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Chronic constipation

MedGen UID:
98325
Concept ID:
C0401149
Sign or Symptom
Synonym: Constipation, chronic
SNOMED CT: Chronic constipation (236069009)
 
HPO: HP:0012450

Definition

Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • Chronic constipation

Conditions with this feature

Mucopolysaccharidosis type 6
MedGen UID:
44514
Concept ID:
C0026709
Disease or Syndrome
Mucopolysaccharidosis type VI (MPS6) is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B. Clinical features and severity are variable, but usually include short stature, hepatosplenomegaly, dysostosis multiplex, stiff joints, corneal clouding, cardiac abnormalities, and facial dysmorphism. Intelligence is usually normal (Azevedo et al., 2004).
Familial Mediterranean fever
MedGen UID:
45811
Concept ID:
C0031069
Disease or Syndrome
Familial Mediterranean fever (FMF) is divided into two phenotypes: type 1 and type 2. FMF type 1 is characterized by recurrent short episodes of inflammation and serositis including fever, peritonitis, synovitis, pleuritis, and, rarely, pericarditis and meningitis. The symptoms and severity vary among affected individuals, sometimes even among members of the same family. Amyloidosis, which can lead to renal failure, is the most severe complication, if untreated. FMF type 2 is characterized by amyloidosis as the first clinical manifestation of FMF in an otherwise asymptomatic individual.
Prader-Willi syndrome
MedGen UID:
46057
Concept ID:
C0032897
Disease or Syndrome
Prader-Willi syndrome (PWS) is characterized by severe hypotonia and feeding difficulties in early infancy, followed in later infancy or early childhood by excessive eating and gradual development of morbid obesity (unless eating is externally controlled). Motor milestones and language development are delayed. All individuals have some degree of cognitive impairment. A distinctive behavioral phenotype (with temper tantrums, stubbornness, manipulative behavior, and obsessive-compulsive characteristics) is common. Hypogonadism is present in both males and females and manifests as genital hypoplasia, incomplete pubertal development, and, in most, infertility. Short stature is common (if not treated with growth hormone); characteristic facial features, strabismus, and scoliosis are often present.
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.
Abortive cerebellar ataxia
MedGen UID:
66358
Concept ID:
C0221061
Disease or Syndrome
'Behr syndrome' is a clinical term that refers to the constellation of early-onset optic atrophy accompanied by neurologic features, including ataxia, pyramidal signs, spasticity, and mental retardation (Behr, 1909; Thomas et al., 1984). Patients with mutations in genes other than OPA1 can present with clinical features reminiscent of Behr syndrome. Mutations in one of these genes, OPA3 (606580), result in type III 3-methylglutaconic aciduria (MGCA3; 258501). Lerman-Sagie (1995) noted that the abnormal urinary pattern in MGCA3 may not be picked up by routine organic acid analysis, suggesting that early reports of Behr syndrome with normal metabolic features may actually have been 3-methylglutaconic aciduria type III.
Deficiency of malonyl-CoA decarboxylase
MedGen UID:
91001
Concept ID:
C0342793
Disease or Syndrome
Malonyl-CoA decarboxylase deficiency is an uncommon inherited metabolic disease. The characteristic phenotype is variable, but may include developmental delay in early childhood, seizures, hypotonia, diarrhea, vomiting, metabolic acidosis, hypoglycemia, ketosis, abnormal urinary compounds, lactic acidemia, and hypertrophic cardiomyopathy (Sweetman and Williams, 2001).
Troyer syndrome
MedGen UID:
97950
Concept ID:
C0393559
Disease or Syndrome
Troyer syndrome is characterized by progressive spastic paraparesis, dysarthria, pseudobulbar palsy, distal amyotrophy, short stature, and subtle skeletal abnormalities. Most affected children exhibit delays in walking and speech and difficulty in managing oral secretions, followed by increased lower-limb spasticity and slow deterioration in both gait and speech. Mild cerebellar signs are common. The most severely affected individuals have choreoathetosis. Emotional lability / difficulty in controlling emotions and affective disorders, such as inappropriate euphoria and/or crying, are frequently described. Life expectancy is normal.
Curry-Jones syndrome
MedGen UID:
167083
Concept ID:
C0795915
Disease or Syndrome
Curry-Jones syndrome (CRJS) is a multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas (summary by Twigg et al., 2016).
TNF receptor-associated periodic fever syndrome (TRAPS)
MedGen UID:
226899
Concept ID:
C1275126
Disease or Syndrome
Familial periodic fever (FPF) is an autoinflammatory disorder characterized by recurrent fever with localized myalgia and painful erythema. Febrile attacks may last 1 or 2 days but often last longer than 1 week. Arthralgia of large joints, abdominal pain, conjunctivitis, and periorbital edema are common features. During attacks, painless cutaneous lesions may develop on the trunk or extremities and may migrate distally (review by Drenth and van der Meer, 2001).
Currarino triad
MedGen UID:
323460
Concept ID:
C1531773
Disease or Syndrome
The Currarino syndrome is an autosomal dominant form of hereditary sacral dysgenesis that classically consists of the triad of sacral malformation, presacral mass, and anorectal malformations. However, other features include neonatal-onset bowel obstruction, chronic constipation, recurrent perianal sepsis, renal/urinary tract anomalies, female internal genital anomalies, tethered spinal cord, and anterior meningocele. There is marked inter- and intrafamilial variability, and up to 33% of patients are asymptomatic (summary by Wang et al., 2006).
FG syndrome 5
MedGen UID:
336854
Concept ID:
C1845119
Disease or Syndrome
Additional features seen in some people with FG syndrome include widely set eyes (hypertelorism), an upswept frontal hairline, and a large head compared to body size (relative macrocephaly). Other health problems have also been reported, including heart defects, seizures, undescended testes (cryptorchidism) in males, and a soft out-pouching in the lower abdomen (an inguinal hernia).\n\nThe physical features of FG syndrome include weak muscle tone (hypotonia), broad thumbs, and wide first (big) toes. Abnormalities of the tissue connecting the left and right halves of the brain (the corpus callosum) are also common. Most affected individuals have constipation, and many have abnormalities of the anus such as an obstruction of the anal opening (imperforate anus). People with FG syndrome also tend to have a distinctive facial appearance including small, underdeveloped ears; a tall, prominent forehead; and outside corners of the eyes that point downward (down-slanting palpebral fissures).\n\nFG syndrome affects intelligence and behavior. Almost everyone with the condition has intellectual disability, which ranges from mild to severe. Affected individuals tend to be friendly, inquisitive, and hyperactive, with a short attention span. Compared to people with other forms of intellectual disability, their socialization and daily living skills are strong, while verbal communication and language skills tend to be weaker.\n\nFG syndrome is a genetic condition that affects many parts of the body and occurs almost exclusively in males. "FG" represents the surname initials of the first family diagnosed with the disorder.
Corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome
MedGen UID:
335185
Concept ID:
C1845446
Disease or Syndrome
Corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome is a developmental anomalies syndrome characterized by coloboma of the iris and optic nerve, facial dysmorphism (high forehead, microretrognathia, low-set ears), intellectual deficit, agenesis of the corpus callosum (ACC), sensorineural hearing loss, skeletal anomalies and short stature.
FG syndrome 3
MedGen UID:
375687
Concept ID:
C1845567
Disease or Syndrome
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.
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.
Syndromic X-linked intellectual disability 14
MedGen UID:
372646
Concept ID:
C1970822
Disease or Syndrome
Any X-linked syndromic intellectual disability in which the cause of the disease is a mutation in the UPF3B gene.
Chromosome 6pter-p24 deletion syndrome
MedGen UID:
393396
Concept ID:
C2675486
Disease or Syndrome
Distal monosomy 6p is responsible for a distinct chromosome deletion syndrome with a recognizable clinical picture including intellectual deficit, ocular abnormalities, hearing loss, and facial dysmorphism.
Vesicoureteral reflux 3
MedGen UID:
462277
Concept ID:
C3150927
Disease or Syndrome
Any vesicoureteral reflux in which the cause of the disease is a mutation in the SOX17 gene.
Congenital disorder of glycosylation type Ir
MedGen UID:
482714
Concept ID:
C3281084
Disease or Syndrome
Congenital disorder of glycosylation type Ir (CDG1R) is an autosomal recessive disorder characterized by developmental delay, failure to thrive, feeding difficulties, hypotonia, and strabismus. Transferrin analysis demonstrates underglycosylation (summary by Pi et al., 2022). For a discussion of the classification of CDGs, see CDG1A (212065).
Cerebellar dysfunction with variable cognitive and behavioral abnormalities
MedGen UID:
766575
Concept ID:
C3553661
Disease or Syndrome
Cerebellar dysfunction with variable cognitive and behavioral abnormalities (CECBA) is an autosomal dominant neurologic disorder with significant phenotypic heterogeneity, even within families. The disorder is most often diagnosed through genetic analysis with retrospective clinical phenotyping. Symptom onset is usually in early childhood, although later onset, even in adulthood, has been reported. Most affected individuals show global developmental delay from early childhood, particularly of motor and language skills. Many have mild intellectual disability; behavioral and psychiatric abnormalities such as autism and obsessive-compulsive disorder are also often observed. The movement disorder is prominent and may include cerebellar signs such as ataxia, tremor, dysmetria, poor coordination, and dysarthria. Other abnormal movements including spasticity, myoclonus, and dystonia have been reported, thus widening the phenotypic spectrum. Brain imaging is usually normal, but may show cerebellar atrophy or nonspecific white matter lesions. Variable dysmorphic facial features may also be present (summary by Thevenon et al., 2012; Jacobs et al., 2021; Wijnen et al., 2020).
Intellectual disability, X-linked 99
MedGen UID:
813076
Concept ID:
C3806746
Mental or Behavioral Dysfunction
Any non-syndromic X-linked intellectual disability in which the cause of the disease is a mutation in the USP9X gene.
Al-Raqad syndrome
MedGen UID:
897610
Concept ID:
C4085595
Disease or Syndrome
PMP22-RAI1 contiguous gene duplication syndrome
MedGen UID:
894862
Concept ID:
C4225255
Disease or Syndrome
Yuan-Harel-Lupski syndrome is a complex neurodevelopmental disorder characterized by global developmental delay and early-onset peripheral neuropathy. The disorder comprises features of both demyelinating Charcot-Marie-Tooth disease type 1A (CMT1A; 118220), which results from duplication of the PMP22 gene on 17p12, and Potocki-Lupski syndrome (PTLS; 610883), which results from duplication of a slightly proximal region on 17p11.2 that includes the RAI1 gene. These 2 loci are about 2.5 Mb apart. The resultant YUHAL phenotype may be more severe in comparison to the individual contributions of each gene, with particularly early onset of peripheral neuropathy and features of both central and peripheral nervous system involvement (summary by Yuan et al., 2015).
Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome
MedGen UID:
895574
Concept ID:
C4225276
Disease or Syndrome
Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities (NEDHSB) is an autosomal recessive disorder characterized by severe neurologic impairment including impaired intellectual development, epilepsy, microcephaly, abnormal muscle tone, and sensorineural hearing loss. Most affected individuals are nonambulatory, cannot sit unassisted, and have no speech development. More variable features include feeding difficulties, poor growth, cortical visual impairment, spasticity, scoliosis, immunodeficiency, and thrombocytopenia (Tanaka et al., 2015).
Houge-Janssens syndrome 2
MedGen UID:
899880
Concept ID:
C4225352
Disease or Syndrome
PPP2R1A-related neurodevelopmental disorder (NDD) is characterized by: severe, persistent hypotonia; developmental delay with variable intellectual outcomes, typically in the moderate-to-severe intellectual disability range; seizures (more commonly seen in individuals with microcephaly and/or severe intellectual disability); attention-deficit/hyperactivity disorder and other behavioral problems (anxiousness, repetitive movements, self-injurious or destructive behavior, and autism spectrum disorder); feeding and swallowing issues; and dysmorphic features of the head and face. A minority of affected individuals have ear anomalies, hearing loss, ptosis, generalized joint hypermobility, and patent ductus arteriosus. Brain MRI findings are nonspecific but typically include complete or partial agenesis of the corpus callosum. Nonprogressive ventriculomegaly may be seen in a subset of affected individuals and is often associated with specific pathogenic variants in PPP2R1A: c.544C>T (p.Arg182Trp) and c.547C>T (p.Arg183Trp).
Developmental and epileptic encephalopathy, 47
MedGen UID:
934652
Concept ID:
C4310685
Disease or Syndrome
Developmental and epileptic encephalopathy-47 (DEE47) is a neurologic disorder characterized by onset of intractable seizures in the first days or weeks of life. EEG shows background slowing and multifocal epileptic spikes, and may show hypsarrhythmia. Most patients have developmental regression after seizure onset and show persistent intellectual disability and neurologic impairment, although the severity is variable. Treatment with phenytoin, a voltage-gated sodium channel blocker, may be beneficial (summary by Guella et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
MedGen UID:
934707
Concept ID:
C4310740
Disease or Syndrome
TRIO-related intellectual disability (ID) is characterized by delay in acquisition of motor and language skills, mild to borderline intellectual disability, and neurobehavioral problems (including autistic traits or autism spectrum disorder, attention-deficit/hyperactivity disorder, and/or aggression). Neonatal or infantile feeding difficulties including poor suck, impaired bottle feeding, and failure to thrive are common and are often the presenting finding. Other findings can include microcephaly, variable hand and dental abnormalities, and suggestive facial features. Only ten of the 20 individuals with a TRIO pathogenic variant reported to date had sufficient information to make preliminary generalizations about clinical manifestations; it is anticipated that the phenotype of this newly described disorder will continue to evolve.
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, 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.
Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies
MedGen UID:
1375601
Concept ID:
C4479520
Disease or Syndrome
IDDFSDA is an autosomal recessive severe multisystem disorder characterized by poor overall growth, developmental delay, early-onset seizures, intellectual disability, and dysmorphic features. There is phenotypic variability. The most severely affected patients have a neurodevelopmental disorder with microcephaly, absent speech, and inability to walk, and they require feeding tubes. Some patients have congenital heart defects or nonspecific abnormalities on brain imaging. Less severely affected individuals have mild to moderate intellectual disability with normal speech and motor development (summary by Santiago-Sim 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.
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.
Congenital heart defects and skeletal malformations syndrome
MedGen UID:
1618340
Concept ID:
C4539857
Disease or Syndrome
Congenital heart defects and skeletal malformations syndrome (CHDSKM) is characterized by atrial and ventricular septal defects, with aortic root dilation in adulthood. Skeletal defects are variable and include pectus excavatum, scoliosis, and finger contractures, and some patients exhibit joint laxity. Failure to thrive is observed during infancy and early childhood (Wang et al., 2017).
Intellectual disability, autosomal dominant 51
MedGen UID:
1625009
Concept ID:
C4540474
Mental or Behavioral Dysfunction
Intellectual disability, autosomal dominant 52
MedGen UID:
1615839
Concept ID:
C4540478
Mental or Behavioral Dysfunction
Intellectual disability, autosomal dominant 54
MedGen UID:
1614787
Concept ID:
C4540484
Mental or Behavioral Dysfunction
Proteasome-associated autoinflammatory syndrome 1
MedGen UID:
1648310
Concept ID:
C4746851
Disease or Syndrome
Proteasome-associated autoinflammatory syndrome-1 (PRAAS1) is an autosomal recessive disorder characterized by early childhood onset of annular erythematous plaques on the face and extremities with subsequent development of partial lipodystrophy and laboratory evidence of immune dysregulation. More variable features include recurrent fever, severe joint contractures, muscle weakness and atrophy, hepatosplenomegaly, basal ganglia calcifications, and microcytic anemia (summary by Agarwal et al., 2010; Kitamura et al., 2011; Arima et al., 2011). This disorder encompasses Nakajo-Nishimura syndrome (NKJO); joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome); and chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE). Among Japanese patients, this disorder is best described as Nakajo-Nishimura syndrome, since both Nakajo (1939) and Nishimura et al. (1950) contributed to the original phenotypic descriptions. Genetic Heterogeneity of Proteasome-Associated Autoinflammatory Syndrome See also PRAAS2 (618048), caused by mutation in the POMP gene (613386) on chromosome 13q12; PRAAS3 (617591), caused by mutation in the PSMB4 gene (602177) on chromosome 1q21; PRAAS4 (619183), caused by mutation in the PSMG2 gene (609702) on chromosome 18p11; PRAAS5 (619175), caused by mutation in the PSMB10 gene (176847) on chromosome 16q22; and PRAAS6 (620796), caused by mutation in the PSMB9 gene (177045) on chromosome 6p21.
Intellectual developmental disorder with or without epilepsy or cerebellar ataxia
MedGen UID:
1648354
Concept ID:
C4748041
Disease or Syndrome
Neurodevelopmental disorder with spasticity and poor growth
MedGen UID:
1648309
Concept ID:
C4748081
Disease or Syndrome
Neurodevelopmental disorder with spasticity and poor growth (NEDSG) is an autosomal recessive disorder characterized by severe early-onset encephalopathy with progressive microcephaly (Nahorski et al., 2018).
Menke-Hennekam syndrome 1
MedGen UID:
1675629
Concept ID:
C5193034
Disease or Syndrome
Menke-Hennekam syndrome-1 (MKHK1) is a congenital disorder characterized by variable impairment of intellectual development and facial dysmorphisms. Feeding difficulties, autistic behavior, recurrent upper airway infections, hearing impairment, short stature, and microcephaly are also frequently seen. Although mutations in the same gene cause Rubinstein-Taybi syndrome-1 (RSTS1; 180849), patients with MKHK1 do not resemble the striking phenotype of RSTS1. Genetic Heterogeneity of Menke-Hennekam Syndrome Menke-Hennekam syndrome-2 (MKHK2; 618333) is caused by heterozygous mutation in exons 30 or 31 of the EP300 gene (602700). Mutation elsewhere in that gene results in RSTS2 (613684).
Menke-Hennekam syndrome 2
MedGen UID:
1676668
Concept ID:
C5193035
Disease or Syndrome
Menke-Hennekam syndrome-2 (MKHK2) is a congenital disorder characterized by variable impairment of intellectual development and facial dysmorphisms. Feeding difficulties, autistic behavior, recurrent upper airway infections, and hearing impairment are also frequently seen. Although mutations in the same gene cause Rubinstein-Taybi syndrome-2 (RSTS2; 613684), patients with MKHK1 do not resemble the striking phenotype of RSTS2. For a discussion of genetic heterogeneity of Menke-Hennekam syndrome, see MKHK1 (618332).
Turnpenny-fry syndrome
MedGen UID:
1683283
Concept ID:
C5193060
Disease or Syndrome
Turnpenny-Fry syndrome (TPFS) is characterized by developmental delay, impaired intellectual development, impaired growth, and recognizable facial features that include frontal bossing, sparse hair, malar hypoplasia, small palpebral fissures and oral stoma, and dysplastic 'satyr' ears. Other common findings include feeding problems, constipation, and a range of brain, cardiac, vascular, and skeletal malformations (Turnpenny et al., 2018).
Basilicata-Akhtar syndrome
MedGen UID:
1684820
Concept ID:
C5231394
Disease or Syndrome
Basilicata-Akhtar syndrome (MRXSBA) is characterized by global developmental delay apparent from infancy, feeding difficulties, hypotonia, and poor or absent speech. Most patients are able to walk, although they may have an unsteady gait or spasticity. Additional findings include dysmorphic facial features and mild distal skeletal anomalies. Males and females are similarly affected (summary by Basilicata et al., 2018).
Intellectual developmental disorder 61
MedGen UID:
1684867
Concept ID:
C5231400
Disease or Syndrome
Autosomal dominant intellectual developmental disorder-61 (MRD61) is characterized by global developmental delay apparent in infancy with mildly impaired intellectual development, expressive speech delay, and behavioral abnormalities, including autism spectrum disorder and attention deficit-hyperactivity disorder (ADHD). Most affected individuals learn to walk on time or with some mild delay. Additional features are highly variable and may include nonspecific dysmorphic features, obstipation, ocular anomalies, and poor overall growth (Snijders Blok et al., 2018).
Neurodevelopmental disorder with absent language and variable seizures
MedGen UID:
1684803
Concept ID:
C5231469
Disease or Syndrome
Developmental and epileptic encephalopathy, 83
MedGen UID:
1684784
Concept ID:
C5231487
Disease or Syndrome
Developmental and epileptic encephalopathy-83 (DEE83) is a severe autosomal recessive neurodevelopmental disorder characterized by onset of frequent seizures in the first days to months of life that are usually refractory to medical treatment and are associated with significant EEG abnormalities. Affected individuals have profoundly impaired development, with no motor or language skill acquisition, poor or absent visual tracking, and poor oromotor function necessitating tube feeding. Many patients die in the first years of life (summary by Perenthaler et al., 2020). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Intellectual developmental disorder, autosomal dominant 63, with macrocephaly
MedGen UID:
1716581
Concept ID:
C5394205
Disease or Syndrome
Neurodevelopmental disorder with relative macrocephaly and with or without cardiac or endocrine anomalies
MedGen UID:
1714169
Concept ID:
C5394221
Disease or Syndrome
Nabais Sa-de Vries syndrome type 2 (NSDVS2) is characterized by global developmental delay apparent from birth and distinctive dysmorphic facial features. Most patients have additional anomalies, including congenital heart defects, sleep disturbances, hypotonia, and variable endocrine abnormalities, such as hypothyroidism (summary by Nabais Sa 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).
Deeah syndrome
MedGen UID:
1756624
Concept ID:
C5436579
Disease or Syndrome
DEEAH syndrome is an autosomal recessive multisystemic disorder with onset in early infancy. Affected individuals usually present in the perinatal period with respiratory insufficiency, apneic episodes, and generalized hypotonia. The patients have failure to thrive and severely impaired global development with poor acquisition of motor, cognitive, and language skills. Other common features include endocrine, pancreatic exocrine, and autonomic dysfunction, as well as hematologic disturbances, mainly low hemoglobin. Patients also have dysmorphic and myopathic facial features. Additional more variable features include seizures, undescended testes, and distal skeletal anomalies. Death in early childhood may occur (summary by Schneeberger et al., 2020).
Neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia
MedGen UID:
1776912
Concept ID:
C5436585
Disease or Syndrome
Neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia (NEDDISH) is an autosomal recessive disorder characterized by global developmental delay and mildly to severely impaired intellectual development with poor speech and language acquisition. Some patients may have early normal development with onset of the disorder in the first years of life. More variable neurologic abnormalities include hypotonia, seizures, apnea, mild signs of autonomic or peripheral neuropathy, and autism. Aside from dysmorphic facial features and occasional findings such as scoliosis or undescended testes, other organ systems are not involved (summary by Schneeberger et al., 2020).
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).
Leukodystrophy, hypomyelinating, 20
MedGen UID:
1765130
Concept ID:
C5436730
Disease or Syndrome
Hypomyelinating leukodystrophy-20 (HLD20) is an autosomal recessive neurodegenerative disorder characterized by the loss of developmental milestones at about 12 to 16 months of age after normal early development. Patients lose motor, language, and cognitive skills and show poor overall growth with microcephaly. The disorder is progressive, resulting in feeding difficulties and spastic quadriplegia. Some patients may have seizures. Brain imaging shows subcortical white matter abnormalities and a thin corpus callosum, suggesting a myelination defect. Death usually occurs in childhood (Al-Abdi et al., 2020). For a discussion of genetic heterogeneity of HLD, see 312080.
Kilquist syndrome
MedGen UID:
1742639
Concept ID:
C5436756
Disease or Syndrome
Kilquist syndrome (KILQS) is an autosomal recessive multisystem disorder characterized by neurologic, gastrointestinal, and secretory dysfunction. Affected individuals present at birth with hypotonia, feeding difficulties, mild dysmorphic features, and sensorineural hearing loss. They show poor overall growth associated with gastrointestinal anomalies such as gastroesophageal reflux or midgut malrotation, as well as profound global developmental delay with inability to sit or speak. Tear, sweat, and saliva production is also impaired, causing dry mouth and recurrent bronchial mucus plugging. Some of the clinical features are reminiscent of cystic fibrosis (CF; 219700) (summary by Stodberg et al., 2020).
Coffin-Siris syndrome 12
MedGen UID:
1782096
Concept ID:
C5444111
Disease or Syndrome
Coffin-Siris syndrome-12 (CSS12) is a neurodevelopmental disorder characterized by global developmental delay with variably impaired intellectual development, speech and language delay, and behavioral abnormalities, such as autism or hyperactivity. Affected individuals may have hypotonia and poor feeding in infancy. There are variable dysmorphic facial features, although most patients do not have the classic hypoplastic fifth digit/nail abnormalities that are often observed in other forms of CSS (Barish et al., 2020). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
Microcephaly 26, primary, autosomal dominant
MedGen UID:
1779629
Concept ID:
C5543048
Disease or Syndrome
Autosomal dominant primary microcephaly-26 (MCPH26) is characterized by progressive microcephaly beginning at birth and associated with global developmental delay with variably impaired intellectual development. Some patients may have only mild learning difficulties or speech delay, whereas other are more severely affected with the inability to walk or speak. Additional features may include short stature, spasticity, feeding difficulties requiring tube feeding, and nonspecific dysmorphic facial features. Brain imaging in some patients shows a simplified gyral pattern or dysgenesis of the corpus callosum, suggesting abnormal neuronal migration (summary by Cristofoli et al., 2020). For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200).
Microcephaly 27, primary, autosomal dominant
MedGen UID:
1783457
Concept ID:
C5543051
Disease or Syndrome
Autosomal dominant primary microcephaly-27 (MCPH27) is characterized by small head circumference apparent in early childhood and associated with global developmental delay manifest as delayed walking, inability to walk, impaired intellectual development, and poor or absent speech. Most patients have variable and nonspecific additional features, including facial dysmorphism, hypotonia, limb hypertonia, poor feeding, and distal skeletal anomalies. Brain imaging may show enlarged ventricles or gyral abnormalities, but most have normal imaging (Parry et al., 2021). For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200).
Intellectual developmental disorder, autosomal dominant 64
MedGen UID:
1784554
Concept ID:
C5543067
Disease or Syndrome
Autosomal dominant intellectual developmental disorder-64 (MRD64) is characterized by mildly to severely impaired intellectual development (ID) with speech delays. Most patients also have autism spectrum disorder (ASD). Additional features are highly variable but may include motor delay, attention deficit-hyperactivity disorder (ADHD), and nonspecific dysmorphic features (summary by Mirzaa et al., 2020).
Neurofacioskeletal syndrome with or without renal agenesis
MedGen UID:
1778926
Concept ID:
C5543070
Disease or Syndrome
Neurofacioskeletal syndrome with or without renal agenesis (NFSRA) is characterized by developmental delay and/or intellectual disability; corpus callosum hypoplasia or agenesis; facial dysmorphism, including upslanting palpebral fissures, broad nasal tip, and wide mouth; and skeletal abnormalities, including short stature, scoliosis, and flexion contractures, with broad fingertips and/or toes. Renal agenesis, unilateral or bilateral, has also been observed in some patients (Schneeberger et al., 2020).
KINSSHIP syndrome
MedGen UID:
1779339
Concept ID:
C5543317
Disease or Syndrome
KINSSHIP syndrome (KINS) is an autosomal dominant disorder characterized by a recognizable pattern of anomalies including developmental delay, impaired intellectual development, seizures, mesomelic dysplasia, dysmorphic facial features, horseshoe or hypoplastic kidney, and failure to thrive (summary by Voisin et al., 2021).
CATARACTS, SPASTIC PARAPARESIS, AND SPEECH DELAY
MedGen UID:
1778818
Concept ID:
C5543440
Disease or Syndrome
Cataracts, spastic paraparesis, and speech delay (CSPSD) is an autosomal dominant disorder characterized by spastic paraparesis and bilateral congenital/juvenile cataracts. Speech delay is a common feature (Ferdinandusse et al., 2021).
Visceral myopathy 2
MedGen UID:
1783630
Concept ID:
C5543466
Disease or Syndrome
Visceral myopathy-2 (VSCM2) is characterized by gastrointestinal symptoms resulting from intestinal dysmotility and paresis, including abdominal distention, pain, nausea, and vomiting. Some patients exhibit predominantly esophageal symptoms, with hiatal hernia and severe reflux resulting in esophagitis and stricture, whereas others experience chronic intestinal pseudoobstruction. Bladder involvement resulting in megacystis and megaureter has also been observed and may be evident at birth (Dong et al., 2019; Gilbert et al. (2020)).
Ataxia, intention tremor, and hypotonia syndrome, childhood-onset
MedGen UID:
1787902
Concept ID:
C5543478
Disease or Syndrome
Childhood-onset ataxia, intention tremor, and hypotonia syndrome (ATITHS) is a neurodevelopmental disorder characterized by delayed walking due to ataxia, intention tremor, and hypotonia apparent from early childhood. Affected individuals have global developmental delay with mildly impaired intellectual development and speech delay or learning disabilities. Eye movement abnormalities may also be present. Brain imaging shows cerebellar atrophy in some patients (summary by Webb et al., 2021).
Faundes-Banka syndrome
MedGen UID:
1782083
Concept ID:
C5543554
Disease or Syndrome
Faundes-Banka syndrome (FABAS) is an autosomal dominant disorder characterized by variable combinations of developmental delay and microcephaly, as well as micrognathia and other dysmorphic features (Faundes et al., 2021).
Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities
MedGen UID:
1780615
Concept ID:
C5543591
Disease or Syndrome
Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities (NEDHFBA) is an autosomal recessive neurologic syndrome characterized by global developmental delay with severely impaired intellectual development, hypotonia and muscle weakness, often resulting in the inability to walk or sit, and characteristic coarse facial features. Additional features include feeding difficulties, respiratory distress, scoliosis, poor visual function, and rotary nystagmus. Brain imaging shows variable abnormalities, including enlarged ventricles, decreased white matter volume, white matter changes, thin corpus callosum, and cerebellar hypoplasia (summary by Loddo et al., 2020).
Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum
MedGen UID:
1790413
Concept ID:
C5551361
Disease or Syndrome
Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum (NEDDFAC) is characterized by global developmental delay, impaired intellectual development with poor or absent speech and language, and dysmorphic facial features. Brain imaging tends to show thin corpus callosum and decreased white matter volume. Additional features such as seizures, cardiac defects, and behavioral abnormalities may also occur. The phenotype is variable (summary by Bina et al., 2020).
Intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies
MedGen UID:
1794140
Concept ID:
C5561930
Disease or Syndrome
X-linked syndromic intellectual developmental disorder with pigmentary mosaicism and coarse facies (MRXSPF) is characterized by a phenotypic triad of severe developmental delay, coarse facial dysmorphisms, and Blaschkoid pigmentary mosaicism. Additional clinical features may include epilepsy, orthopedic abnormalities, hypotonia, and growth abnormalities. The disorder affects both males and females (Villegas et al., 2019; Diaz et al., 2020).
Focal segmental glomerulosclerosis and neurodevelopmental syndrome
MedGen UID:
1794148
Concept ID:
C5561938
Disease or Syndrome
Focal segmental glomerulosclerosis and neurodevelopmental syndrome (FSGSNEDS) is characterized by global developmental delay and renal dysfunction manifest as proteinuria and nephrotic syndrome apparent from infancy or early childhood. Some patients present with renal disease, whereas others present with developmental delay and develop renal disease later in childhood. Renal biopsy shows focal segmental glomerulosclerosis (FSGS), but the course of the disease is variable: some patients have transient proteinuria and others require renal transplant. Neurodevelopmental features are also variable, with some patients having only mildly impaired intellectual development, and others having a severe developmental disorder associated with early-onset refractory seizures or epileptic encephalopathy. Additional features, including feeding difficulties, poor overall growth, and nonspecific dysmorphic facial features, are commonly observed (summary by Assoum et al., 2018 and Weng et al., 2021).
Visceral neuropathy, familial, 2, autosomal recessive
MedGen UID:
1794160
Concept ID:
C5561950
Disease or Syndrome
Autosomal recessive visceral neuropathy-2 (VSCN2) is characterized by intestinal dysmotility due to aganglionosis or hypoganglionosis of the colon. Patients also exhibit peripheral axonal neuropathy, ptosis, and sensorineural hearing loss (Le et al., 2021). For a discussion of genetic heterogeneity of VSCN, see VSCN1 (243180).
VISS syndrome
MedGen UID:
1794165
Concept ID:
C5561955
Disease or Syndrome
VISS syndrome is a generalized connective tissue disorder characterized by early-onset thoracic aortic aneurysm and other connective tissue findings, such as aneurysm and tortuosity of other arteries, joint hypermobility, skin laxity, and hernias, as well as craniofacial dysmorphic features, structural cardiac defects, skeletal anomalies, and motor developmental delay (Van Gucht et al., 2021). Immune dysregulation has been observed in some patients (Ziegler et al., 2021).
Central hypoventilation syndrome, congenital, 2, and autonomic dysfunction
MedGen UID:
1794173
Concept ID:
C5561963
Disease or Syndrome
Congenital central hypoventilation syndrome-2 and autonomic dysfunction (CCHS2) is an autosomal recessive disorder characterized by shallow breathing and apneic spells apparent in the neonatal period. Affected infants require mechanical ventilation due to impaired ventilatory response to hypercapnia, as well as tube feeding due to poor swallowing, aspiration, and gastrointestinal dysmotility. Some patients have other features of autonomic dysfunction, including bladder dysfunction, sinus bradycardia, and temperature dysregulation. Although mild global developmental delay with learning difficulties and seizures were present in the single family reported, it was unclear if these features were related to the hypoventilation phenotype (Spielmann et al., 2017). For a discussion of genetic heterogeneity of CCHS, see CCHS1 (209880).
Central hypoventilation syndrome, congenital, 3
MedGen UID:
1794174
Concept ID:
C5561964
Disease or Syndrome
Congenital central hypoventilation syndrome-3 (CCHS3) is an autosomal recessive disorder characterized by slow and shallow breathing due to a deficiency in autonomic control of respiration. Affected individuals present in the neonatal period with respiratory insufficiency and absence of the hypercapnic reflex that stimulates breathing. Patients also have gastrointestinal problems manifest as feeding difficulties and diarrhea or constipation. Other features may include poor heat tolerance and paroxysmal hypertension (Hernandez-Miranda et al., 2018). For a discussion of genetic heterogeneity of CCHS, see CCHS1 (209880).
Neurodevelopmental disorder with hypotonia and dysmorphic facies
MedGen UID:
1794184
Concept ID:
C5561974
Disease or Syndrome
Neurodevelopmental disorder with hypotonia and dysmorphic facies (NEDHYDF) is characterized by global developmental delay and hypotonia apparent from birth. Affected individuals have variably impaired intellectual development, often with speech delay and delayed walking. Seizures are generally not observed, although some patients may have single seizures or late-onset epilepsy. Most patients have prominent dysmorphic facial features. Additional features may include congenital cardiac defects (without arrhythmia), nonspecific renal anomalies, joint contractures or joint hyperextensibility, dry skin, and cryptorchidism. There is significant phenotypic variability in both the neurologic and extraneurologic manifestations (summary by Tan et al., 2022).
Developmental delay with or without intellectual impairment or behavioral abnormalities
MedGen UID:
1794214
Concept ID:
C5562004
Disease or Syndrome
Developmental delay with or without intellectual impairment or behavioral abnormalities (DDIB) is an autosomal dominant disorder with a nonspecific phenotype of developmental delay. Additional features may include neonatal feeding problems, hypotonia, and dysmorphic facial features (Dulovic-Mahlow et al., 2019; van Woerden et al., 2021).
Acromesomelic dysplasia 4
MedGen UID:
1794238
Concept ID:
C5562028
Disease or Syndrome
Acromesomelic dysplasia-4 (AMD4) is characterized by disproportionate short stature due to mesomelic shortening of the limbs. Radiographic hallmarks include mild to moderate platyspondyly, moderate brachydactyly, iliac flaring, and metaphyseal alterations of the long bones that progressively increase with age (Diaz-Gonzalez et al., 2022). For a discussion of genetic heterogeneity of acromesomelic dysplasia, see AMD1 (602875).
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).
Central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease
MedGen UID:
1794285
Concept ID:
C5562075
Disease or Syndrome
Congenital central hypoventilation syndrome (CCHS) represents the extreme manifestation of autonomic nervous system dysregulation (ANSD) with the hallmark of disordered respiratory control. The age of initial recognition of CCHS ranges from neonatal onset (i.e., in the first 30 days of life) to (less commonly) later onset (from 1 month to adulthood). Neonatal-onset CCHS is characterized by apparent hypoventilation with monotonous respiratory rates and shallow breathing either during sleep only or while awake as well as asleep; ANSD including decreased heart rate beat-to-beat variability and sinus pauses; altered temperature regulation; and altered pupillary response to light. Some children have altered development of neural crest-derived structures (i.e., Hirschsprung disease, altered esophageal motility/dysphagia, and severe constipation even in the absence of Hirschsprung disease) and/or tumors of neural crest origin (neuroblastoma, ganglioneuroma, and ganglioneuroblastoma). Neurocognitive delay is variable, and possibly influenced by cyanotic breath holding, prolonged sinus pauses, need for 24-hour/day artificial ventilation, and seizures. Later-onset CCHS is characterized by alveolar hypoventilation during sleep and attenuated manifestations of ANSD.
Combined oxidative phosphorylation defect type 25
MedGen UID:
1799165
Concept ID:
C5567742
Disease or Syndrome
A rare mitochondrial oxidative phosphorylation disorder with decreased respiratory complex I and IV enzyme activity. Characteristics of this disease hypotonia, global developmental delay, neonatal onset of progressive pectus carinatum without other skeletal abnormalities, poor growth, sensorineural hearing loss, dysmorphic features and brain abnormalities such as cerebral atrophy, quadriventricular dilatation and thin corpus callosum posteriorly.
Autoinflammatory syndrome, familial, X-linked, Behcet-like 2
MedGen UID:
1808082
Concept ID:
C5575495
Disease or Syndrome
X-linked familial Behcet-like autoinflammatory syndrome-2 (AIFBL2) is an X-linked recessive disorder characterized by the onset of inflammatory symptoms in the first decade of life in male patients. Affected males often present with oral mucosal ulceration and skin inflammation. More variable features may include gastrointestinal ulceration, arthritis, recurrent fevers, and iron deficiency anemia. Laboratory studies are consistent with immune dysregulation manifest as increased inflammatory markers and variable immune cell abnormalities, such as decreased NK cells and low memory B cells. One patient presented with recurrent infections and immunodeficiency in addition to autoinflammation. The disorder results from a defect in ELF4, which normally acts as a negative regulator of inflammatory disease. Symptoms may respond to blockade of IL1 (see 147760) or TNFA (191160) (summary by Tyler et al., 2021 and Sun et al., 2022). For a discussion of genetic heterogeneity of AIFBL, see AIFBL1 (616744).
Knobloch syndrome 2
MedGen UID:
1812153
Concept ID:
C5676897
Disease or Syndrome
Bryant-Li-Bhoj neurodevelopmental syndrome 1
MedGen UID:
1801103
Concept ID:
C5676905
Disease or Syndrome
Bryant-Li-Bhoj neurodevelopmental syndrome-1 (BRYLIB1) is a highly variable phenotype characterized predominantly by moderate to severe global developmental delay with impaired intellectual development, poor or absent speech, and delayed motor milestones. Most patients have hypotonia, although some have peripheral hypertonia. Common features include abnormal head shape, variable dysmorphic facial features, oculomotor abnormalities, feeding problems, and nonspecific brain imaging abnormalities. Additional features may include hearing loss, seizures, short stature, and mild skeletal defects (summary by Bryant et al., 2020). Genetic Heterogeneity of Bryant-Li-Bhoj Neurodevelopmental Syndrome See also BRYLIB2 (619721), caused by heterozygous mutation in the H3F3B gene (601058).
Bryant-Li-Bhoj neurodevelopmental syndrome 2
MedGen UID:
1811435
Concept ID:
C5676906
Disease or Syndrome
Bryant-Li-Bhoj neurodevelopmental syndrome-2 (BRYLIB2) is a highly variable phenotype characterized predominantly by moderate to severe global developmental delay with impaired intellectual development, poor or absent speech, and delayed motor milestones. Most patients have hypotonia, although some have peripheral hypertonia. Common features include variable dysmorphic facial features, oculomotor abnormalities, feeding problems, and nonspecific brain imaging abnormalities. Additional features may include hearing loss, seizures, short stature, and mild skeletal defects (summary by Bryant et al., 2020). For a discussion of genetic heterogeneity of Bryant-Li-Bhoj neurodevelopmental syndrome, see BRYLIB1 (619720).
Developmental and epileptic encephalopathy 100
MedGen UID:
1809351
Concept ID:
C5676932
Disease or Syndrome
Developmental and epileptic encephalopathy-100 (DEE100) is a severe neurologic disorder characterized by global developmental delay and onset of variable types of seizures in the first months or years of life. Most patients have refractory seizures and show developmental regression after seizure onset. Affected individuals have ataxic gait or inability to walk and severe to profoundly impaired intellectual development, often with absent speech. Additional more variable features may include axial hypotonia, hyperkinetic movements, dysmorphic facial features, and brain imaging abnormalities (summary by Schneider et al., 2021). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Developmental and epileptic encephalopathy 102
MedGen UID:
1812769
Concept ID:
C5676991
Disease or Syndrome
Developmental and epileptic encephalopathy-102 (DEE102) is an autosomal recessive neurodevelopmental disorder characterized by global developmental delay and severe to profoundly impaired intellectual development with inability to walk or speak. Most patients have onset of variable types of seizures within the first year of life, and the seizures tend to be refractory. Additional features include progressive microcephaly, visual impairment, axial hypotonia, peripheral hypertonia, and nonspecific brain imaging abnormalities (Marafi et al., 2022). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Intellectual developmental disorder, autosomal recessive 76
MedGen UID:
1808571
Concept ID:
C5677007
Mental or Behavioral Dysfunction
Autosomal recessive intellectual developmental disorder-76 (MRT76) is characterized by impaired intellectual development, absent speech, poor sleep, abnormal EEG with seizures, normal brain imaging, and precocious puberty (Ismail 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.
Chromosome Xq13 duplication syndrome
MedGen UID:
1809227
Concept ID:
C5677057
Disease or Syndrome
Neurodevelopmental disorder with gait disturbance, dysmorphic facies, and behavioral abnormalities, X-linked
MedGen UID:
1823953
Concept ID:
C5774179
Disease or Syndrome
Hijazi-Reis syndrome (HIJRS) is an X-linked dominant disorder characterized by global developmental delay with hypotonia, motor delay, impaired intellectual development, and speech and language delay. Affected individuals also have dysmorphic facial features, gastrointestinal issues, and ocular anomalies. Rare patients have seizures (Hijazi et al., 2022).
Hyperinsulinemic hypoglycemia, familial, 8
MedGen UID:
1824072
Concept ID:
C5774299
Disease or Syndrome
Familial hyperinsulinemic hypoglycemia-8 (HHF8) is an autosomal recessive disorder characterized by protein-related hypoglycemia and persistent mild hyperammonemia (summary by Shahroor et al., 2022). For a phenotypic description and a discussion of genetic heterogeneity of familial hyperinsulinemic hypoglycemia, see HHF1 (256450).
Tessadori-Van Haaften neurodevelopmental syndrome 3
MedGen UID:
1824083
Concept ID:
C5774310
Disease or Syndrome
Tessadori-Bicknell-van Haaften neurodevelopmental syndrome-3 (TEBIVANED3) is characterized by global developmental delay with poor overall growth, impaired intellectual development, and speech difficulties. More variable features include hypotonia, microcephaly, and dysmorphic facies. The severity and manifestations of the disorder are highly variable (Tessadori et al., 2022). For a discussion of genetic heterogeneity of Tessadori-Bicknell-van Haaften neurodevelopmental disorder, see TEBIVANED1 (619758).
Auriculocondylar syndrome 2B
MedGen UID:
1841300
Concept ID:
C5830664
Disease or Syndrome
ARCND2B is characterized by the typical features of auriculocondylar syndrome, including the pathognomonic question mark ears, consisting of a variable degree of clefting between the helix and earlobe, as well as hypoplasia of the mandibular condyle, temporomandibular joint abnormalities, micrognathia, microstomia, glossoptosis, and a round facial appearance with prominent cheeks. Patients have difficulty chewing, respiratory abnormalities, snoring, and obstructive and central apneas. In addition, they experience severe gastrointestinal problems, including feeding difficulties with failure to thrive, gastroesophageal reflux, and chronic constipation, and male patients show macropenis whereas female patients may exhibit clitoromegaly (summary by Leoni et al., 2016). Heterozygous mutation in the PLCB4 gene also causes an autosomal dominant form of auriculocondylar syndrome (see ARCND2A, 614669). For a discussion of genetic heterogeneity of auriculocondylar syndrome, see ARCND1 (602483).

Professional guidelines

PubMed

Camilleri M
JAMA 2021 Mar 2;325(9):865-877. doi: 10.1001/jama.2020.22532. PMID: 33651094
Bharucha AE, Lacy BE
Gastroenterology 2020 Apr;158(5):1232-1249.e3. Epub 2020 Jan 13 doi: 10.1053/j.gastro.2019.12.034. PMID: 31945360Free PMC Article
Aziz I, Whitehead WE, Palsson OS, Törnblom H, Simrén M
Expert Rev Gastroenterol Hepatol 2020 Jan;14(1):39-46. Epub 2020 Jan 2 doi: 10.1080/17474124.2020.1708718. PMID: 31893959

Recent clinical studies

Etiology

Classen M, Righini-Grunder F, Schumann S, Gontard AV, Laffolie J
Dtsch Arztebl Int 2022 Oct 14;119(41):697-708. doi: 10.3238/arztebl.m2022.0309. PMID: 36261928Free PMC Article
Ho JMD, How CH
Singapore Med J 2020 Feb;61(2):63-68. doi: 10.11622/smedj.2020014. PMID: 32152637Free PMC Article
Serra J, Pohl D, Azpiroz F, Chiarioni G, Ducrotté P, Gourcerol G, Hungin APS, Layer P, Mendive JM, Pfeifer J, Rogler G, Scott SM, Simrén M, Whorwell P; Functional Constipation Guidelines Working Group
Neurogastroenterol Motil 2020 Feb;32(2):e13762. Epub 2019 Nov 22 doi: 10.1111/nmo.13762. PMID: 31756783
Sharma A, Rao S
Handb Exp Pharmacol 2017;239:59-74. doi: 10.1007/164_2016_111. PMID: 28185025
Rao SS, Rattanakovit K, Patcharatrakul T
Nat Rev Gastroenterol Hepatol 2016 May;13(5):295-305. Epub 2016 Apr 1 doi: 10.1038/nrgastro.2016.53. PMID: 27033126

Diagnosis

Bellini M, Tonarelli S, Barracca F, Rettura F, Pancetti A, Ceccarelli L, Ricchiuti A, Costa F, de Bortoli N, Marchi S, Rossi A
Nutrients 2021 Sep 26;13(10) doi: 10.3390/nu13103386. PMID: 34684388Free PMC Article
Bharucha AE, Lacy BE
Gastroenterology 2020 Apr;158(5):1232-1249.e3. Epub 2020 Jan 13 doi: 10.1053/j.gastro.2019.12.034. PMID: 31945360Free PMC Article
Aziz I, Whitehead WE, Palsson OS, Törnblom H, Simrén M
Expert Rev Gastroenterol Hepatol 2020 Jan;14(1):39-46. Epub 2020 Jan 2 doi: 10.1080/17474124.2020.1708718. PMID: 31893959
Forootan M, Bagheri N, Darvishi M
Medicine (Baltimore) 2018 May;97(20):e10631. doi: 10.1097/MD.0000000000010631. PMID: 29768326Free PMC Article
Camilleri M, Ford AC, Mawe GM, Dinning PG, Rao SS, Chey WD, Simrén M, Lembo A, Young-Fadok TM, Chang L
Nat Rev Dis Primers 2017 Dec 14;3:17095. doi: 10.1038/nrdp.2017.95. PMID: 29239347

Therapy

Naseer M, Poola S, Uraz S, Tahan V
Curr Clin Pharmacol 2020;15(3):207-215. doi: 10.2174/1574884715666200212125035. PMID: 32048977
Aziz I, Whitehead WE, Palsson OS, Törnblom H, Simrén M
Expert Rev Gastroenterol Hepatol 2020 Jan;14(1):39-46. Epub 2020 Jan 2 doi: 10.1080/17474124.2020.1708718. PMID: 31893959
Raetz J, Wilson M, Collins K
Am Fam Physician 2019 Jun 1;99(11):682-688. PMID: 31150188
Camilleri M, Ford AC, Mawe GM, Dinning PG, Rao SS, Chey WD, Simrén M, Lembo A, Young-Fadok TM, Chang L
Nat Rev Dis Primers 2017 Dec 14;3:17095. doi: 10.1038/nrdp.2017.95. PMID: 29239347
Müller-Lissner SA, Kamm MA, Scarpignato C, Wald A
Am J Gastroenterol 2005 Jan;100(1):232-42. doi: 10.1111/j.1572-0241.2005.40885.x. PMID: 15654804

Prognosis

Rajindrajith S, Devanarayana NM, Thapar N, Benninga MA
Eur J Pediatr 2023 Apr;182(4):1447-1458. Epub 2023 Jan 23 doi: 10.1007/s00431-023-04821-8. PMID: 36689003
Staller K
J Clin Gastroenterol 2018 Jul;52(6):490-501. doi: 10.1097/MCG.0000000000001049. PMID: 29794543
Liu Z, Yan S, Wu J, He L, Li N, Dong G, Fang J, Fu W, Fu L, Sun J, Wang L, Wang S, Yang J, Zhang H, Zhang J, Zhao J, Zhou W, Zhou Z, Ai Y, Zhou K, Liu J, Xu H, Cai Y, Liu B
Ann Intern Med 2016 Dec 6;165(11):761-769. Epub 2016 Sep 13 doi: 10.7326/M15-3118. PMID: 27618593
Gfroerer S, Rolle U
World J Gastroenterol 2015 Sep 7;21(33):9683-7. doi: 10.3748/wjg.v21.i33.9683. PMID: 26361414Free PMC Article
Dinning PG, Di Lorenzo C
Best Pract Res Clin Gastroenterol 2011 Feb;25(1):89-101. doi: 10.1016/j.bpg.2010.12.006. PMID: 21382581

Clinical prediction guides

van der Schoot A, Helander C, Whelan K, Dimidi E
Clin Nutr 2022 Dec;41(12):2759-2777. Epub 2022 Oct 27 doi: 10.1016/j.clnu.2022.10.015. PMID: 36372047
Doğan İG, Gürşen C, Akbayrak T, Balaban YH, Vahabov C, Üzelpasacı E, Özgül S
Phys Ther 2022 Jul 4;102(7) doi: 10.1093/ptj/pzac058. PMID: 35554601
Corsetti M, Landes S, Lange R
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