayed attainment of motor milestones.
Succinate-semialdehyde dehydrogenase deficiency
MedGen UID:
124340
Concept ID:
C0268631
Disease or Syndrome
Succinic semialdehyde dehydrogenase (SSADH) deficiency is characterized by infantile-onset hypotonia, developmental delay, cognitive impairment, expressive language deficit, and mild ataxia. Epilepsy is present in about half of affected individuals and is more common in adults. Hyperkinetic behavior, aggression, self-injurious behaviors, hallucinations, and sleep disturbances have been reported in nearly half of all affected individuals, more commonly in those who are older. Basal ganglia signs including choreoathetosis, dystonia, and myoclonus have been reported in a few individuals with earlier-onset, more severe disease. Involvement beyond the central nervous system has not been described. Individuals with SSADH deficiency typically have 4-hydroxybutyric aciduria present on urine organic acid analysis. Head MRI reveals T2 hyperintensities in multiple regions, involving the globus pallidi, cerebellar dentate nuclei, subthalamic nuclei, subcortical white matter, and brain stem, as well as cerebral and sometimes cerebellar atrophy. EEG findings include background slowing and spike discharges that are usually generalized.
Chorea-acanthocytosis
MedGen UID:
98277
Concept ID:
C0393576
Disease or Syndrome
Chorea-acanthocytosis (ChAc) is characterized by a progressive movement disorder, cognitive and behavior changes, a myopathy that can be subclinical, and chronic hyperCKemia in serum. Although the disorder is named for acanthocytosis of the red blood cells, this feature is variable. The movement disorder is mostly limb chorea, but some individuals present with parkinsonism. Dystonia is common and affects the oral region and especially the tongue, causing dysarthria and serious dysphagia with resultant weight loss. Habitual tongue and lip biting are characteristic, as well as tongue protrusion dystonia. Progressive cognitive and behavioral changes resemble those in a frontal lobe syndrome. Seizures are observed in almost half of affected individuals and can be the initial manifestation. Myopathy results in progressive distal muscle wasting and weakness. Mean age of onset in ChAc is about 30 years, although ChAc can develop as early as the first decade or as late as the seventh decade. It runs a chronic progressive course and may lead to major disability within a few years. Life expectancy is reduced, with age of death ranging from 28 to 61 years.
Benign hereditary chorea
MedGen UID:
98278
Concept ID:
C0393584
Disease or Syndrome
NKX2-1-related disorders range from benign hereditary chorea (BHC) to choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress (also known as brain-lung-thyroid syndrome). Childhood-onset chorea, the hallmark of NKX2-1-related disorders, may or may not be associated with respiratory distress syndrome or congenital hypothyroidism. Chorea generally begins in early infancy or about age one year (most commonly) or in late childhood or adolescence, and progresses into the second decade after which it remains static or (rarely) remits. Pulmonary disease, the second most common manifestation, can include respiratory distress syndrome in neonates, interstitial lung disease in young children, and pulmonary fibrosis in older persons. The risk for pulmonary carcinoma is increased in young adults with an NKX2-1-related disorder. Thyroid dysfunction, the result of dysembryogenesis, can present as congenital hypothyroidism or compensated hypothyroidism. The risk for thyroid cancer is unknown and may not be increased. In one review, 50% of affected individuals had the full brain-lung-thyroid syndrome, 30% had involvement of brain and thyroid only, and 13% had isolated chorea only.
McLeod neuroacanthocytosis syndrome
MedGen UID:
140765
Concept ID:
C0398568
Disease or Syndrome
McLeod neuroacanthocytosis syndrome (designated as MLS throughout this review) is a multisystem disorder with central nervous system (CNS), neuromuscular, cardiovascular, and hematologic manifestations in males: CNS manifestations are a neurodegenerative basal ganglia disease including movement disorders, cognitive alterations, and psychiatric symptoms. Neuromuscular manifestations include a (mostly subclinical) sensorimotor axonopathy and muscle weakness or atrophy of different degrees. Cardiac manifestations include dilated cardiomyopathy, atrial fibrillation, and tachyarrhythmia. Hematologically, MLS is defined as a specific blood group phenotype (named after the first proband, Hugh McLeod) that results from absent expression of the Kx erythrocyte antigen and weakened expression of Kell blood group antigens. The hematologic manifestations are red blood cell acanthocytosis and compensated hemolysis. Alloantibodies in the Kell and Kx blood group system can cause strong reactions to transfusions of incompatible blood and severe anemia in affected male newborns of Kell-negative mothers. Females heterozygous for XK pathogenic variants have mosaicism for the Kell and Kx blood group antigens. Although they usually lack CNS and neuromuscular manifestations, some heterozygous females may develop clinical manifestations including chorea or late-onset cognitive decline.
Leukocyte adhesion deficiency type II
MedGen UID:
96022
Concept ID:
C0398739
Disease or Syndrome
Congenital disorder of glycosylation type IIc (CDG2C) is an autosomal recessive disorder characterized by moderate to severe psychomotor retardation, mild dysmorphism, and impaired neutrophil motility. It is a member of a group of disorders with a defect in the processing of protein-bound glycans. For a general overview of congenital disorders of glycosylation (CDGs), see CDG1A (212065) and CDG2A (212066). Frydman (1996) contended that the neutrophil defect in CDG2C, which has been referred to as 'leukocyte adhesion deficiency type II' (LAD2), is a manifestation of the disorder and that there are no cases of 'primary' LAD II. Etzioni and Harlan (1999) provided a comprehensive review of both leukocyte adhesion deficiency-1 (LAD1; 116920) and LAD2. While the functional neutrophil studies are similar in the 2 LADs, the clinical course is milder in LAD2. Furthermore, patients with LAD2 present other abnormal features, such as growth and mental retardation, which are related to the primary defect in fucose metabolism. Delayed separation of the umbilical cord occurs in LAD1. For a discussion of genetic heterogeneity of LAD, see 116920.
Inherited Creutzfeldt-Jakob disease
MedGen UID:
155837
Concept ID:
C0751254
Disease or Syndrome
Genetic prion disease generally manifests with cognitive difficulties, ataxia, and myoclonus (abrupt jerking movements of muscle groups and/or entire limbs). The order of appearance and/or predominance of these features and other associated neurologic and psychiatric findings vary. The three major phenotypes of genetic prion disease are genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann-Sträussler-Scheinker (GSS) syndrome. Although these phenotypes display overlapping clinical and pathologic features, recognition of these phenotypes can be useful when providing affected individuals and their families with information about the expected clinical course. The age at onset typically ranges from 50 to 60 years. The disease course ranges from a few months in gCJD and FFI to a few (up to 4, and in rare cases up to 10) years in GSS syndrome.
Neuronal ceroid lipofuscinosis 3
MedGen UID:
155549
Concept ID:
C0751383
Disease or Syndrome
The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). The hallmark of CLN3 is the ultrastructural pattern of lipopigment with a 'fingerprint' profile, which can have 3 different appearances: pure within a lysosomal residual body; in conjunction with curvilinear or rectilinear profiles; and as a small component within large membrane-bound lysosomal vacuoles. The combination of fingerprint profiles within lysosomal vacuoles is a regular feature of blood lymphocytes from patients with CLN3 (Mole et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (256730).
Primrose syndrome
MedGen UID:
162911
Concept ID:
C0796121
Disease or Syndrome
Primrose syndrome is characterized by macrocephaly, hypotonia, developmental delay, intellectual disability with expressive speech delay, behavioral issues, a recognizable facial phenotype, radiographic features, and altered glucose metabolism. Additional features seen in adults: sparse body hair, distal muscle wasting, and contractures. Characteristic craniofacial features include brachycephaly, high anterior hairline, deeply set eyes, ptosis, downslanted palpebral fissures, high palate with torus palatinus, broad jaw, and large ears with small or absent lobes. Radiographic features include calcification of the external ear cartilage, multiple Wormian bones, platybasia, bathrocephaly, slender bones with exaggerated metaphyseal flaring, mild epiphyseal dysplasia, and spondylar dysplasia. Additional features include hearing impairment, ocular anomalies, cryptorchidism, and nonspecific findings on brain MRI.
Renpenning syndrome
MedGen UID:
208670
Concept ID:
C0796135
Disease or Syndrome
Renpenning syndrome is an X-linked mental retardation syndrome with clinically recognizable features. Affected individuals have microcephaly, short stature, small testes, and dysmorphic facies, including tall narrow face, upslanting palpebral fissures, abnormal nasal configuration, cupped ears, and short philtrum. The nose may appear long or bulbous, with overhanging columella. Less consistent manifestations include ocular colobomas, cardiac malformations, cleft palate, and anal anomalies. Stevenson et al. (2005) proposed that the various X-linked mental retardation syndromes due to PQBP1 mutations be combined under the name of Renpenning syndrome.
Intellectual disability, X-linked 9
MedGen UID:
167112
Concept ID:
C0796215
Mental or Behavioral Dysfunction
X-linked intellectual developmental disorder-9 (XLID9) is characterized by moderately to severely impaired intellectual development. Some patients have also been reported with delayed motor development, seizures, and/or behavioral problems (Hamel et al., 1999; Froyen et al., 2007).
X-linked intellectual disability-short stature-overweight syndrome
MedGen UID:
901885
Concept ID:
C0796218
Disease or Syndrome
X-linked intellectual developmental disorder-12 (XLID12) is characterized by borderline to severe intellectual disability with variable neurologic features, short stature, and elevated body mass index (BMI) (Kumar et al., 2015).
Intellectual disability, X-linked 49
MedGen UID:
923000
Concept ID:
C0796221
Disease or Syndrome
CLCN4-related neurodevelopmental disorder (CLCN4-NDD), an X-linked disorder, is characterized in the 36 males reported to date by developmental delay or intellectual disability, behavioral/mental health issues (e.g., autism spectrum disorder, anxiety, hyperactivity, and bipolar disorder), epilepsy, and gastrointestinal dysfunction. The five heterozygous females with a de novo CLCN4 variant reported to date had findings very similar to those of affected males. Twenty-two of 25 heterozygous females identified in family studies following identification of an affected male were unaffected or had only mild specific learning difficulties and/or mental health concerns, whereas three were more severely affected.
Intellectual disability, X-linked 30
MedGen UID:
163235
Concept ID:
C0796237
Disease or Syndrome
Any non-syndromic X-linked intellectual disability in which the cause of the disease is a mutation in the PAK3 gene.
Migraine, familial hemiplegic, 1
MedGen UID:
331388
Concept ID:
C1832884
Disease or Syndrome
Familial hemiplegic migraine (FHM) falls within the category of migraine with aura. In migraine with aura (including FHM) the neurologic symptoms of aura are unequivocally localizable to the cerebral cortex or brain stem and include visual disturbance (most common), sensory loss (e.g., numbness or paresthesias of the face or an extremity), and dysphasia (difficulty with speech). FHM must include motor involvement, such as hemiparesis (weakness of an extremity). Hemiparesis occurs with at least one other symptom during FHM aura. Neurologic deficits with FHM attacks can be prolonged for hours to days and may outlast the associated migrainous headache. FHM is often earlier in onset than typical migraine, frequently beginning in the first or second decade; the frequency of attacks tends to decrease with age. Approximately 40%-50% of families with CACNA1A-FHM have cerebellar signs ranging from nystagmus to progressive, usually late-onset mild ataxia.
Myoclonic dystonia 11
MedGen UID:
331778
Concept ID:
C1834570
Disease or Syndrome
SGCE myoclonus-dystonia (SGCE-M-D) is a movement disorder characterized by a combination of rapid, brief muscle contractions (myoclonus) and/or sustained twisting and repetitive movements that result in abnormal postures (dystonia). The myoclonic jerks typical of SGCE-M-D most often affect the neck, trunk, and upper limbs with less common involvement of the legs. Approximately 50% of affected individuals have additional focal or segmental dystonia, presenting as cervical dystonia and/or writer's cramp. Non-motor features may include alcohol abuse, obsessive-compulsive disorder (OCD), and anxiety disorders. Symptom onset is usually in the first decade of life and almost always by age 20 years, but ranges from age six months to 80 years. Most affected adults report a dramatic reduction in myoclonus in response to alcohol ingestion. SGCE-M-D is compatible with an active life of normal span.
CARASIL syndrome
MedGen UID:
325051
Concept ID:
C1838577
Disease or Syndrome
HTRA1 disorder is a phenotypic spectrum in which some individuals have few to no symptoms and others manifest with the more severe CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy) phenotype. Those who have a heterozygous HTRA1 pathogenic variant may have mild neurologic findings (sometimes identified only on neuroimaging) or mild-to-moderate neurologic signs and symptoms of CARASIL. In this chapter, the term "classic CARASIL" refers to the more severe phenotype associated with biallelic pathogenic variants, and "HTRA1 cerebral small vessel disease" (HTRA1-CSVD) refers to the milder phenotype associated with a heterozygous HTRA1 pathogenic variant. Classic CARASIL is characterized by early-onset changes in the deep white matter of the brain observed on MRI, and associated neurologic findings. The most frequent initial symptom is gait disturbance from spasticity beginning between ages 20 and 40 years. Forty-four percent of affected individuals have stroke-like episodes before age 40 years. Mood changes (apathy and irritability), pseudobulbar palsy, and cognitive dysfunction begin between ages 20 and 50 years. The disease progresses slowly following the onset of neurologic symptoms. Scalp alopecia and acute mid- to lower-back pain (lumbago) before age 30 years are characteristic. The most frequent initial symptom in individuals with HTRA1-CSVD is slowly progressive gait disturbance after age 40 years, which may be followed by the development of mood changes and cognitive dysfunction. A majority of affected individuals have a stroke-like episode after age 40 years. Spondylosis and alopecia are seen in a minority of individuals with HTRA1-CSVD.
Fragile X-associated tremor/ataxia syndrome
MedGen UID:
333403
Concept ID:
C1839780
Disease or Syndrome
FMR1 disorders include fragile X syndrome (FXS), fragile X-associated tremor/ataxia syndrome (FXTAS), and fragile X-associated primary ovarian insufficiency (FXPOI). Fragile X syndrome occurs in individuals with an FMR1 full mutation or other loss-of-function variant and is nearly always characterized in affected males by developmental delay and intellectual disability along with a variety of behavioral issues. Autism spectrum disorder is present in 50%-70% of individuals with FXS. Affected males may have characteristic craniofacial features (which become more obvious with age) and medical problems including hypotonia, gastroesophageal reflux, strabismus, seizures, sleep disorders, joint laxity, pes planus, scoliosis, and recurrent otitis media. Adults may have mitral valve prolapse or aortic root dilatation. The physical and behavioral features seen in males with FXS have been reported in females heterozygous for the FMR1 full mutation, but with lower frequency and milder involvement. FXTAS occurs in individuals who have an FMR1 premutation and is characterized by late-onset, progressive cerebellar ataxia and intention tremor followed by cognitive impairment. Psychiatric disorders are common. Age of onset is typically between 60 and 65 years and is more common among males who are hemizygous for the premutation (40%) than among females who are heterozygous for the premutation (16%-20%). FXPOI, defined as hypergonadotropic hypogonadism before age 40 years, has been observed in 20% of women who carry a premutation allele compared to 1% in the general population.
Glucocorticoid resistance
MedGen UID:
333960
Concept ID:
C1841972
Disease or Syndrome
Generalized glucocorticoid resistance is an autosomal dominant disease characterized by increased plasma cortisol concentration and high urinary free cortisol, resistance to adrenal suppression by dexamethasone, and the absence of clinical stigmata of Cushing syndrome. The clinical expression of the disease is variable. Common features include hypoglycemia, hypertension, and metabolic alkalosis. In females, overproduction of adrenal androgens has been associated with infertility, male-pattern baldness, hirsutism, and menstrual irregularities. Other features include chronic fatigue and profound anxiety (summary by Chrousos et al., 1983; Donner et al., 2013).
Intellectual disability, X-linked 63
MedGen UID:
337002
Concept ID:
C1845672
Mental or Behavioral Dysfunction
Any non-syndromic X-linked intellectual disability in which the cause of the disease is a mutation in the ACSL4 gene.
Syndromic X-linked intellectual disability Lubs type
MedGen UID:
337496
Concept ID:
C1846058
Disease or Syndrome
MECP2 duplication syndrome is a severe neurodevelopmental disorder characterized by early-onset hypotonia, feeding difficulty, gastrointestinal manifestations including gastroesophageal reflux and constipation, delayed psychomotor development leading to severe intellectual disability, poor speech development, progressive spasticity, recurrent respiratory infections (in ~75% of affected individuals), and seizures (in ~50%). MECP2 duplication syndrome is 100% penetrant in males. Occasionally females have been described with a MECP2 duplication and a range of findings from mild intellectual disability to a phenotype similar to that seen in males. In addition to the core features, autistic behaviors, nonspecific neuroradiologic findings on brain MRI, mottled skin, and urogenital anomalies have been observed in several affected boys.
Huntington disease-like 2
MedGen UID:
341120
Concept ID:
C1847987
Disease or Syndrome
Huntington disease-like 2 (HDL2) typically presents in midlife with a relentless progressive triad of movement, emotional, and cognitive abnormalities which lead to death within ten to 20 years. HDL2 cannot be differentiated from Huntington disease clinically. Neurologic abnormalities include chorea, hypokinesia (rigidity, bradykinesia), dysarthria, and hyperreflexia in the later stages of the disease. There is a strong correlation between the duration of the disease and the progression of the motor and cognitive disorder.
Growth delay due to insulin-like growth factor I resistance
MedGen UID:
338622
Concept ID:
C1849157
Disease or Syndrome
Patients with mutations in the receptor for insulin-like growth factor I show intrauterine growth retardation and postnatal growth failure, resulting in short stature and microcephaly. Other features may include delayed bone age, developmental delay, and dysmorphic features.
Autosomal recessive early-onset Parkinson disease 7
MedGen UID:
344049
Concept ID:
C1853445
Disease or Syndrome
Parkinson's disease is a progressive disorder of the nervous system. The disorder affects several regions of the brain, especially an area called the substantia nigra that controls balance and movement.\n\nOften the first symptom of Parkinson's disease is trembling or shaking (tremor) of a limb, especially when the body is at rest. Typically, the tremor begins on one side of the body, usually in one hand. Tremors can also affect the arms, legs, feet, and face. Other characteristic symptoms of Parkinson's disease include rigidity or stiffness of the limbs and torso, slow movement (bradykinesia) or an inability to move (akinesia), and impaired balance and coordination (postural instability). These symptoms worsen slowly over time.\n\nParkinson's disease can also affect emotions and thinking ability (cognition). Some affected individuals develop psychiatric conditions such as depression and visual hallucinations. People with Parkinson's disease also have an increased risk of developing dementia, which is a decline in intellectual functions including judgment and memory.\n\nGenerally, Parkinson's disease that begins after age 50 is called late-onset disease. The condition is described as early-onset disease if signs and symptoms begin before age 50. Early-onset cases that begin before age 20 are sometimes referred to as juvenile-onset Parkinson's disease.
Autosomal recessive early-onset Parkinson disease 6
MedGen UID:
342982
Concept ID:
C1853833
Disease or Syndrome
PINK1 type of young-onset Parkinson disease is characterized by early onset (mean age 33 years) of tremor, bradykinesia, and rigidity that are often indistinguishable from other causes of Parkinson disease. Lower-limb dystonia may be a presenting sign. Postural instability, hyperreflexia, abnormal behavior, and psychiatric manifestations have been described. The disease is usually slowly progressive. Individuals have a marked and sustained response to oral administration of levodopa (L-dopa), frequently associated with L-dopa-induced fluctuations and dyskinesias.
ACTH-independent macronodular adrenal hyperplasia 1
MedGen UID:
347456
Concept ID:
C1857451
Disease or Syndrome
ACTH-independent macronodular adrenal hyperplasia (AIMAH) is an endogenous form of adrenal Cushing syndrome characterized by multiple bilateral adrenocortical nodules that cause a striking enlargement of the adrenal glands. Although some familial cases have been reported, the vast majority of AIMAH cases are sporadic. Patients typically present in the fifth or sixth decade of life, approximately 10 years later than most patients with other causes of Cushing syndrome (Swain et al., 1998; Christopoulos et al., 2005). Approximately 10 to 15% of adrenal Cushing syndrome is due to primary bilateral ACTH-independent adrenocortical pathology. The 2 main subtypes are AIMAH and primary pigmented nodular adrenocortical disease (PPNAD; see 610489), which is often a component of the Carney complex (160980) and associated with mutations in the PRKAR1A gene (188830). AIMAH is rare, representing less than 1% of endogenous causes of Cushing syndrome (Swain et al., 1998; Christopoulos et al., 2005). See also ACTH-independent Cushing syndrome (615830) due to somatic mutation in the PRKACA gene (601639). Cushing 'disease' (219090) is an ACTH-dependent disorder caused in most cases by pituitary adenomas that secrete excessive ACTH. Genetic Heterogeneity of ACTH-Independent Macronodular Adrenal Hyperplasia AIMAH2 (615954) is caused by germline mutation on 1 allele of the ARMC5 gene (615549) coupled with a somatic mutation in the other allele.
7q11.23 microduplication syndrome
MedGen UID:
347562
Concept ID:
C1857844
Disease or Syndrome
7q11.23 duplication syndrome is characterized by delayed motor, speech, and social skills in early childhood; neurologic abnormalities (hypotonia, adventitious movements, and abnormal gait and station); speech sound disorders including motor speech disorders (childhood apraxia of speech and/or dysarthria) and phonologic disorders; behavior problems including anxiety disorders (especially social anxiety disorder [social phobia]), selective mutism, attention-deficit/hyperactivity disorder, oppositional disorders, physical aggression, and autism spectrum disorder; and intellectual disability in some individuals. Distinctive facial features are common. Cardiovascular disease includes dilatation of the ascending aorta. Approximately 30% of individuals have one or more congenital anomalies.
Spinocerebellar ataxia type 12
MedGen UID:
347653
Concept ID:
C1858501
Disease or Syndrome
Rare disease with manifestations of action tremor associated with relatively mild cerebellar ataxia. Associated pyramidal and extrapyramidal signs and dementia have been reported. Prevalence is unknown. Approximately 40 families have been reported. The pathogenesis seems to be related to a toxic effect at the RNA level as it is caused by a CAG expansion at the 5'' end of the PPP2R2B gene on chromosome 5q31-5q32.
Celiac disease, susceptibility to, 1
MedGen UID:
395227
Concept ID:
C1859310
Finding
Celiac disease is a systemic autoimmune disease that can be associated with gastrointestinal findings (diarrhea, malabsorption, abdominal pain and distension, bloating, vomiting, and weight loss) and/or highly variable non-gastrointestinal findings (dermatitis herpetiformis, chronic fatigue, joint pain/inflammation, iron deficiency anemia, migraines, depression, attention-deficit disorder, epilepsy, osteoporosis/osteopenia, infertility and/or recurrent fetal loss, vitamin deficiencies, short stature, failure to thrive, delayed puberty, dental enamel defects, and autoimmune disorders). Classic celiac disease, characterized by mild to severe gastrointestinal symptoms, is less common than non-classic celiac disease, characterized by absence of gastrointestinal symptoms.
Hereditary geniospasm
MedGen UID:
348757
Concept ID:
C1860972
Finding
Geniospasm is characterized by spontaneous intermittent involuntary quivering or trembling of the chin that is intensified by stress or anxiety. The movements are first noticed in infancy or childhood and usually abate by late adulthood (Wadlington, 1958; Danek et al., 1991).
Huntington disease-like 1
MedGen UID:
355137
Concept ID:
C1864112
Disease or Syndrome
Genetic prion disease generally manifests with cognitive difficulties, ataxia, and myoclonus (abrupt jerking movements of muscle groups and/or entire limbs). The order of appearance and/or predominance of these features and other associated neurologic and psychiatric findings vary. The three major phenotypes of genetic prion disease are genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann-Sträussler-Scheinker (GSS) syndrome. Although these phenotypes display overlapping clinical and pathologic features, recognition of these phenotypes can be useful when providing affected individuals and their families with information about the expected clinical course. The age at onset typically ranges from 50 to 60 years. The disease course ranges from a few months in gCJD and FFI to a few (up to 4, and in rare cases up to 10) years in GSS syndrome.
Pigmented nodular adrenocortical disease, primary, 1
MedGen UID:
400627
Concept ID:
C1864846
Disease or Syndrome
Primary pigmented nodular adrenocortical disease (PPNAD) is a form of ACTH-independent adrenal hyperplasia resulting in Cushing syndrome. It is usually seen as a manifestation of the Carney complex (CNC1; 160980), a multiple neoplasia syndrome. However, PPNAD can also occur in isolation (Groussin et al., 2002). Genetic Heterogeneity of Primary Pigmented Nodular Adrenocortical Disease See also PPNAD2 (610475), caused by mutation in the PDE11A gene (604961) on chromosome 2q31; PPNAD3 (614190), caused by mutation in the PDE8B gene (603390) on chromosome 5q13; and PPNAD4 (615830), caused by a duplication on chromosome 19p13 that includes the PRKACA gene (601639).
Pigmented nodular adrenocortical disease, primary, 2
MedGen UID:
355843
Concept ID:
C1864851
Disease or Syndrome
Any primary pigmented nodular adrenocortical disease in which the cause of the disease is a mutation in the PDE11A gene.
Koolen-de Vries syndrome
MedGen UID:
355853
Concept ID:
C1864871
Disease or Syndrome
Koolen-de Vries syndrome (KdVS) is characterized by developmental delay / intellectual disability, neonatal/childhood hypotonia, dysmorphisms, congenital malformations, and behavioral features. Psychomotor developmental delay is noted in all individuals from an early age. The majority of individuals with KdVS function in the mild-to-moderate range of intellectual disability. Other findings include speech and language delay (100%), epilepsy (~33%), congenital heart defects (25%-50%), renal and urologic anomalies (25%-50%), and cryptorchidism (71% of males). Behavior in most is described as friendly, amiable, and cooperative.
Perry syndrome
MedGen UID:
357007
Concept ID:
C1868594
Disease or Syndrome
The spectrum of DCTN1-related neurodegeneration includes Perry syndrome, distal hereditary motor neuronopathy type 7B (dHMN7B), frontotemporal dementia (FTD), motor neuron disease / amyotrophic lateral sclerosis (ALS), and progressive supranuclear palsy. Some individuals present with overlapping phenotypes (e.g., FTD-ALS, Perry syndrome-dHMN7B). Perry syndrome (the most common of the phenotypes associated with DCTN1) is characterized by parkinsonism, neuropsychiatric symptoms, hypoventilation, and weight loss. The mean age of onset in those with Perry syndrome is 49 years (range: 35-70 years), and the mean disease duration is five years (range: 2-14 years). In most affected persons, the reported cause/circumstance of death relates to sudden death/hypoventilation or suicide.
Panic disorder 1
MedGen UID:
401493
Concept ID:
C1868649
Mental or Behavioral Dysfunction
The DSM-IV (American Psychiatric Association, 1994) defines panic disorder as the spontaneous, unexpected occurrence of panic attacks followed by persistent concern, worry, and anxiety about having additional panic attacks. Panic attacks are defined as a discrete period of intense fear or discomfort in which at least 4 of 13 symptom criteria are met that develop abruptly and reach a peak within 10 minutes. Some of these criteria include cardiac palpitations, sweating, feelings of choking, fear of losing control, and fear of dying. Panic disorder is divided into panic disorder with or without accompanying agoraphobia. However, agoraphobia can also occur without panic disorder, and panic attacks can occur in the absence of panic disorder. Comorbidity with depressive and addictive disorders is frequent. Barlow et al. (1994) and Smoller and Tsuang (1998) noted that because the diagnostic criteria remain purely clinical, the nosology of anxiety disorders, such as panic disorder, is controversial and evolving. Therefore, it is difficult to do genetic studies because of the difficulty in delineating overlapping phenotypes within the broader context of anxiety disorders. For example, there may be overlap of panic with specific phobias, variable expressivity of panic and anxiety or depression, or phenocopies within a family. The terms 'anxiety neurosis' and 'phobic neurosis' were used in the past (before the DSM-III in 1980) to encompass all of these disorders. Smoller and Tsuang (1998) suggested that dimensional personality traits, such as shyness, behavioral inhibition, and neuroticism (see 607834), could be used to define an anxiety phenotype. Schumacher et al. (2011) provided a review of the genetics of panic disorder. They noted that there is high (80%) comorbidity with other psychiatric disorders, including agoraphobia, mood disorders, substance abuse, and other anxiety disorders. Associated personality traits include anxiety sensitivity, behavioral inhibition, neuroticism, and harm avoidance. Women are more susceptible to development of the disorder, which has an average age of onset at 23.6 years. Genetic Heterogeneity of Susceptibility to Panic Disorder Susceptibility to panic disorder-1 (PAND1) has been mapped to chromosome 13q. See also PAND2 (607853), mapped to chromosome 9, and PAND3 (609985), mapped to chromosome 4.
Dystonia 12
MedGen UID:
358384
Concept ID:
C1868681
Disease or Syndrome
ATP1A3-related neurologic disorders represent a clinical continuum in which at least three distinct phenotypes have been delineated: rapid-onset dystonia-parkinsonism (RDP); alternating hemiplegia of childhood (ACH); and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS). However, some affected individuals have intermediate phenotypes or only a few features that do not fit well into one of these major phenotypes. RDP has been characterized by: abrupt onset of dystonia over days to weeks with parkinsonism (primarily bradykinesia and postural instability); common bulbar involvement; and absence or minimal response to an adequate trial of L-dopa therapy, with few exceptions. Often fever, physiologic stress, or alcoholic binges trigger the onset of symptoms. After their initial appearance, symptoms often stabilize with little improvement; occasionally second episodes occur with abrupt worsening of symptoms. Rarely, affected individuals have reported a more gradual onset of symptoms over weeks to months. Anxiety, depression, and seizures have been reported. Age of onset ranges from four to 55 years, although a childhood variation of RDP with onset between ages nine and 14 months has been reported. AHC is a complex neurodevelopmental syndrome most frequently manifesting in infancy or early childhood with paroxysmal episodic neurologic dysfunction including alternating hemiparesis or dystonia, quadriparesis, seizure-like episodes, and oculomotor abnormalities. Episodes can last for minutes, hours, days, or even weeks. Remission of symptoms occurs with sleep and immediately after awakening. Over time, persistent neurologic deficits including oculomotor apraxia, ataxia, choreoathetosis, dystonia, parkinsonism, and cognitive and behavioral dysfunction develop in the majority of those affected; more than 50% develop epilepsy in addition to their episodic movement disorder phenotype. CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) syndrome is characterized by episodes of ataxic encephalopathy and/or weakness during and after a febrile illness. Onset is between ages six months and four years. Some acute symptoms resolve; progression of sensory losses and severity vary.
Intellectual disability, autosomal dominant 1
MedGen UID:
409857
Concept ID:
C1969562
Mental or Behavioral Dysfunction
MBD5 haploinsufficiency is a neurodevelopmental disorder characterized by developmental delay, intellectual disability, severe speech impairment, seizures, sleep disturbances, and abnormal behaviors. Most children lack speech entirely or have single words, short phrases, or short sentences. Seizures are present in more than 80% of children; onset is usually around age two years. Sleep disturbances, present in about 90%, can result in excessive daytime drowsiness. Abnormal behaviors can include autistic-like behaviors (80%) and self-injury and aggression (>60%).
Chromosome 3q29 microdeletion syndrome
MedGen UID:
393265
Concept ID:
C2674949
Disease or Syndrome
3q29 recurrent deletion is characterized by neurodevelopmental and/or psychiatric manifestations including mild-to-moderate intellectual disability (ID), autism spectrum disorder (ASD), anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), executive function deficits, graphomotor weakness, and psychosis/schizophrenia. Age at onset for psychosis or prodrome can be younger than the typical age at onset in the general population. Neurodevelopmental and psychiatric conditions are responsible for the majority of the disability associated with the 3q29 deletion. Other common findings are failure to thrive and feeding problems in infancy that persist into childhood, gastrointestinal disorders (including constipation and gastroesophageal reflux disease [GERD]), ocular issues, dental anomalies, and congenital heart defects (especially patent ductus arteriosus). Structural anomalies of the posterior fossa may be seen on neuroimaging. To date more than 200 affected individuals have been identified.
Wilms tumor, aniridia, genitourinary anomalies, intellectual disability, and obesity syndrome
MedGen UID:
382718
Concept ID:
C2675904
Disease or Syndrome
For a detailed discussion of the WAGR syndrome, see 194072. In a subgroup of individuals with the WAGR syndrome, obesity develops. The phenotype in this subset is associated with haploinsufficiency for the BDNF gene.
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5
MedGen UID:
413981
Concept ID:
C2751319
Disease or Syndrome
Four phenotypes comprise the RRM2B mitochondrial DNA maintenance defects (RRM2B-MDMDs): RRM2B encephalomyopathic MDMD, the most severe phenotype, usually manifesting shortly after birth as hypotonia, poor feeding, and faltering growth requiring hospitalization. Subsequent assessments are likely to reveal multisystem involvement including sensorineural hearing loss, renal tubulopathy, and respiratory failure. Autosomal dominant progressive external ophthalmoplegia (adPEO), typically adult onset; other manifestations can include ptosis, bulbar dysfunction, fatigue, and muscle weakness. RRM2B autosomal recessive progressive external ophthalmoplegia (arPEO), a typically childhood-onset predominantly myopathic phenotype of PEO, ptosis, proximal muscle weakness, and bulbar dysfunction. RRM2B mitochondrial neurogastrointestinal encephalopathy (MNGIE)-like, characterized by progressive ptosis, ophthalmoplegia, gastrointestinal dysmotility, cachexia, and peripheral neuropathy. To date, 78 individuals from 52 families with a molecularly confirmed RRM2B-MDMD have been reported.
Familial amyloid neuropathy
MedGen UID:
414031
Concept ID:
C2751492
Disease or Syndrome
Hereditary transthyretin (ATTR) amyloidosis is characterized by a slowly progressive peripheral sensorimotor and/or autonomic neuropathy as well as non-neuropathic changes of cardiomyopathy, nephropathy, vitreous opacities, and CNS amyloidosis. The disease usually begins in the third to fifth decade in persons from endemic foci in Portugal and Japan; onset is later in persons from other areas. Typically, sensory neuropathy starts in the lower extremities with paresthesias and hypesthesias of the feet, followed within a few years by motor neuropathy. In some persons, particularly those with early-onset disease, autonomic neuropathy is the first manifestation of the condition; findings can include: orthostatic hypotension, constipation alternating with diarrhea, attacks of nausea and vomiting, delayed gastric emptying, sexual impotence, anhidrosis, and urinary retention or incontinence. Cardiac amyloidosis is mainly characterized by progressive cardiomyopathy. Individuals with leptomeningeal amyloidosis may have the following CNS findings: dementia, psychosis, visual impairment, headache, seizures, motor paresis, ataxia, myelopathy, hydrocephalus, or intracranial hemorrhage.
Clark-Baraitser syndrome
MedGen UID:
443983
Concept ID:
C2931130
Disease or Syndrome
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by intellectual disability, obesity, macrocephaly, behavioral abnormalities (such as aggressive tantrums and autistic-like behavior), and delayed speech development. Dysmorphic facial features include large, square forehead, prominent supraorbital ridges, broad nasal tip, large ears, prominent lower lip, and minor dental anomalies such as small upper lateral incisors and central incisor gap.
Chromosome 15q11.2 deletion syndrome
MedGen UID:
467404
Concept ID:
C3180937
Disease or Syndrome
A heterozygous deletion of chromosome 15q11.2 may increase the susceptibility to neuropsychiatric or neurodevelopmental problems, including delayed psychomotor development, speech delay, autism spectrum disorder, attention deficit-hyperactivity disorder, obsessive-compulsive disorder, and possibly seizures (summary by Doornbos et al., 2009 and Burnside et al., 2011). See also chromosome 15q11.2 duplication syndrome (608636).
Wolfram-like syndrome
MedGen UID:
481988
Concept ID:
C3280358
Disease or Syndrome
Autosomal dominant Wolfram-like syndrome (WFSL) is characterized by the clinical triad of congenital progressive hearing impairment, diabetes mellitus, and optic atrophy. The hearing impairment, which is usually diagnosed in the first decade of life, is relatively constant and alters mainly low- and middle-frequency ranges (summary by Valero et al., 2008). Wolfram syndrome (WFS1; 222300) is an autosomal recessive allelic disorder characterized by optic atrophy, diabetes mellitus, hearing loss, and diabetes insipidus, and is caused by homozygous or compound heterozygous mutation in the WFS1 gene. An autosomal dominant syndrome involving optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy (125250), is caused by heterozygous mutation in the OPA1 gene (605290).
Intellectual disability, autosomal recessive 25
MedGen UID:
482174
Concept ID:
C3280544
Mental or Behavioral Dysfunction
Neurodegeneration with brain iron accumulation 5
MedGen UID:
763887
Concept ID:
C3550973
Disease or Syndrome
Beta-propeller protein-associated neurodegeneration (BPAN) is typically characterized by early-onset seizures, infantile-onset developmental delay, intellectual disability, absent-to-limited expressive language, motor dysfunction (ataxia), and abnormal behaviors often similar to autism spectrum disorder. Seizure types including generalized (absence, tonic, atonic, tonic-clonic and myoclonic), focal with impaired consciousness, and epileptic spasms, as well as epileptic syndromes (West syndrome and Lennox-Gastaut syndrome) can be seen. With age seizures tend to resolve or become less prominent, whereas cognitive decline and movement disorders (progressive parkinsonism and dystonia) emerge as characteristic findings.
Malan overgrowth syndrome
MedGen UID:
766574
Concept ID:
C3553660
Disease or Syndrome
Malan syndrome (MALNS) is clinically characterized by overgrowth, advanced bone age, macrocephaly, and dysmorphic facial features. Patients develop marfanoid habitus, with long and slender body, very low body mass, long narrow face, and arachnodactyly, with age. Impaired intellectual development and behavior anomalies are present (summary by Martinez et al., 2015).
Intellectual developmental disorder with autism and macrocephaly
MedGen UID:
767287
Concept ID:
C3554373
Disease or Syndrome
CHD8-related neurodevelopmental disorder with overgrowth (CHD8-NDD) is characterized by generalized overgrowth, developmental delay / intellectual disability (DD/ID), autism spectrum disorder (ASD), neuropsychiatric issues, neurologic problems, sleep disturbance, and gastrointestinal issues The most common findings are the development of macrocephaly (most often during infancy) and tall stature (most typically during puberty), which is often accompanied by ASD and/or DD/ID. Most, if not all, affected individuals have some degree of DD, most commonly speech and motor delays. When present, ID is most often in the mild-to-moderate range. Sleep disturbance is characterized by difficulty with both initiation (delayed sleep onset) and maintenance (frequent night awakenings) of sleep. The most common gastrointestinal issue is constipation with or without periods of diarrhea. Less common features are hypotonia (about 30% of affected individuals), seizures (10%-15%), dystonia (rare), and Chiari I malformation (rare).
Microcephalic primordial dwarfism, Alazami type
MedGen UID:
767353
Concept ID:
C3554439
Disease or Syndrome
Alazami syndrome is an autosomal recessive disorder characterized by severe growth restriction present at birth, severely impaired intellectual development, and distinctive facial features. Some patients have been reported with skeletal and behavioral features (summary by Imbert-Bouteille et al., 2019).
Mitochondrial complex III deficiency nuclear type 2
MedGen UID:
767519
Concept ID:
C3554605
Disease or Syndrome
Mitochondrial complex III deficiency nuclear type 2 is an autosomal recessive severe neurodegenerative disorder that usually presents in childhood, but may show later onset, even in adulthood. Affected individuals have motor disability, with ataxia, apraxia, dystonia, and dysarthria, associated with necrotic lesions throughout the brain. Most patients also have cognitive impairment and axonal neuropathy and become severely disabled later in life (summary by Ghezzi et al., 2011). The disorder may present clinically as spinocerebellar ataxia or Leigh syndrome, or with psychiatric disturbances (Morino et al., 2014; Atwal, 2014; Nogueira et al., 2013). For a discussion of genetic heterogeneity of mitochondrial complex III deficiency, see MC3DN1 (124000).
X-linked intellectual disability, Cantagrel type
MedGen UID:
813060
Concept ID:
C3806730
Disease or Syndrome
X-linked intellectual developmental disorder-98 (XLID98) is a neurodevelopmental disorder characterized by delayed psychomotor development, poor speech, behavioral abnormalities, poor overall growth, dysmorphic facial features, and often early-onset seizures. Some carrier females are unaffected, whereas other females with mutations are affected; males tend to be more severely affected than females. It is believed that the phenotypic variability and disease manifestations in female carriers results from skewed X-inactivation or cellular mosaicism (summary by de Lange et al., 2016).
Basal ganglia calcification, idiopathic, 5
MedGen UID:
815975
Concept ID:
C3809645
Disease or Syndrome
Primary familial brain calcification (PFBC) is a neurodegenerative disorder with characteristic calcium deposits in the basal ganglia and other brain areas visualized on neuroimaging. Most affected individuals are in good health during childhood and young adulthood and typically present in the fourth to fifth decade with a gradually progressive movement disorder and neuropsychiatric symptoms. The movement disorder first manifests as clumsiness, fatigability, unsteady gait, slow or slurred speech, dysphagia, involuntary movements, or muscle cramping. Neuropsychiatric symptoms, often the first or most prominent manifestations, range from mild difficulty with concentration and memory to changes in personality and/or behavior, to psychosis and dementia. Seizures of various types occur frequently, some individuals experience chronic headache and vertigo; urinary urgency or incontinence may be present.
Macrocephaly-developmental delay syndrome
MedGen UID:
816555
Concept ID:
C3810225
Mental or Behavioral Dysfunction
Autosomal recessive intellectual developmental disorder-41 (MRT41) is characterized by macrocephaly and global developmental delay. Some patients have seizures (Baple et al., 2014).
Intellectual disability-severe speech delay-mild dysmorphism syndrome
MedGen UID:
862201
Concept ID:
C4013764
Mental or Behavioral Dysfunction
Intellectual developmental disorder with language impairment and with or without autistic features is a neurodevelopmental disorder characterized by global developmental delay with moderate to severe speech delay that particularly affects expressive speech. Most patients have articulation defects, but frank verbal dyspraxia is not observed. Common dysmorphic features include broad forehead, downslanting palpebral fissures, short nose with broad tip, relative macrocephaly, frontal hair upsweep, and prominent digit pads. Gross motor skills are also delayed. Some patients have autistic features and/or behavioral problems. All reported cases have occurred de novo (review by Le Fevre et al., 2013).
ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder
MedGen UID:
862975
Concept ID:
C4014538
Disease or Syndrome
ADNP-related disorder is characterized by hypotonia, severe speech and motor delay, mild-to-severe intellectual disability, and characteristic facial features (prominent forehead, high anterior hairline, wide and depressed nasal bridge, and short nose with full, upturned nasal tip) based on a cohort of 78 individuals. Features of autism spectrum disorder are common (stereotypic behavior, impaired social interaction). Other common findings include additional behavioral problems, sleep disturbance, brain abnormalities, seizures, feeding issues, gastrointestinal problems, visual dysfunction (hypermetropia, strabismus, cortical visual impairment), musculoskeletal anomalies, endocrine issues including short stature and hormonal deficiencies, cardiac and urinary tract anomalies, and hearing loss.
Intellectual disability, autosomal dominant 29
MedGen UID:
863578
Concept ID:
C4015141
Mental or Behavioral Dysfunction
SETBP1 haploinsufficiency disorder (SETBP1-HD) is characterized by hypotonia and mild motor developmental delay; intellectual abilities ranging from normal to severe disability; speech and language disorder; behavioral problems (most commonly attention/concentration deficits and hyperactivity, impulsivity), and refractive errors and strabismus. Typically children with SETBP1-HD whose intellect is in the normal or borderline range (IQ 80-90) were diagnosed following genetic testing for behavioral problems and/or severe speech and language disorders (respectively: the inability to produce sounds in words correctly, and deficits in the understanding and/or expression of words and sentences). To date, 47 individuals with SETBP1-HD have been reported.
Tenorio syndrome
MedGen UID:
864147
Concept ID:
C4015710
Disease or Syndrome
Tenorio syndrome (TNORS) is characterized by overgrowth, macrocephaly, and impaired intellectual development. Some patients may have mild hydrocephaly, hypoglycemia, and inflammatory diseases resembling Sjogren syndrome (270150) (summary by Tenorio et al., 2014).
Luscan-Lumish syndrome
MedGen UID:
898669
Concept ID:
C4085873
Disease or Syndrome
Luscan-Lumish syndrome (LLS) is characterized by macrocephaly, intellectual disability, speech delay, low sociability, and behavioral problems. More variable features include postnatal overgrowth, obesity, advanced carpal ossification, developmental delay, and seizures (Luscan et al., 2014; Lumish et al., 2015)
Lamb-Shaffer syndrome
MedGen UID:
903542
Concept ID:
C4225202
Disease or Syndrome
Lamb-Shaffer syndrome is a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, poor expressive speech, and mild dysmorphic facial features. Additional variable skeletal abnormalities may also be present (summary by Nesbitt et al., 2015).
Skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome
MedGen UID:
896409
Concept ID:
C4225270
Disease or Syndrome
Kosaki overgrowth syndrome (KOGS) is characterized by a facial gestalt involving prominent forehead, proptosis, downslanting palpebral fissures, broad nasal bridge, thin upper lip, and pointed chin. Affected individuals are tall, with an elongated lower segment, and have large hands and feet. Skin is hyperelastic and fragile. Patients exhibit progressive dilatory and vascular changes in basilar/vertebral and coronary arteries starting in the teenage years (Takenouchi et al., 2015; Takenouchi et al., 2021).
Myoclonic dystonia 26
MedGen UID:
904244
Concept ID:
C4225341
Disease or Syndrome
Myoclonic dystonia-26 (DYT26) is an autosomal dominant neurologic disorder characterized by onset of myoclonic jerks affecting the upper limbs in the first or second decade of life. The disorder is progressive, and patients later develop dystonia with predominant involvement of the craniocervical regions and sometimes the trunk and/or lower limbs. Dystonia dominates the clinical picture (summary by Mencacci et al., 2015).
Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome
MedGen UID:
897984
Concept ID:
C4225351
Disease or Syndrome
White-Sutton syndrome is a neurodevelopmental disorder characterized by a wide spectrum of cognitive dysfunction, developmental delays (particularly in speech and language acquisition), hypotonia, autism spectrum disorder, and other behavioral problems. Additional features commonly reported include seizures, refractive errors and strabismus, hearing loss, sleep disturbance (particularly sleep apnea), feeding and gastrointestinal problems, mild genital abnormalities in males, and urinary tract involvement in both males and females.
Intellectual disability, X-linked, syndromic 33
MedGen UID:
895979
Concept ID:
C4225418
Disease or Syndrome
X-linked syndromic intellectual developmental disorder-33 (MRXS33) is an X-linked recessive neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, and characteristic facial features (summary by O'Rawe et al., 2015).
Intellectual disability, X-linked 61
MedGen UID:
924419
Concept ID:
C4283894
Disease or Syndrome
Tonne-Kalscheuer syndrome (TOKAS) is an X-linked recessive multiple congenital anomaly disorder with 2 main presentations. Most patients exhibit global developmental delay apparent from early infancy, impaired intellectual development, speech delay, behavioral abnormalities, and abnormal gait. Affected individuals also have dysmorphic facial features that evolve with age, anomalies of the hands, feet, and nails, and urogenital abnormalities with hypogenitalism. A subset of more severely affected males develop congenital diaphragmatic hernia in utero, which may result in perinatal or premature death. Carrier females may have very mild skeletal or hormonal abnormalities (summary by Frints et al., 2019). Also see Fryns syndrome (229850), an autosomal recessive disorder with overlapping features.
Developmental and epileptic encephalopathy, 49
MedGen UID:
934602
Concept ID:
C4310635
Disease or Syndrome
Developmental and epileptic encephalopathy-49 (DEE49) is a severe autosomal recessive neurologic disorder characterized by onset of seizures in the neonatal period, global developmental delay with intellectual disability and lack of speech, hypotonia, spasticity, and coarse facial features. Some patients may have brain calcifications on imaging (summary by Han et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Intellectual disability, autosomal dominant 43
MedGen UID:
934738
Concept ID:
C4310771
Mental or Behavioral Dysfunction
HIVEP2-related intellectual disability is a neurological disorder characterized by moderate to severe developmental delay and intellectual disability and mild physical abnormalities (dysmorphic features). Early symptoms of the condition include weak muscle tone (hypotonia) and delayed development of motor skills, such as sitting, standing, and walking. After learning to walk, many affected individuals continue to have difficulty with this activity; their walking style (gait) is often unbalanced and wide-based. Speech is also delayed, and some people with this condition never learn to talk. Most people with HIVEP2-related intellectual disability also have unusual physical features, such as widely spaced eyes (hypertelorism), a broad nasal bridge, or fingers with tapered ends, although there is no characteristic pattern of such features among affected individuals. Many people with the condition exhibit neurodevelopmental disorders, such as hyperactivity, attention deficit disorder, aggression, anxiety, and autism spectrum disorder, which is a group of developmental disorders characterized by impaired communication and social interaction.\n\nOther features of HIVEP2-related intellectual disability include mild abnormalities in the structure of the brain and an abnormally small brain and head size (microcephaly). Less common health problems include seizures; recurrent ear infections; and eye disorders, such as eyes that do not look in the same direction (strabismus), "lazy eye" (amblyopia), and farsightedness (hyperopia). Some people with HIVEP2-related intellectual disability have gastrointestinal problems, which can include backflow of acidic stomach contents into the esophagus (gastroesophageal reflux) and constipation.
Intellectual disability, autosomal dominant 42
MedGen UID:
934741
Concept ID:
C4310774
Mental or Behavioral Dysfunction
GNB1 encephalopathy (GNB1-E) is characterized by moderate-to-severe developmental delay / intellectual disability, structural brain abnormalities, and often infantile hypotonia and seizures. Other less common findings include dystonia, reduced vision, behavior issues, growth delay, gastrointestinal (GI) problems, genitourinary (GU) abnormalities in males, and cutaneous mastocytosis.
SIN3A-related intellectual disability syndrome due to a point mutation
MedGen UID:
934771
Concept ID:
C4310804
Disease or Syndrome
Witteveen-Kolk syndrome (WITKOS) is an autosomal dominant disorder with characteristic distinctive facial features, microcephaly, short stature, and mildly impaired intellectual development with delayed cognitive and motor development and subtle anomalies on MRI-brain imaging (summary by Balasubramanian et al., 2021).
Intellectual disability, X-linked, syndromic, Bain type
MedGen UID:
934781
Concept ID:
C4310814
Disease or Syndrome
Most individuals with HNRNPH2-related neurodevelopmental disorder (HNRNPH2-NDD) have symptoms early in life, before age 12 months. The major features of HNRNPH2-NDD are developmental delay / intellectual disability, motor and language delays, behavioral and psychiatric disorders, and growth and musculoskeletal abnormalities. Minor features include dysmorphic facies, gastrointestinal disturbances, epilepsy, and visual defects. Although HNRNPH2-NDD is an X-linked condition, there is not enough information on affected females versus affected males to make any generalizations about phenotypic differences between the two sexes.
Xq25 microduplication syndrome
MedGen UID:
935016
Concept ID:
C4311049
Disease or Syndrome
Xq25 duplication syndrome is an X-linked neurodevelopmental disorder characterized by delayed development and intellectual disability associated with abnormal behavior and dysmorphic facial features. Additional variable features may include thin corpus callosum on brain imaging and sleep disturbances. Carrier females may be mildly affected (summary by Leroy et al., 2016).
Intellectual developmental disorder with gastrointestinal difficulties and high pain threshold
MedGen UID:
1385744
Concept ID:
C4479517
Disease or Syndrome
Jansen-de Vries syndrome (JDVS) is an autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability with speech delay, and behavioral abnormalities. Most patients have variable additional features, including feeding and gastrointestinal difficulties, high pain threshold and/or hypersensitivity to sound, and dysmorphic features, including mild facial abnormalities, strabismus, and small hands and feet (summary by Jansen et al., 2017).
Noonan syndrome-like disorder with loose anagen hair 2
MedGen UID:
1376945
Concept ID:
C4479577
Disease or Syndrome
An inherited condition caused by autosomal dominant mutation(s) in the PPP1CB gene, encoding serine/threonine-protein phosphatase PP1-beta catalytic subunit. The condition is characterized by facial features similar to those seen in Noonan syndrome but may also include short stature, cognitive deficits, relative macrocephaly, small posterior fossa resulting in Chiari I malformation, hypernasal voice, cardiac defects, and ectodermal abnormalities, which typically presents as slow-growing, sparse, and/or unruly hair.
Intellectual developmental disorder with neuropsychiatric features
MedGen UID:
1379216
Concept ID:
C4479636
Disease or Syndrome
Intellectual developmental disorder with neuropsychiatric features is an autosomal recessive disorder characterized by moderate intellectual disability, relatively mild seizures, and neuropsychiatric abnormalities, such as anxiety, obsessive-compulsive behavior, and autistic features. Mild facial dysmorphic features may also be present (summary by Srour et al., 2017).
Rahman syndrome
MedGen UID:
1388282
Concept ID:
C4479637
Disease or Syndrome
The name HIST1H1E syndrome has been proposed as a mnemonic for the characteristic features of this emerging, recognizable phenotype: hypotonia; intellectual disability with behavioral issues; skeletal; testes (undescended) and thyroid; heart anomalies (most commonly atrial septal defect); and ectodermal issues (including sparse hair, thin nails, and abnormal dentition). In the 47 affected individuals reported to date, predominant findings were intellectual disability (ranging from mild to profound) and behavioral problems (combinations of anxiety/phobias, obsessive behaviors, attention-deficit/hyperactivity disorder, and autistic spectrum disorder/traits among others). Skeletal involvement can include scoliosis and decreased bone mineral density. Other findings in some include seizures, craniosynostosis, and hearing loss. Life expectancy does not appear to be reduced in HIST1H1E syndrome.
Gabriele de Vries syndrome
MedGen UID:
1375401
Concept ID:
C4479652
Disease or Syndrome
Gabriele-de Vries syndrome is characterized by mild-to-profound developmental delay / intellectual disability (DD/ID) in all affected individuals and a wide spectrum of functional and morphologic abnormalities. Intrauterine growth restriction or low birth weight and feeding difficulties are common. Congenital brain, eye, heart, kidney, genital, and/or skeletal system anomalies have also been reported. About half of affected individuals have neurologic manifestations, including hypotonia and gait abnormalities. Behavioral issues can include attention-deficit/hyperactivity disorder, anxiety, autism or autistic behavior, and schizoaffective disorder.
Intellectual disability, autosomal dominant 45
MedGen UID:
1616472
Concept ID:
C4539848
Mental or Behavioral Dysfunction
Developmental and epileptic encephalopathy, 56
MedGen UID:
1621755
Concept ID:
C4540034
Disease or Syndrome
Developmental and epileptic encephalopathy-56 (DEE56) is a neurodevelopmental disorder characterized by early-onset seizures in most patients, followed by impaired intellectual development, variable behavioral abnormalities, and sometimes additional neurologic features, such as ataxia (summary by Guella et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome
MedGen UID:
1620960
Concept ID:
C4540096
Disease or Syndrome
Mitochondrial myopathy and ataxia (MMYAT) is an autosomal recessive mtDNA depletion disorder characterized by cerebellar ataxia, congenital muscle involvement with histologic findings ranging from myopathic to dystrophic, and pigmentary retinopathy (summary by Donkervoort et al., 2019).
Intellectual disability, autosomal dominant 52
MedGen UID:
1615839
Concept ID:
C4540478
Mental or Behavioral Dysfunction
Coffin-Siris syndrome 6
MedGen UID:
1615540
Concept ID:
C4540499
Disease or Syndrome
Coffin-Siris syndrome (CSS) is classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degree, distinctive facial features, hypotonia, hirsutism/hypertrichosis, and sparse scalp hair. Congenital anomalies can include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Other findings commonly include feeding difficulties, slow growth, ophthalmologic abnormalities, and hearing impairment.
Intellectual disability, X-linked 107
MedGen UID:
1639885
Concept ID:
C4692652
Mental or Behavioral Dysfunction
PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome
MedGen UID:
1641154
Concept ID:
C4693860
Disease or Syndrome
Chung-Jansen syndrome (CHUJANS) is characterized by global developmental delay apparent from infancy, impaired intellectual development or learning difficulties, behavioral abnormalities, dysmorphic features, and obesity. The severity of the phenotype and additional features are variable (summary by Jansen et al., 2018).
Intellectual disability, autosomal dominant 57
MedGen UID:
1648280
Concept ID:
C4748003
Mental or Behavioral Dysfunction
MRD57 is an autosomal dominant neurodevelopmental disorder with a highly variable phenotype. Most affected individuals have delayed psychomotor development apparent in infancy or early childhood, language delay, and behavioral abnormalities. Additional features may include hypotonia, feeding problems, gastrointestinal issues, and dysmorphic facial features (summary by Reijnders et al., 2018).
Intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities
MedGen UID:
1648327
Concept ID:
C4748152
Disease or Syndrome
Any BAFopathy in which the cause of the disease is a mutation in the BCL11B gene.
Spinocerebellar ataxia 48
MedGen UID:
1648409
Concept ID:
C4748158
Disease or Syndrome
SCA48 is an autosomal dominant neurodegenerative disorder characterized by onset of gait ataxia and/or cognitive-affective symptoms in midadulthood. Patients may present with involvement of either system, but most eventually develop impairment in both. Features include gait ataxia, dysarthria, and dysphagia, as well as cognitive decline, deficits in executive function, and psychiatric or affective manifestations, such as depression, anxiety, and apathy. Additional more variable features may include movement abnormalities, such as parkinsonism, tremor, chorea, dystonia, and dysmetria; spasticity is not observed. Brain imaging shows selective atrophy of the posterior areas of the cerebellar vermis, often with bilateral T2-weighted hyperintensities in the dentate nuclei (the 'crab sign'), and diffusion tensor imaging (DTI) may show paucity of cerebellar connections to the brainstem and cerebrum. The presentation is consistent with a clinical diagnosis of cerebellar cognitive-affective syndrome (CCAS). The phenotype shows both inter- and intrafamilial variability as well as some clinical overlap with SCAR16, suggesting that mutations in the STUB1 gene result in a spectrum of neurodegenerative manifestations (summary by Genis et al., 2018; Cocozza et al., 2020; Palvadeau et al., 2020; Ravel et al., 2021). Magri et al. (2022) found evidence that heterozygous STUB1 variants alone do not cause disease but require a concurrent expanded repeat allele of the TBP gene (600075) for disease manifestation; see MOLECULAR GENETICS.
Macrocephaly, acquired, with impaired intellectual development
MedGen UID:
1648471
Concept ID:
C4748993
Disease or Syndrome
Neurodevelopmental disorder with central and peripheral motor dysfunction
MedGen UID:
1674767
Concept ID:
C5193049
Disease or Syndrome
Neurodevelopmental disorder with central and peripheral motor dysfunction (NEDCPMD) is an autosomal recessive neurologic disorder with a highly variable phenotype. At the severe end of the spectrum, patients may have hypotonia apparent from birth, necessitating mechanical respiration and tube-feeding, and global developmental delay with absence of reaction to touch and no eye contact. At the mild end of the spectrum, patients may present with infantile-onset progressive ataxia and demyelinating peripheral neuropathy. The disorder is caused by mutation in the NFASC gene, which has several neuronal- and glial-specific transcripts. The variable clinical phenotype may be caused by several factors, including the severity of the mutation, the selective involvement of distinct isoforms by pathogenic variants, and the presence of genetic modifiers (summary by Monfrini et al., 2019).
Developmental delay with variable intellectual impairment and behavioral abnormalities
MedGen UID:
1676192
Concept ID:
C5193092
Disease or Syndrome
Developmental delay with variable intellectual impairment and behavioral abnormalities (DDVIBA) is an autosomal dominant neurodevelopmental disorder. Most patients have impaired intellectual development with speech difficulties, and many have behavioral abnormalities, most commonly autism spectrum disorder (ASD), defects in attention, and/or hyperactivity. Many patients have dysmorphic features, although there is not a consistent gestalt. Additional more variable features may include hypotonia, somatic overgrowth with macrocephaly, mild distal skeletal anomalies, sleep disturbances, movement disorders, and gastrointestinal issues, such as constipation. The phenotype is highly variable (summary by Vetrini et al., 2019 and Torti et al., 2019).
O'Donnell-Luria-Rodan syndrome
MedGen UID:
1677602
Concept ID:
C5193138
Disease or Syndrome
O'Donnell-Luria-Rodan syndrome (ODLURO) is a neurodevelopmental disorder characterized by global developmental delay, speech delay, variably delayed intellectual development, and subtle dysmorphic features. Some patients may have autism, seizures, hypotonia, and/or feeding difficulties (summary by O'Donnell-Luria et al., 2019).
Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures
MedGen UID:
1684850
Concept ID:
C5231476
Disease or Syndrome
Patients with intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (IDDBCS) have impaired intellectual development or developmental delay of varying severity with impaired motor skills and language delay. Macrocephaly, obesity, and overgrowth are frequently seen. Approximately half of patients experience seizures, and neurobehavioral disorders including autism are usually present (Hamanaka et al., 2019; Kim et al., 2019).
Congenital heart defects, multiple types, 7
MedGen UID:
1714491
Concept ID:
C5394062
Congenital Abnormality
Multiple types of congenital heart defects-7 (CHTD7) is an autosomal dominant disorder with incomplete penetrance characterized mainly by tetralogy of Fallot but also including right-sided aortic arch, absent pulmonary valve, and other cardiac abnormalities (Jin et al., 2017, Reuter et al., 2019).
Beck-Fahrner syndrome
MedGen UID:
1711894
Concept ID:
C5394097
Disease or Syndrome
Beck-Fahrner syndrome (BEFAHRS) is a developmental disorder characterized by global developmental delay with variably impaired intellectual development. Affected individuals often have behavioral abnormalities, such as autistic features or attention deficit-hyperactivity disorder (ADHD), as well as learning disabilities. Most patients have hypotonia and dysmorphic facies. Some may have growth abnormalities, including overgrowth or poor growth, poor feeding, and rarely, seizures. Although both monoallelic and biallelic mutations have been reported, some heterozygous carriers in autosomal recessive families may have milder symptoms; thus, both groups are included in this entry (summary by Beck et al., 2020).
Nizon-Isidor syndrome
MedGen UID:
1715748
Concept ID:
C5394350
Disease or Syndrome
Nizon-Isidor syndrome (NIZIDS) is a neurodevelopmental disorder characterized by global developmental delay, mildly delayed walking, poor speech and language, variably impaired intellectual development, and behavioral abnormalities, such as autistic features or attention deficit-hyperactivity disorder (ADHD). Some patients may have additional features, including nonspecific facial dysmorphism, gastrointestinal difficulties, distal hand anomalies, and thin corpus callosum on brain imaging (summary by Nizon et al., 2019).
Leukoencephalopathy, motor delay, spasticity, and dysarthria syndrome
MedGen UID:
1719764
Concept ID:
C5394371
Disease or Syndrome
Leukoencephalopathy, motor delay, spasticity, and dysarthria syndrome (LEMSPAD) is characterized by a motor-predominant phenotype including motor developmental delay, speech articulation disorder, progressive spastic hemiplegia with hyperreflexia, and age-appropriate cognition (Mao et al., 2020).
Intellectual developmental disorder with autistic features and language delay, with or without seizures
MedGen UID:
1715081
Concept ID:
C5394447
Disease or Syndrome
Intellectual developmental disorder with autistic features and language delay, with or without seizures (IDDALDS), is a neurodevelopmental disorder characterized by global developmental delay, variable intellectual disability, impaired speech development, and behavioral abnormalities, most commonly on the autism spectrum. About half of patients develop seizures; brain imaging is typically normal. Additional features are highly variable, but may include chronic constipation, walking difficulties, and dysmorphic facial features (summary by Guo et al., 2019).
Agenesis of corpus callosum, cardiac, ocular, and genital syndrome
MedGen UID:
1718475
Concept ID:
C5394523
Disease or Syndrome
Agenesis of corpus callosum, cardiac, ocular, and genital syndrome (ACOGS) is a syndromic neurodevelopmental disorder characterized by global developmental delay and/or intellectual disability, corpus callosum agenesis or hypoplasia, craniofacial dysmorphisms, and ocular, cardiac, and genital anomalies (Accogli et al., 2019).
Cone-rod synaptic disorder syndrome, congenital nonprogressive
MedGen UID:
1773574
Concept ID:
C5436505
Disease or Syndrome
Congenital nonprogressive cone-rod synaptic disorder syndrome (CRSDS) is characterized by retinal and neurodevelopmental disease as well as occasional anomalies of glucose homeostasis. Patients exhibit low vision, photophobia, and nystagmus, and show an electronegative waveform in response to bright flash under dark adaptation on electroretinography, with severely reduced and delayed light-adapted responses. Neurodevelopmental features include poor to no language and autistic behaviors (Mechaussier et al., 2020).
Intellectual developmental disorder with seizures and language delay
MedGen UID:
1740295
Concept ID:
C5436574
Disease or Syndrome
SETD1B-related neurodevelopmental disorder (SETD1B-NDD) is characterized by developmental delay (mainly affecting speech and language), intellectual disability, seizures, autism spectrum disorder or autism-like behaviors, and additional behavioral concerns. Speech delay and/or language disorder has been reported in most affected individuals. Delay in gross motor skills and mild-to-moderate intellectual disability are common. Most affected individuals have seizures with variable onset and seizure type. Behavioral issues including hyperactivity, aggression, anxiety, and sleep disorders have been reported in approximately half of individuals. Less common features include ophthalmologic manifestations and feeding issues.
Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies
MedGen UID:
1759589
Concept ID:
C5436646
Disease or Syndrome
IDDEBF is a severe disorder characterized by impaired intellectual development, epilepsy, behavioral abnormalities, and coarse facies. Brain MRI findings may include delayed myelination in the deep parietal lobes (Kvarnung et al., 2018).
Neurodevelopmental disorder with speech impairment and dysmorphic facies
MedGen UID:
1758434
Concept ID:
C5436699
Disease or Syndrome
Neurodevelopmental disorder with speech impairment and dysmorphic facies (NEDSID) is characterized by developmental delay associated with mild to moderately impaired intellectual development or learning difficulties, behavioral or psychiatric abnormalities, and delayed speech and language acquisition. Additional features include dysmorphic facies, distal limb anomalies, gastrointestinal problems or feeding difficulties, and hypotonia. The phenotypic features and severity of the disorder are variable (summary by Kummeling et al., 2021).
Noonan syndrome 13
MedGen UID:
1761918
Concept ID:
C5436773
Disease or Syndrome
Noonan syndrome (NS) is characterized by characteristic facies, short stature, congenital heart defect, and developmental delay of variable degree. Other findings can include broad or webbed neck, unusual chest shape with superior pectus carinatum and inferior pectus excavatum, cryptorchidism, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities. Although birth length is usually normal, final adult height approaches the lower limit of normal. Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. Other structural defects include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Up to one fourth of affected individuals have mild intellectual disability, and language impairments in general are more common in NS than in the general population.
Epilepsy, progressive myoclonic, 12
MedGen UID:
1778162
Concept ID:
C5543069
Disease or Syndrome
Progressive myoclonic epilepsy-12 (EPM12) is an autosomal recessive neurologic disorder characterized by onset of tonic-clonic seizures and/or myoclonus in the second decade of life. Affected individuals develop cerebellar ataxia associated with progressive cerebral and cerebellar atrophy on brain imaging. Most patients lose ambulation and become wheelchair-bound. Additional more variable features include mild cognitive dysfunction or psychiatric manifestations, such as depression or anxiety (summary by Mazzola et al., 2021). For a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800).
Neurodevelopmental disorder with dysmorphic facies and variable seizures
MedGen UID:
1784197
Concept ID:
C5543268
Disease or Syndrome
Neurodevelopmental disorder with dysmorphic facies and variable seizures (NEDDFAS) is an autosomal recessive disorder characterized by global developmental delay apparent in early childhood. Patients have mildly impaired intellectual development, often with speech delay or behavioral abnormalities. Some may have seizures. Most have nonspecific dysmorphic facial features. Additional findings may include brain imaging abnormalities, mild skeletal defects, and renal abnormalities, although the renal anomalies may be unrelated (summary by Shao et al., 2021).
Parkinsonism with polyneuropathy
MedGen UID:
1783451
Concept ID:
C5543299
Disease or Syndrome
Parkinsonism with polyneuropathy (PKNPY) is an autosomal dominant disorder characterized by asymmetrical tremor-dependent parkinsonism. The age of onset ranges from the late forties to mid-sixties, and patients have a good response to levodopa (summary by Lin et al., 2020).
Mitochondrial dna depletion syndrome 16B (neuroophthalmic type)
MedGen UID:
1780329
Concept ID:
C5543632
Disease or Syndrome
Mitochondrial DNA depletion syndrome-16B (MTDPS16B) is an autosomal recessive childhood-onset and progressive neuroophthalmic mtDNA depletion disorder characterized by optic atrophy, mixed polyneuropathy, spinal and cerebellar ataxia, and generalized chorea (Dosekova et al., 2020).
White-Kernohan syndrome
MedGen UID:
1785087
Concept ID:
C5543635
Disease or Syndrome
White-Kernohan syndrome (WHIKERS) is a neurodevelopmental disorder characterized by global developmental delay with variably impaired intellectual development, hypotonia, and characteristic facial features. Some patients may have abnormalities of other systems, including genitourinary and skeletal (summary by White et al., 2021).
Dyskinesia with orofacial involvement, autosomal dominant
MedGen UID:
1790407
Concept ID:
C5551343
Disease or Syndrome
ADCY5 dyskinesia is a hyperkinetic movement disorder (more prominent in the face and arms than the legs) characterized by infantile to late-adolescent onset of chorea, athetosis, dystonia, myoclonus, or a combination of these. To date, affected individuals have had overlapping (but not identical) manifestations with wide-ranging severity. The facial movements are typically periorbital and perioral. The dyskinesia is prone to episodic or paroxysmal exacerbation lasting minutes to hours, and may occur during sleep. Precipitating factors in some persons have included emotional stress, intercurrent illness, sneezing, or caffeine; in others, no precipitating factors have been identified. In some children, severe infantile axial hypotonia results in gross motor delays accompanied by chorea, sometimes with language delays. The overall tendency is for the abnormal movements to stabilize in early middle age, at which point they may improve in some individuals; less commonly, the abnormal movements are slowly progressive, increasing in severity and frequency.
Neuroocular syndrome
MedGen UID:
1790414
Concept ID:
C5551362
Disease or Syndrome
Neuroocular syndrome (NOC) encompasses a broad spectrum of overlapping anomalies, with developmental delay or impaired intellectual development as a consistent finding. Eye abnormalities show marked variability in the type and severity of defects, and include anophthalmia, microphthalmia, and coloboma. Other common systemic features include congenital heart and kidney defects, hypotonia, failure to thrive, and microcephaly (summary by Chowdhury et al., 2021).
Usmani-Riazuddin syndrome, autosomal dominant
MedGen UID:
1794162
Concept ID:
C5561952
Disease or Syndrome
Autosomal dominant Usmani-Riazzudin syndrome (USRISD) is a neurodevelopmental disorder characterized by global developmental delay with impaired intellectual development and speech delay, hypotonia, and behavioral abnormalities, most commonly aggressive behavior. More variable additional features may include seizures and distal limb anomalies (summary by Usmani et al., 2021).
Developmental delay, impaired speech, and behavioral abnormalities
MedGen UID:
1794167
Concept ID:
C5561957
Disease or Syndrome
Developmental delay, impaired speech, and behavioral abnormalities (DDISBA) is characterized by global developmental delay apparent from early childhood. Intellectual disability can range from mild to severe. Additional variable features may include dysmorphic facial features, seizures, hypotonia, motor abnormalities such as Tourette syndrome or dystonia, and hearing loss (summary by Cousin et al., 2021).
Neurodevelopmental disorder with hypotonia and brain abnormalities
MedGen UID:
1794187
Concept ID:
C5561977
Disease or Syndrome
Neurodevelopmental disorder with hypotonia and brain abnormalities (NEDHYBA) is characterized by impaired development of motor skills, cognitive function, and speech acquisition beginning in infancy or early childhood. Some affected individuals may have feeding difficulties, seizures, behavioral abnormalities, and nonspecific dysmorphic facial features. Brain imaging shows variable abnormalities, including corpus callosum defects, cerebellar defects, and decreased white matter volume. There is significant phenotypic variability (summary by Duncan et al., 2021).
Neurodevelopmental disorder with impaired language and ataxia and with or without seizures
MedGen UID:
1794216
Concept ID:
C5562006
Disease or Syndrome
Neurodevelopmental disorder with impaired language and ataxia and with or without seizures (NEDLAS) is characterized by axial hypotonia and global developmental delay apparent in early infancy. Affected individuals have delayed walking with gait ataxia and poor language development. Behavioral abnormalities also commonly occur. The severity is highly variable: a subset of patients have a more severe phenotype with early-onset seizures resembling epileptic encephalopathy, inability to walk or speak, and hypomyelination on brain imaging (summary by Stolz et al., 2021).
Neurodevelopmental disorder with hyperkinetic movements and dyskinesia
MedGen UID:
1794248
Concept ID:
C5562038
Disease or Syndrome
Neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD) is an autosomal recessive complex neurologic disorder characterized by severe global developmental delay with axial hypotonia, impaired intellectual development, poor overall growth, and abnormal involuntary hyperkinetic movements, including dystonia, myoclonus, spasticity, and orofacial dyskinesia. It is the most severe manifestation of ADCY5-related dyskinetic disorders (summary by Okamoto et al., 2021 and Kaiyrzhanov et al., 2021).
Rauch-Steindl syndrome
MedGen UID:
1794271
Concept ID:
C5562061
Disease or Syndrome
Rauch-Steindl syndrome (RAUST) is characterized by poor pre- and postnatal growth, sometimes with short stature and small head circumference, characteristic dysmorphic facial features, and variable developmental delay with delayed motor and speech acquisition and impaired intellectual function that can be mild. Other features may include hypotonia and behavioral abnormalities. The phenotype represents a mild form of Wolf-Hirschhorn syndrome (WHS; 194190), which is a contiguous gene deletion syndrome caused by heterozygous deletion of several genes on chromosome 4p16. The clinical features of RAUST are similar to but milder than those of WHS, with less severe dysmorphic facial features, less severe developmental disabilities in general, and absence of a seizure disorder. The phenotype and expressivity of RAUST is highly variable (summary by Rauch et al., 2001; Zanoni et al., 2021).
Systemic lupus erythematosus 17
MedGen UID:
1804329
Concept ID:
C5676884
Disease or Syndrome
Systemic lupus erythematosus-17 (SLE17) is an X-linked dominant autoimmune disorder characterized by onset of systemic autoinflammatory symptoms in the first decades of life. Only affected females have been reported. Features may include classic features of SLE, such as malar rash and arthralgias, or can include less common entities such as hemiplegia and neuromyelitis optica (NMO). Laboratory studies show the presence of autoantibodies and enhanced NFKB (164011) signaling, the latter being consistent with a gain-of-function effect (Brown et al., 2022). For a phenotypic description and a discussion of genetic heterogeneity of systemic lupus erythematosus (SLE), see 152700.
Hypogonadotropic hypogonadism 26 with or without anosmia
MedGen UID:
1811919
Concept ID:
C5676903
Disease or Syndrome
HH26 is characterized by micropenis and cryptorchidism at birth in male patients, and absent puberty and anosmia in male or female patients. Some affected individuals also exhibit craniosynostosis (Davis et al., 2020). Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. Idiopathic hypogonadotropic hypogonadism can be caused by an isolated defect in gonadotropin-releasing hormone (GNRH; 152760) release, action, or both. Other associated nonreproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss, occur with variable frequency. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism has been called 'Kallmann syndrome (KS),' whereas in the presence of a normal sense of smell, it has been termed 'normosmic idiopathic hypogonadotropic hypogonadism (nIHH)' (summary by Raivio et al., 2007). Because families have been found to segregate both KS and nIHH, the disorder is here referred to as 'hypogonadotropic hypogonadism with or without anosmia (HH).' For a discussion of genetic heterogeneity of hypogonadotropic hypogonadism with or without anosmia as well as a discussion of oligogenicity of this disorder, see 147950.
Intellectual disability and myopathy syndrome
MedGen UID:
1808193
Concept ID:
C5676904
Disease or Syndrome
Intellectual disability and myopathy syndrome (IDMYS) is an autosomal recessive developmental disorder characterized by global developmental delay with mildly impaired intellectual development, hypotonia, muscle weakness and fatigue, and white matter abnormalities on brain imaging. Variable additional features may include sensorineural hearing loss, dysmorphic facies, and progressive heart disease (summary by Smeland et al., 2019).
Neurodevelopmental disorder with or without variable movement or behavioral abnormalities
MedGen UID:
1802087
Concept ID:
C5676908
Disease or Syndrome
Neurodevelopmental disorder with or without variable movement or behavioral abnormalities (NEDMAB) is an autosomal dominant disorder characterized by mildly to severely impaired intellectual development and, in some patients, movement abnormalities consisting of tremors, cerebellar ataxia, or extrapyramidal symptoms. Movement abnormalities have onset in childhood or adolescence. Other variable features include autism spectrum disorder or autistic features and epilepsy.
Parkinsonism-dystonia 3, childhood-onset
MedGen UID:
1808365
Concept ID:
C5676913
Disease or Syndrome
Childhood-onset parkinsonism-dystonia-3 (PKDYS3) is an autosomal recessive neurodegenerative disorder with onset in infancy or early childhood. Affected individuals present with progressive movement abnormalities, including parkinsonism with tremor, dystonia, myoclonus ataxia, and hyperkinetic movements such as ballismus. The parkinsonism features may be responsive to treatment with levodopa, although many patients develop levodopa-induced dyskinesia. Some patients may have mild cognitive impairment or psychiatric disturbances (summary by Burke et al., 2018 and Skorvanek et al., 2022). For a discussion of genetic heterogeneity of PKDYS, see 613135.
Neurodevelopmental disorder with dystonia and seizures
MedGen UID:
1804461
Concept ID:
C5677004
Disease or Syndrome
Neurodevelopmental disorder with dystonia and seizures (NEDDS) is a severe autosomal recessive disorder characterized by hypotonia and dystonic posturing apparent from early infancy. Affected individuals show global developmental delay with inability to walk or speak and have profoundly impaired intellectual development, often with behavioral abnormalities. Additional features may include other extrapyramidal movements, seizures or seizure-like activity, and cerebellar hypoplasia on brain imaging (Sleiman et al., 2022).
Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1
MedGen UID:
1808104
Concept ID:
C5677021
Disease or Syndrome
Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome-1 (CFSMR1) is characterized by cranial involvement with macrocrania at birth, brachycephaly, anomalies of middle fossa structures including hypoplasia of corpus callosum, enlargement of septum pellucidum, and dilated lateral ventricles, as well as cortical atrophy and hypodensity of the gray matter. Facial dysmorphisms include flat face, hypertelorism, epicanthal folds, synophrys, broad nasal bridge, cleft lip and cleft palate, and low-set posteriorly rotated ears. Patients also exhibit short neck and multiple costal and vertebral anomalies. The face is rather characteristic, and various authors have consistently reported affable/friendly personality, despite intellectual delay (summary by Alanay et al., 2014). Genetic Heterogeneity of Craniofacial Dysmorphism, Skeletal Anomalies, and Impaired Intellectual Development Syndrome CFSMR2 (616994) is caused by mutation in the RAB5IF gene (619960) on chromosome 20q11.
Chilton-Okur-Chung neurodevelopmental syndrome
MedGen UID:
1803276
Concept ID:
C5677022
Disease or Syndrome
Chilton-Okur-Chung neurodevelopmental syndrome (CHOCNS) is characterized mainly by global developmental delay with variably impaired intellectual development and occasional speech delay. Most patients have behavioral abnormalities, including autism spectrum disorder, ADHD, and aggression. About half of patients have dysmorphic facial features, and about half have nonspecific brain abnormalities, including thin corpus callosum. Rare involvement of other organ systems may be present. At least 1 child with normal development at age 2.5 years has been reported (Chilton et al., 2020).
Chromosome Xq13 duplication syndrome
MedGen UID:
1809227
Concept ID:
C5677057
Disease or Syndrome
DeSanto-Shinawi syndrome due to WAC point mutation
MedGen UID:
1841517
Concept ID:
C5681129
Disease or Syndrome
WAC-related intellectual disability (ID) is typically characterized by variable degrees of developmental delay and/or intellectual disability. Behavioral abnormalities including anxiety, attention-deficit/hyperactivity disorder, and/or autism spectrum disorder are observed in the majority of older children and adults. Most affected infants have significant but nonspecific features at birth such as neonatal hypotonia and feeding problems. Some affected individuals come to medical attention with respiratory or vision problems. Facial features may be mildly dysmorphic, but are nonspecific. To date, 18 individuals have been identified with WAC-related ID.
Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects
MedGen UID:
1823972
Concept ID:
C5774199
Disease or Syndrome
Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects (IDDMDS) is an autosomal recessive disorder characterized by global developmental delay apparent in infancy manifest as speech delay and late walking by a few years. Affected individuals have hypertonia or, more rarely, hypotonia; a notable common feature is facial myokymia with corresponding EMG findings. Additional features include distal skeletal defects such as joint contractures, hypo- or areflexia, and hernia (Marafi et al., 2022).
Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly
MedGen UID:
1824005
Concept ID:
C5774232
Disease or Syndrome
Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-Pelger-Huet anomaly (NEDFLPH) is an autosomal recessive disorder characterized by global developmental delay with severely impaired intellectual development. Affected individuals often have behavioral abnormalities and may have variable findings on brain imaging, such as thin corpus callosum. Laboratory studies show nuclear lobulation defects in a subset of neutrophils, indicating a pseudo-Pelger-Huet anomaly (see 169400) and suggesting defects in the integrity of the nuclear envelope, where TMEM147 localizes (Thomas et al., 2022).
Neurodevelopmental disorder with eye movement abnormalities and ataxia
MedGen UID:
1824014
Concept ID:
C5774241
Disease or Syndrome
Neurodevelopmental disorder with eye movement abnormalities and ataxia (NEDEMA) is characterized by global developmental delay apparent from infancy. Affected individuals show delayed walking with an unsteady gait, variably impaired intellectual development, learning disabilities, and speech difficulties. Abnormal eye movements, which are often noted in early childhood, include opsoclonus, nystagmus, and strabismus. Some patients have seizures, which may be refractory (Lu et al., 2022).
Atelis syndrome 2
MedGen UID:
1824055
Concept ID:
C5774282
Disease or Syndrome
Atelis syndrome-2 (ATELS2) is an autosomal recessive disorder characterized by poor overall growth with microcephaly and short stature, dysmorphic facial features, and congenital cardiac defects. Additional more variable features may include hematologic abnormalities, variable ocular abnormalities, motor delay, and anxiety. Patient cells exhibit a unique chromosomal instability phenotype consisting of segmented and dicentric chromosomes with mosaic variegated hyperploidy (Grange et al., 2022). See also ATELS1 (620184), caused by mutation in the SLF2 gene (610348). For a discussion of genetic heterogeneity of MVA, see MVA1 (257300).
Intellectual developmental disorder, X-linked 111
MedGen UID:
1840204
Concept ID:
C5829568
Mental or Behavioral Dysfunction
X-linked intellectual developmental disorder-111 (XLID111) is a neurodevelopmental disorder characterized by different degrees of impaired intellectual development associated with motor, speech, and behavioral impairments (El Chehadeh et al., 2022).
Neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum
MedGen UID:
1840932
Concept ID:
C5830296
Disease or Syndrome
Neurodevelopmental disorder with seizures, spasticity, and partial or complete agenesis of the corpus callosum (NEDSSCC) is an autosomal recessive disorder characterized by axial hypotonia and global developmental delay apparent from the first days or months of life. Affected individuals often have feeding difficulties and develop early-onset seizures that tend to be well-controlled. Other features include peripheral spasticity with hyperreflexia, variable dysmorphic features, impaired intellectual development, behavioral abnormalities, and hypoplasia or absence of the corpus callosum on brain imaging (Faqeih et al., 2023).
Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures
MedGen UID:
1841001
Concept ID:
C5830365
Disease or Syndrome
Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures (NEDLBAS), is characterized by global developmental delay with variably impaired intellectual development apparent from infancy or early childhood. Affected individuals have significant speech delay, and most demonstrate behavioral abnormalities, including autistic features. About half of patients develop seizures, which may be controlled or refractory. More variable features include hypotonia, feeding difficulties, and subtle facial dysmorphism (Schalk et al., 2022).
Intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities
MedGen UID:
1841073
Concept ID:
C5830437
Mental or Behavioral Dysfunction
Autosomal dominant intellectual developmental disorder-71 with behavioral abnormalities (MRD71) is a neurodevelopmental disorder characterized by global developmental delay with hypotonia, speech delay, and variably impaired cognitive development. Almost all affected individuals show marked behavioral manifestations, including autism spectrum disorder (ASD), ADHD, hypersensitivity, and aggression. Many have dysmorphic features, although there is not a common gestalt (Harris et al., 2021).
Intellectual developmental disorder, autosomal dominant 72
MedGen UID:
1841248
Concept ID:
C5830612
Mental or Behavioral Dysfunction
Autosomal dominant intellectual developmental disorder-72 (MRD72) is characterized by developmental delay, predominant speech delay, autistic or attention-deficit/hyperactivity disorder features, overfriendliness, generalized hypotonia, overweight/obesity, and dysmorphic features (Cuinat et al., 2022).
Teebi hypertelorism syndrome 1
MedGen UID:
989457
Concept ID:
CN306405
Disease or Syndrome
Teebi hypertelorism syndrome-1 (TBHS1) is an autosomal dominant disorder characterized by hypertelorism with upslanting palpebral fissures, prominent forehead, broad and depressed nasal bridge with short nose, thick eyebrows, and widow's peak. Additional features include small broad hands with mild interdigital webbing and shawl scrotum. Umbilical malformations, cardiac defects, natal teeth, cleft lip/palate, congenital diaphragmatic hernia, and malformations of the central nervous system (ventriculomegaly, abnormal corpus callosum) have also been reported. Development is typically normal, although some patients with developmental delays have been reported (summary by Bhoj et al., 2015). Genetic Heterogeneity of Teebi Hypertelorism Syndrome Teebi hypertelorism syndrome-2 (TBHS2; 619736) is caused by mutation in the CDH11 gene (600023) on chromosome 16q21.

Professional guidelines

PubMed

Walter HJ, Bukstein OG, Abright AR, Keable H, Ramtekkar U, Ripperger-Suhler J, Rockhill C
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Michaelides A, Zis P
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Recent clinical studies

Etiology

Penninx BW, Pine DS, Holmes EA, Reif A
Lancet 2021 Mar 6;397(10277):914-927. Epub 2021 Feb 11 doi: 10.1016/S0140-6736(21)00359-7. PMID: 33581801Free PMC Article
Zemła AJ, Nowicka-Sauer K, Jarmoszewicz K, Wera K, Batkiewicz S, Pietrzykowska M
Anaesthesiol Intensive Ther 2019;51(1):64-69. doi: 10.5603/AIT.2019.0013. PMID: 31280554
Dean E
Nurs Stand 2016 Jul 13;30(46):15. doi: 10.7748/ns.30.46.15.s17. PMID: 27406490
Kupfer DJ
Dialogues Clin Neurosci 2015 Sep;17(3):245-6. doi: 10.31887/DCNS.2015.17.3/dkupfer. PMID: 26487805Free PMC Article
Stonerock GL, Hoffman BM, Smith PJ, Blumenthal JA
Ann Behav Med 2015 Aug;49(4):542-56. doi: 10.1007/s12160-014-9685-9. PMID: 25697132Free PMC Article

Diagnosis

Med Lett Drugs Ther 2023 Aug 7;65(1682):121-128. doi: 10.58347/tml.2023.1682a. PMID: 37516898
Vu V, Conant-Norville D
Psychiatr Clin North Am 2021 Sep;44(3):373-380. Epub 2021 Jun 16 doi: 10.1016/j.psc.2021.04.005. PMID: 34372994
Knowles KA, Olatunji BO
Clin Psychol Rev 2020 Dec;82:101928. Epub 2020 Oct 10 doi: 10.1016/j.cpr.2020.101928. PMID: 33091745Free PMC Article
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Anaesthesiol Intensive Ther 2019;51(1):64-69. doi: 10.5603/AIT.2019.0013. PMID: 31280554
Kupfer DJ
Dialogues Clin Neurosci 2015 Sep;17(3):245-6. doi: 10.31887/DCNS.2015.17.3/dkupfer. PMID: 26487805Free PMC Article

Therapy

Hatoum T, Raj S, Sheldon RS
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Prognosis

Wang YH, Li JQ, Shi JF, Que JY, Liu JJ, Lappin JM, Leung J, Ravindran AV, Chen WQ, Qiao YL, Shi J, Lu L, Bao YP
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Clinical prediction guides

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Recent systematic reviews

Aloufi MA, Jarden RJ, Gerdtz MF, Kapp S
Nurse Educ Today 2021 Jul;102:104877. Epub 2021 Mar 18 doi: 10.1016/j.nedt.2021.104877. PMID: 33905898
Simpson CA, Diaz-Arteche C, Eliby D, Schwartz OS, Simmons JG, Cowan CSM
Clin Psychol Rev 2021 Feb;83:101943. Epub 2020 Oct 29 doi: 10.1016/j.cpr.2020.101943. PMID: 33271426
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Boyle NB, Lawton C, Dye L
Nutrients 2017 Apr 26;9(5) doi: 10.3390/nu9050429. PMID: 28445426Free PMC Article
Stonerock GL, Hoffman BM, Smith PJ, Blumenthal JA
Ann Behav Med 2015 Aug;49(4):542-56. doi: 10.1007/s12160-014-9685-9. PMID: 25697132Free PMC Article

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