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Tall stature

MedGen UID:
69137
Concept ID:
C0241240
Finding
Synonyms: Accelerated linear growth; Increased linear growth
SNOMED CT: Tall stature (248328003); Large stature (248328003)
 
HPO: HP:0000098

Definition

A height above that which is expected according to age and gender norms. [from HPO]

Conditions with this feature

Marfan syndrome
MedGen UID:
44287
Concept ID:
C0024796
Disease or Syndrome
FBN1-related Marfan syndrome (Marfan syndrome), a systemic disorder of connective tissue with a high degree of clinical variability, comprises a broad phenotypic continuum ranging from mild (features of Marfan syndrome in one or a few systems) to severe and rapidly progressive neonatal multiorgan disease. Cardinal manifestations involve the ocular, skeletal, and cardiovascular systems. Ocular findings include myopia (>50% of affected individuals); ectopia lentis (seen in approximately 60% of affected individuals); and an increased risk for retinal detachment, glaucoma, and early cataracts. Skeletal system manifestations include bone overgrowth and joint laxity; disproportionately long extremities for the size of the trunk (dolichostenomelia); overgrowth of the ribs that can push the sternum in (pectus excavatum) or out (pectus carinatum); and scoliosis that ranges from mild to severe and progressive. The major morbidity and early mortality in Marfan syndrome relate to the cardiovascular system and include dilatation of the aorta at the level of the sinuses of Valsalva (predisposing to aortic tear and rupture), mitral valve prolapse with or without regurgitation, tricuspid valve prolapse, and enlargement of the proximal pulmonary artery. Severe and prolonged regurgitation of the mitral and/or aortic valve can predispose to left ventricular dysfunction and occasionally heart failure. With proper management, the life expectancy of someone with Marfan syndrome approximates that of the general population.
Sotos syndrome
MedGen UID:
61232
Concept ID:
C0175695
Disease or Syndrome
Sotos syndrome is characterized by a distinctive facial appearance (broad and prominent forehead with a dolichocephalic head shape, sparse frontotemporal hair, downslanting palpebral fissures, malar flushing, long and narrow face, long chin); learning disability (early developmental delay, mild-to-severe intellectual impairment); and overgrowth (height and/or head circumference =2 SD above the mean). These three clinical features are considered the cardinal features of Sotos syndrome. Major features of Sotos syndrome include behavioral problems (most notably autistic spectrum disorder), advanced bone age, cardiac anomalies, cranial MRI/CT abnormalities, joint hyperlaxity with or without pes planus, maternal preeclampsia, neonatal complications, renal anomalies, scoliosis, and seizures.
Marshall-Smith syndrome
MedGen UID:
75551
Concept ID:
C0265211
Disease or Syndrome
The Marshall-Smith syndrome (MRSHSS) is a malformation syndrome characterized by accelerated skeletal maturation, relative failure to thrive, respiratory difficulties, mental retardation, and unusual facies, including prominent forehead, shallow orbits, blue sclerae, depressed nasal bridge, and micrognathia (Adam et al., 2005).
Ehlers-Danlos syndrome, kyphoscoliotic type 1
MedGen UID:
75672
Concept ID:
C0268342
Disease or Syndrome
PLOD1-related kyphoscoliotic Ehlers-Danlos syndrome (kEDS) is an autosomal recessive generalized connective tissue disorder characterized by hypotonia, early-onset kyphoscoliosis, and generalized joint hypermobility in association with skin fragility and ocular abnormality. Intelligence is normal. Life span may be normal, but affected individuals are at risk for rupture of medium-sized arteries. Adults with severe kyphoscoliosis are at risk for complications from restrictive lung disease, recurrent pneumonia, and cardiac failure.
Gamma-aminobutyric acid transaminase deficiency
MedGen UID:
137977
Concept ID:
C0342708
Disease or Syndrome
GABA-transaminase deficiency is characterized by neonatal or early infantile-onset encephalopathy, hypotonia, hypersomnolence, epilepsy, choreoathetosis, and accelerated linear growth. Electroencephalograms show burst-suppression, modified hypsarrhythmia, multifocal spikes, and generalized spike-wave. Severity varies, but most patients have profound developmental impairment and some patients die in infancy (summary by Koenig et al., 2017).
Classic homocystinuria
MedGen UID:
199606
Concept ID:
C0751202
Disease or Syndrome
Homocystinuria caused by cystathionine ß-synthase (CBS) deficiency is characterized by involvement of the eye (ectopia lentis and/or severe myopia), skeletal system (excessive height, long limbs, scolioisis, and pectus excavatum), vascular system (thromboembolism), and CNS (developmental delay/intellectual disability). All four ? or only one ? of the systems can be involved; expressivity is variable for all of the clinical signs. It is not unusual for a previously asymptomatic individual to present in adult years with only a thromboembolic event that is often cerebrovascular. Two phenotypic variants are recognized, B6-responsive homocystinuria and B6-non-responsive homocystinuria. B6-responsive homocystinuria is usually milder than the non-responsive variant. Thromboembolism is the major cause of early death and morbidity. IQ in individuals with untreated homocystinuria ranges widely, from 10 to 138. In B6-responsive individuals the mean IQ is 79 versus 57 for those who are B6-non-responsive. Other features that may occur include: seizures, psychiatric problems, extrapyramidal signs (e.g., dystonia), hypopigmentation of the skin and hair, malar flush, livedo reticularis, and pancreatitis.
X-linked intellectual disability with marfanoid habitus
MedGen UID:
167096
Concept ID:
C0796022
Disease or Syndrome
MED12-related disorders include the phenotypes of FG syndrome type 1 (FGS1), Lujan syndrome (LS), X-linked Ohdo syndrome (XLOS), Hardikar syndrome (HS), and nonspecific intellectual disability (NSID). FGS1 and LS share the clinical findings of cognitive impairment, hypotonia, and abnormalities of the corpus callosum. FGS1 is further characterized by absolute or relative macrocephaly, tall forehead, downslanted palpebral fissures, small and simple ears, constipation and/or anal anomalies, broad thumbs and halluces, and characteristic behavior. LS is further characterized by large head, tall thin body habitus, long thin face, prominent nasal bridge, high narrow palate, and short philtrum. Carrier females in families with FGS1 and LS are typically unaffected. XLOS is characterized by intellectual disability, blepharophimosis, and facial coarsening. HS has been described in females with cleft lip and/or cleft palate, biliary and liver anomalies, intestinal malrotation, pigmentary retinopathy, and coarctation of the aorta. Developmental and cognitive concerns have not been reported in females with HS. Pathogenic variants in MED12 have been reported in an increasing number of males and females with NSID, with affected individuals often having clinical features identified in other MED12-related disorders.
Simpson-Golabi-Behmel syndrome type 1
MedGen UID:
162917
Concept ID:
C0796154
Disease or Syndrome
Simpson-Golabi-Behmel syndrome type 1 (SGBS1) is characterized by pre- and postnatal macrosomia; distinctive craniofacial features (including macrocephaly, coarse facial features, macrostomia, macroglossia, and palatal abnormalities); and commonly, mild-to-severe intellectual disability with or without structural brain anomalies. Other variable findings include supernumerary nipples, diastasis recti / umbilical hernia, congenital heart defects, diaphragmatic hernia, genitourinary defects, and gastrointestinal anomalies. Skeletal anomalies can include vertebral fusion, scoliosis, rib anomalies, and congenital hip dislocation. Hand anomalies can include large hands and postaxial polydactyly. Affected individuals are at increased risk for embryonal tumors including Wilms tumor, hepatoblastoma, adrenal neuroblastoma, gonadoblastoma, hepatocellular carcinoma, and medulloblastoma.
Syndromic X-linked intellectual disability Snyder type
MedGen UID:
162918
Concept ID:
C0796160
Disease or Syndrome
Snyder-Robinson syndrome (SRS) is an X-linked intellectual disability syndrome characterized by asthenic build, facial dysmorphism with a prominent lower lip, kyphoscoliosis, osteoporosis, speech abnormalities, and seizures. Developmental delay usually presents as failure to meet early developmental milestones and then evolves to moderate to profound intellectual disability (which appears to remain stable over time) and variable motor disability. Asthenic habitus and low muscle mass usually develop during the first year, even in males who are ambulatory. During the first decade, males with SRS develop osteoporosis, resulting in fractures in the absence of trauma.
Acromegaloid phenotype with cutis verticis gyrata and corneal leukoma
MedGen UID:
231158
Concept ID:
C1321495
Congenital Abnormality
Congenital generalized lipodystrophy type 1
MedGen UID:
318592
Concept ID:
C1720862
Disease or Syndrome
Berardinelli-Seip congenital lipodystrophy (BSCL) is usually diagnosed at birth or soon thereafter. Because of the absence of functional adipocytes, lipid is stored in other tissues, including muscle and liver. Affected individuals develop insulin resistance and approximately 25%-35% develop diabetes mellitus between ages 15 and 20 years. Hepatomegaly secondary to hepatic steatosis and skeletal muscle hypertrophy occur in all affected individuals. Hypertrophic cardiomyopathy is reported in 20%-25% of affected individuals and is a significant cause of morbidity from cardiac failure and early mortality.
Congenital generalized lipodystrophy type 2
MedGen UID:
318593
Concept ID:
C1720863
Congenital Abnormality
Berardinelli-Seip congenital lipodystrophy (BSCL) is usually diagnosed at birth or soon thereafter. Because of the absence of functional adipocytes, lipid is stored in other tissues, including muscle and liver. Affected individuals develop insulin resistance and approximately 25%-35% develop diabetes mellitus between ages 15 and 20 years. Hepatomegaly secondary to hepatic steatosis and skeletal muscle hypertrophy occur in all affected individuals. Hypertrophic cardiomyopathy is reported in 20%-25% of affected individuals and is a significant cause of morbidity from cardiac failure and early mortality.
Creatine transporter deficiency
MedGen UID:
337451
Concept ID:
C1845862
Disease or Syndrome
The creatine deficiency disorders (CDDs), inborn errors of creatine metabolism and transport, comprise three disorders: the creatine biosynthesis disorders guanidinoacetate methyltransferase (GAMT) deficiency and L-arginine:glycine amidinotransferase (AGAT) deficiency; and creatine transporter (CRTR) deficiency. Developmental delay and cognitive dysfunction or intellectual disability and speech-language disorder are common to all three CDDs. Onset of clinical manifestations of GAMT deficiency (reported in ~130 individuals) is between ages three months and two years; in addition to developmental delays, the majority of individuals have epilepsy and develop a behavior disorder (e.g., hyperactivity, autism, or self-injurious behavior), and about 30% have movement disorder. AGAT deficiency has been reported in 16 individuals; none have had epilepsy or movement disorders. Clinical findings of CRTR deficiency in affected males (reported in ~130 individuals) in addition to developmental delays include epilepsy (variable seizure types and may be intractable) and behavior disorders (e.g., attention deficit and/or hyperactivity, autistic features, impulsivity, social anxiety), hypotonia, and (less commonly) a movement disorder. Poor weight gain with constipation and prolonged QTc on EKG have been reported. While mild-to-moderate intellectual disability is commonly observed up to age four years, the majority of adult males with CRTR deficiency have been reported to have severe intellectual disability. Females heterozygous for CRTR deficiency are typically either asymptomatic or have mild intellectual disability, although a more severe phenotype resembling the male phenotype has been reported.
Phelan-McDermid syndrome
MedGen UID:
339994
Concept ID:
C1853490
Disease or Syndrome
Phelan-McDermid syndrome is characterized by neonatal hypotonia, absent to severely delayed speech, developmental delay, and minor dysmorphic facial features. Most affected individuals have moderate to profound intellectual disability. Other features include large fleshy hands, dysplastic toenails, and decreased perspiration that results in a tendency to overheat. Normal stature and normal head size distinguishes Phelan-McDermid syndrome from other autosomal chromosome disorders. Behavior characteristics include mouthing or chewing non-food items, decreased perception of pain, and autism spectrum disorder or autistic-like affect and behavior.
Hydrocephaly-tall stature-joint laxity syndrome
MedGen UID:
383828
Concept ID:
C1856051
Disease or Syndrome
A multiple congenital anomalies syndrome described in two sisters and with the presence of hydrocephalus (onset in infancy), tall stature, joint laxity, and thoracolumbar kyphosis. There have been no further descriptions in the literature since 1989.
Camptodactyly-tall stature-scoliosis-hearing loss syndrome
MedGen UID:
355844
Concept ID:
C1864852
Disease or Syndrome
This syndrome has characteristics of camptodactyly, tall stature, scoliosis, and hearing loss (CATSHL). It has been described in around 30 individuals from seven generations of the same family. The syndrome is caused by a missense mutation in the FGFR3 gene, leading to a partial loss of function of the encoded protein, which is a negative regulator of bone growth.
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.
46,XX sex reversal 1
MedGen UID:
411324
Concept ID:
C2748895
Disease or Syndrome
Nonsyndromic 46,XX testicular disorders/differences of sex development (DSD) are characterized by: the presence of a 46,XX karyotype; external genitalia ranging from typical male to ambiguous; two testicles; azoospermia; absence of müllerian structures; and absence of other syndromic features, such as congenital anomalies outside of the genitourinary system, learning disorders / cognitive impairment, or behavioral issues. Approximately 85% of individuals with nonsyndromic 46,XX testicular DSD present after puberty with normal pubic hair and normal penile size but small testes, gynecomastia, and sterility resulting from azoospermia. Approximately 15% of individuals with nonsyndromic 46,XX testicular DSD present at birth with ambiguous genitalia. Gender role and gender identity are reported as male. If untreated, males with 46,XX testicular DSD experience the consequences of testosterone deficiency.
46,XY sex reversal 1
MedGen UID:
412662
Concept ID:
C2748896
Disease or Syndrome
Sex reversal in an individual with 46,XY karyotype caused by point mutations or deletions in the SRY gene, encoding sex-determining region Y protein.
Giacheti syndrome
MedGen UID:
414543
Concept ID:
C2752043
Disease or Syndrome
Loeys-Dietz syndrome 4
MedGen UID:
766676
Concept ID:
C3553762
Disease or Syndrome
Loeys-Dietz syndrome (LDS) is characterized by vascular findings (cerebral, thoracic, and abdominal arterial aneurysms and/or dissections), skeletal manifestations (pectus excavatum or pectus carinatum, scoliosis, joint laxity, arachnodactyly, talipes equinovarus, cervical spine malformation and/or instability), craniofacial features (widely spaced eyes, strabismus, bifid uvula / cleft palate, and craniosynostosis that can involve any sutures), and cutaneous findings (velvety and translucent skin, easy bruising, and dystrophic scars). Individuals with LDS are predisposed to widespread and aggressive arterial aneurysms and pregnancy-related complications including uterine rupture and death. Individuals with LDS can show a strong predisposition for allergic/inflammatory disease including asthma, eczema, and reactions to food or environmental allergens. There is also an increased incidence of gastrointestinal inflammation including eosinophilic esophagitis and gastritis or inflammatory bowel disease. Wide variation in the distribution and severity of clinical features can be seen in individuals with LDS, even among affected individuals within a family who have the same pathogenic variant.
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).
Rienhoff syndrome
MedGen UID:
816342
Concept ID:
C3810012
Disease or Syndrome
Loeys-Dietz syndrome (LDS) is characterized by vascular findings (cerebral, thoracic, and abdominal arterial aneurysms and/or dissections), skeletal manifestations (pectus excavatum or pectus carinatum, scoliosis, joint laxity, arachnodactyly, talipes equinovarus, cervical spine malformation and/or instability), craniofacial features (widely spaced eyes, strabismus, bifid uvula / cleft palate, and craniosynostosis that can involve any sutures), and cutaneous findings (velvety and translucent skin, easy bruising, and dystrophic scars). Individuals with LDS are predisposed to widespread and aggressive arterial aneurysms and pregnancy-related complications including uterine rupture and death. Individuals with LDS can show a strong predisposition for allergic/inflammatory disease including asthma, eczema, and reactions to food or environmental allergens. There is also an increased incidence of gastrointestinal inflammation including eosinophilic esophagitis and gastritis or inflammatory bowel disease. Wide variation in the distribution and severity of clinical features can be seen in individuals with LDS, even among affected individuals within a family who have the same pathogenic variant.
X-linked acrogigantism due to Xq26 microduplication
MedGen UID:
856021
Concept ID:
C3891556
Disease or Syndrome
X-linked acrogigantism is the occurrence of pituitary gigantism in an individual heterozygous or hemizygous for a germline or somatic duplication of GPR101. X-linked acrogigantism is characterized by acceleration of linear growth in early childhood – in most cases during the first two years of life – due to growth hormone (GH) excess. Most individuals with X-linked acrogigantism present with associated hyperprolactinemia due to a mixed GH- and prolactin-secreting pituitary adenoma with or without associated hyperplasia; less commonly they develop diffuse hyperplasia of the GH- and prolactin-secreting pituitary cells without a pituitary adenoma. Most affected individuals are females. Growth acceleration is the main presenting feature; other frequently observed clinical features include enlargement of hands and feet, coarsening of the facial features, and increased appetite. Neurologic signs or symptoms are rarely present. Untreated X-linked acrogigantism can lead to markedly increased stature, with obvious severe physical and psychological sequelae.
Tatton-Brown-Rahman overgrowth syndrome
MedGen UID:
862982
Concept ID:
C4014545
Disease or Syndrome
Tatton-Brown-Rahman syndrome (TBRS) is an overgrowth / intellectual disability syndrome characterized by length/height and/or head circumference =2 SD above the mean for age and sex, obesity / increased weight, intellectual disability that ranges from mild to severe, joint hypermobility, hypotonia, behavioral/psychiatric issues, kyphoscoliosis, and seizures. Individuals with TBRS have subtle dysmorphic features, including a round face with coarse features, thick horizontal low-set eyebrows, narrow (as measured vertically) palpebral fissures, and prominent upper central incisors. The facial gestalt is most easily recognizable in the teenage years. TBRS may be associated with an increased risk of developing acute myeloid leukemia. There are less clear associations with aortic root dilatation and increased risk of other hematologic and solid tumors.
Tall stature-scoliosis-macrodactyly of the great toes syndrome
MedGen UID:
863127
Concept ID:
C4014690
Disease or Syndrome
Miura-type epiphyseal chondrodysplasia (ECDM) is an overgrowth syndrome characterized by tall stature, arachnodactyly of the hands, macrodactyly of the great toes, scoliosis, coxa valga, and slipped capital femoral epiphysis (Miura et al., 2014). Multiple extra epiphyses are present in the hands (Boudin et al., 2018). Mutation in the NPR3 gene (108962) results in Boudin-Mortier syndrome (BOMOS; 619543), a similar phenotype of tall stature, arachnodactyly, elongated great toes, and multiple extra epiphyses.
Glucocorticoid deficiency 1
MedGen UID:
885551
Concept ID:
C4049650
Disease or Syndrome
Familial glucocorticoid deficiency is an autosomal recessive disorder resulting from defects in the action of adrenocorticotropic hormone (ACTH) to stimulate glucocorticoid synthesis in the adrenal. Production of mineralocorticoids by the adrenal is normal. Patients present in early life with low or undetectable cortisol and, because of the failure of the negative feedback loop to the pituitary and hypothalamus, grossly elevated ACTH levels (summary by Clark et al., 2009). Genetic Heterogeneity of Familial Glucocorticoid Deficiency Familial glucocorticoid deficiency-2 (GCCD2; 607398) is caused by mutation in the MRAP gene (609196) on chromosome 21q22. GCCD3 (609197) has been mapped to chromosome 8q11.2-q13.2. GCCD4 with or without mineralocorticoid deficiency (614736) is caused by mutation in the NNT gene (607878) on chromosome 5p12. GCCD5 (617825) is caused by mutation in the TXNRD2 gene (606448) on chromosome 22q11.
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).
Myofibrillar myopathy 8
MedGen UID:
934612
Concept ID:
C4310645
Disease or Syndrome
Myofibrillar myopathy-8 (MFM8) is an autosomal recessive myopathy characterized by slowly progressive proximal muscle weakness and atrophy affecting the upper and lower limbs, resulting in increased falls, gait problems, difficulty running or climbing stairs, and upper limb weakness or scapular winging. Some patients develop distal muscle weakness and atrophy. The phenotype may also be consistent with a clinical diagnosis of limb-girdle muscular dystrophy (LGMD). Age at symptom onset ranges from infancy to adulthood. Ambulation is generally preserved and cardiac involvement is rare, but respiratory compromise with decreased forced vital capacity often occurs. Muscle biopsy shows a mix of myopathic features, including myofibrillar inclusions and sarcomeric disorganization; some patients have been reported to have dystrophic changes on muscle biopsy (O'Grady et al., 2016; Daimaguler et al., 2021). There is significant phenotypic variation, even in patients with the same mutation, which must be taken into account when counseling affecting individuals (Woods et al., 2020). For a general phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (601419).
Tall stature-intellectual disability-renal anomalies syndrome
MedGen UID:
934682
Concept ID:
C4310715
Disease or Syndrome
Thauvin-Robinet-Faivre syndrome is an autosomal recessive disorder characterized by generalized overgrowth, mainly of height, and mildly delayed psychomotor development with mild or severe learning difficulties. More variable features may include congenital heart defects, kidney abnormalities, and skeletal defects. Patients may have an increased risk for Wilms tumor (summary by Akawi et al., 2016).
Macrocephaly, dysmorphic facies, and psychomotor retardation
MedGen UID:
934733
Concept ID:
C4310766
Disease or Syndrome
Macrocephaly, dysmorphic facies, and psychomotor retardation (MDFPMR) is an autosomal recessive neurodevelopmental disorder characterized by large head and somatic overgrowth apparent at birth followed by global developmental delay. Affected individuals have characteristic dysmorphic facial features and persistently large head, but increased birth weight normalizes with age. Additional neurologic features, including seizures, hypotonia, and gait ataxia, may also occur. Patients show severe intellectual impairment (summary by Ortega-Recalde et al., 2015).
Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart
MedGen UID:
934739
Concept ID:
C4310772
Disease or Syndrome
RERE-related disorders are characterized by neurodevelopmental problems with or without structural anomalies of the eyes, heart, kidneys, and genitourinary tract and mild sensorineural hearing loss. Hypotonia and feeding problems are common among affected individuals. Developmental delay and intellectual disability range from mild to profound. Behavior problems may include attention-deficit/hyperactivity disorder, self-injurious behavior, and autism spectrum disorder. A variety of eye anomalies (coloboma, optic nerve anomalies, microphthalmia, and/or Peter's anomaly) and vision issues (myopia, anisometropia, astigmatism, exotropia, esotropia) have been reported. Congenital heart defects, most commonly septal defects, have also been described. Genitourinary abnormalities include vesicoureteral reflux, and cryptorchidism and hypospadias in males. Sensorineural hearing loss can be unilateral or bilateral.
Progeroid and marfanoid aspect-lipodystrophy syndrome
MedGen UID:
934763
Concept ID:
C4310796
Disease or Syndrome
The marfanoid-progeroid-lipodystrophy syndrome (MFLS) is characterized by congenital lipodystrophy, premature birth with an accelerated linear growth disproportionate to weight gain, and progeroid appearance with distinct facial features, including proptosis, downslanting palpebral fissures, and retrognathia. Other characteristic features include arachnodactyly, digital hyperextensibility, myopia, dural ectasia, and normal psychomotor development (Takenouchi et al., 2013). Takenouchi et al. (2013) noted phenotypic overlap with Marfan syndrome (154700) and Shprintzen-Goldberg craniosynostosis syndrome (182212).
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).
Cohen-Gibson syndrome
MedGen UID:
1386939
Concept ID:
C4479654
Disease or Syndrome
EED-related overgrowth is characterized by fetal or early childhood overgrowth (tall stature, macrocephaly, large hands and feet, and advanced bone age) and intellectual disability that ranges from mild to severe. To date, EED-related overgrowth has been reported in eight individuals.
Joubert syndrome 32
MedGen UID:
1626697
Concept ID:
C4540342
Disease or Syndrome
Joubert syndrome-32 (JBTS32) is an autosomal recessive developmental disorder characterized by delayed psychomotor development, intellectual disability, dysmorphic facial features, and postaxial polydactyly. Brain imaging shows cerebellar abnormalities consistent with the molar tooth sign (MTS) (summary by De Mori et al., 2017). For discussion of genetic heterogeneity of Joubert syndrome, see JBTS1 (213300).
Ehlers-Danlos syndrome, periodontal type 1
MedGen UID:
1642148
Concept ID:
C4551499
Disease or Syndrome
Periodontal Ehlers-Danlos syndrome (pEDS) is characterized by distinct oral manifestations. Periodontal tissue breakdown beginning in the teens results in premature loss of teeth. Lack of attached gingiva and thin and fragile gums lead to gingival recession. Connective tissue abnormalities of pEDS typically include easy bruising, pretibial plaques, distal joint hypermobility, hoarse voice, and less commonly manifestations such as organ or vessel rupture. Since the first descriptions of pEDS in the 1970s, 148 individuals have been reported in the literature; however, future in-depth descriptions of non-oral manifestations in newly diagnosed individuals with a molecularly confirmed diagnosis of pEDS will be important to further define the clinical features.
Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities
MedGen UID:
1648498
Concept ID:
C4748135
Disease or Syndrome
BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 20
MedGen UID:
1674972
Concept ID:
C4759928
Finding
Obesity due to mutation in the MC4R gene is the most common cause of monogenic obesity. Patients have early-onset severe obesity and hyperphagia (Farooqi et al., 2003).
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).
Imagawa-Matsumoto syndrome
MedGen UID:
1711007
Concept ID:
C5394073
Disease or Syndrome
Imagawa-Matsumoto syndrome (IMMAS) is characterized by variable pre- and postnatal overgrowth; dysmorphic features including postnatal macrocephaly, prominent forehead, round face, hypertelorism, downslanting palpebral fissures, and low and broad nasal bridge; and variable musculoskeletal abnormalities. Developmental delay and impaired intellectual development are common, whereas abnormalities of cerebral imaging are uncommon but may be significant. Some patients exhibit genitourinary abnormalities, and respiratory issues have been reported (Cyrus et al., 2019).
Chromosome 17q11.2 deletion syndrome, 1.4Mb
MedGen UID:
1726802
Concept ID:
C5401456
Disease or Syndrome
Approximately 5 to 20% of all patients with neurofibromatosis type I (162200) carry a heterozygous deletion of approximately 1.4 Mb involving the NF1 gene and contiguous genes lying in its flanking regions (Riva et al., 2000; Jenne et al., 2001), which is caused by nonallelic homologous recombination of NF1 repeats A and C (Dorschner et al., 2000). The 'NF1 microdeletion syndrome' is often characterized by a more severe phenotype than that observed in the majority of NF1 patients. In particular, patients with NF1 microdeletion often show variable facial dysmorphism, mental retardation, developmental delay, an excessive number of early-onset neurofibromas (Venturin et al., 2004), and an increased risk for malignant peripheral nerve sheath tumors (De Raedt et al., 2003).
Vissers-Bodmer syndrome
MedGen UID:
1776566
Concept ID:
C5436647
Disease or Syndrome
Vissers-Bodmer syndrome (VIBOS) is characterized by global developmental delay with variably impaired intellectual development, speech delay, motor delay, and behavioral abnormalities apparent from infancy. The phenotype is highly variable: some individuals have only mild learning difficulties, whereas others have severe cognitive impairment with IQ in the 50s. Many patients have behavioral abnormalities, including autism spectrum disorder, ADD, ADHD, obsessive-compulsive disorder, and impulsivity. Other common features include growth impairment abnormalities, hypotonia, and distal skeletal defects, such as foot and hand deformities. Less common features include seizures, brain abnormalities on MRI, feeding problems, and joint hypermobility. Most individuals have dysmorphic facial features, but there is no recognizable gestalt (summary by Vissers et al., 2020).
Boudin-Mortier syndrome
MedGen UID:
1794202
Concept ID:
C5561992
Disease or Syndrome
Boudin-Mortier syndrome (BOMOS) is characterized by tall stature, arachnodactyly, disproportionately elongated great toes, and multiple extra epiphyses. Some patients also show joint hypermobility and dilation of the aortic root (Boudin et al., 2018). Mutation in the NPR2 gene (108961) results in a similar phenotype of increased stature and elongation of the digits, particularly of the great toes, with multiple extra epiphyses (epiphyseal chondrodysplasia, Miura type; 615923).
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).

Professional guidelines

PubMed

Woelfle J, Schnabel D, Binder G
Dtsch Arztebl Int 2024 Feb 9;121(3):96-106. doi: 10.3238/arztebl.m2023.0247. PMID: 38051162Free PMC Article
Edouard T
Ann Endocrinol (Paris) 2017 Jun;78(2):104-105. Epub 2017 May 4 doi: 10.1016/j.ando.2017.04.007. PMID: 28478947
Hannema SE, Sävendahl L
Horm Res Paediatr 2016;85(5):347-52. Epub 2016 Feb 5 doi: 10.1159/000443685. PMID: 26845047

Recent clinical studies

Etiology

Lui JC, Baron J
J Clin Endocrinol Metab 2024 Jan 18;109(2):312-320. doi: 10.1210/clinem/dgad420. PMID: 37450557
Butler G, Srirangalingam U, Faithfull J, Sangster P, Senniappan S, Mitchell R
Arch Dis Child 2023 Mar;108(3):166-171. Epub 2022 Aug 10 doi: 10.1136/archdischild-2020-320831. PMID: 35948402Free PMC Article
Bardsley MZ, Kowal K, Levy C, Gosek A, Ayari N, Tartaglia N, Lahlou N, Winder B, Grimes S, Ross JL
J Pediatr 2013 Oct;163(4):1085-94. Epub 2013 Jun 27 doi: 10.1016/j.jpeds.2013.05.037. PMID: 23810129Free PMC Article
Tartaglia NR, Howell S, Sutherland A, Wilson R, Wilson L
Orphanet J Rare Dis 2010 May 11;5:8. doi: 10.1186/1750-1172-5-8. PMID: 20459843Free PMC Article
Verge CF, Mowat D
Arch Dis Child 2010 Jun;95(6):458-63. Epub 2010 Apr 6 doi: 10.1136/adc.2009.157693. PMID: 20371592

Diagnosis

Butler G, Srirangalingam U, Faithfull J, Sangster P, Senniappan S, Mitchell R
Arch Dis Child 2023 Mar;108(3):166-171. Epub 2022 Aug 10 doi: 10.1136/archdischild-2020-320831. PMID: 35948402Free PMC Article
Urakami T
Minerva Pediatr 2020 Dec;72(6):472-483. Epub 2020 Aug 4 doi: 10.23736/S0026-4946.20.05971-X. PMID: 32748612
Marques P, Korbonits M
Front Neuroendocrinol 2019 Jan;52:113-143. Epub 2018 Nov 15 doi: 10.1016/j.yfrne.2018.11.001. PMID: 30448536
Tartaglia N, Ayari N, Howell S, D'Epagnier C, Zeitler P
Acta Paediatr 2011 Jun;100(6):851-60. Epub 2011 Apr 8 doi: 10.1111/j.1651-2227.2011.02235.x. PMID: 21342258Free PMC Article
Tartaglia NR, Howell S, Sutherland A, Wilson R, Wilson L
Orphanet J Rare Dis 2010 May 11;5:8. doi: 10.1186/1750-1172-5-8. PMID: 20459843Free PMC Article

Therapy

Woelfle J, Schnabel D, Binder G
Dtsch Arztebl Int 2024 Feb 9;121(3):96-106. doi: 10.3238/arztebl.m2023.0247. PMID: 38051162Free PMC Article
Butler G, Srirangalingam U, Faithfull J, Sangster P, Senniappan S, Mitchell R
Arch Dis Child 2023 Mar;108(3):166-171. Epub 2022 Aug 10 doi: 10.1136/archdischild-2020-320831. PMID: 35948402Free PMC Article
Laron Z
Pediatr Endocrinol Rev 2012 Aug;9(4):696-7. PMID: 23304805
Griffith DE
Curr Opin Infect Dis 2010 Apr;23(2):185-90. doi: 10.1097/QCO.0b013e328336ead6. PMID: 20087178
Lee JM, Howell JD
Arch Pediatr Adolesc Med 2006 Oct;160(10):1035-9. doi: 10.1001/archpedi.160.10.1035. PMID: 17018462

Prognosis

Kayser M, Branicki W, Parson W, Phillips C
Forensic Sci Int Genet 2023 Jul;65:102870. Epub 2023 Apr 6 doi: 10.1016/j.fsigen.2023.102870. PMID: 37084623
Urakami T
Minerva Pediatr 2020 Dec;72(6):472-483. Epub 2020 Aug 4 doi: 10.23736/S0026-4946.20.05971-X. PMID: 32748612
Meazza C, Gertosio C, Giacchero R, Pagani S, Bozzola M
Ital J Pediatr 2017 Aug 3;43(1):66. doi: 10.1186/s13052-017-0385-5. PMID: 28774346Free PMC Article
Hannema SE, Sävendahl L
Horm Res Paediatr 2016;85(5):347-52. Epub 2016 Feb 5 doi: 10.1159/000443685. PMID: 26845047
Tartaglia NR, Howell S, Sutherland A, Wilson R, Wilson L
Orphanet J Rare Dis 2010 May 11;5:8. doi: 10.1186/1750-1172-5-8. PMID: 20459843Free PMC Article

Clinical prediction guides

Kayser M, Branicki W, Parson W, Phillips C
Forensic Sci Int Genet 2023 Jul;65:102870. Epub 2023 Apr 6 doi: 10.1016/j.fsigen.2023.102870. PMID: 37084623
Urakami T
Minerva Pediatr 2020 Dec;72(6):472-483. Epub 2020 Aug 4 doi: 10.23736/S0026-4946.20.05971-X. PMID: 32748612
Meazza C, Gertosio C, Giacchero R, Pagani S, Bozzola M
Ital J Pediatr 2017 Aug 3;43(1):66. doi: 10.1186/s13052-017-0385-5. PMID: 28774346Free PMC Article
Edouard T
Ann Endocrinol (Paris) 2017 Jun;78(2):104-105. Epub 2017 May 4 doi: 10.1016/j.ando.2017.04.007. PMID: 28478947
Hannema SE, Sävendahl L
Horm Res Paediatr 2016;85(5):347-52. Epub 2016 Feb 5 doi: 10.1159/000443685. PMID: 26845047

Recent systematic reviews

Shrestha RM, Mizoue T, Sawada N, Matsuo K, Wada K, Tanaka K, Lin Y, Sugawara Y, Takimoto H, Kimura T, Ito H, Kitamura T, Sakata R, Tanaka S, Inoue M; Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan
Jpn J Clin Oncol 2022 Apr 6;52(4):322-330. doi: 10.1093/jjco/hyab203. PMID: 34969070
Flannigan R, Patel P, Paduch DA
Sex Med Rev 2018 Oct;6(4):595-606. Epub 2018 Apr 19 doi: 10.1016/j.sxmr.2018.02.008. PMID: 29680294
Han Z, Lutsiv O, Mulla S, McDonald SD; Knowledge Synthesis Group
J Obstet Gynaecol Can 2012 Aug;34(8):721-746. doi: 10.1016/S1701-2163(16)35337-3. PMID: 22947405

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