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Williams syndrome(WBS)

MedGen UID:
59799
Concept ID:
C0175702
Disease or Syndrome
Synonyms: CHROMOSOME 7q11.23 DELETION SYNDROME, 1.5- TO 1.8-MB; WBS; Williams-Beuren syndrome
SNOMED CT: Williams syndrome (63247009); William syndrome (63247009); Williams Beuren syndrome (63247009); Deletion 7q11.23 (63247009); Monosomy 7q11.23 (63247009)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Genes (locations): ELN (7q11.23); MLXIPL (7q11.23)
 
Monarch Initiative: MONDO:0008678
OMIM®: 194050
Orphanet: ORPHA904

Disease characteristics

Excerpted from the GeneReview: Williams Syndrome
Williams syndrome (WS) is characterized by developmental delay, intellectual disability (usually mild), a specific cognitive profile, unique personality characteristics, cardiovascular disease (supravalvar aortic stenosis, peripheral pulmonary stenosis, hypertension), connective tissue abnormalities, growth deficiency, endocrine abnormalities (early puberty, hypercalcemia, hypercalciuria, hypothyroidism), and distinctive facies. Hypotonia and hyperextensible joints can result in delayed attainment of motor milestones. Feeding difficulties often lead to poor weight gain in infancy. [from GeneReviews]
Authors:
Colleen A Morris   view full author information

Additional descriptions

From OMIM
Williams-Beuren syndrome is a multisystem disorder caused by hemizygous deletion of 1.5 to 1.8 Mb on chromosome 7q11.23, which contains approximately 28 genes. Pober (2010) reviewed the clinical features of Williams-Beuren syndrome as well as the genomic and genetic basis and clinical management. See also the distal chromosome 7q11.23 deletion syndrome (613729), which occurs between the WBS region and the MAGI2 gene (606382).  http://www.omim.org/entry/194050
From MedlinePlus Genetics
Williams syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by mild to moderate intellectual disability or learning problems, unique personality characteristics, distinctive facial features, and heart and blood vessel (cardiovascular) problems.

People with Williams syndrome typically have difficulty with visual-spatial tasks such as drawing and assembling puzzles, but they tend to do well on tasks that involve spoken language, music, and learning by repetition (rote memorization). Affected individuals have outgoing, engaging personalities and tend to take an extreme interest in other people. Attention deficit disorder (ADD), problems with anxiety, and phobias are common among people with this disorder.

Young children with Williams syndrome have distinctive facial features including a broad forehead, puffiness around the eyes, a flat bridge of the nose, full cheeks, and a small chin. Many affected people have dental problems such as teeth that are small, widely spaced, crooked, or missing. Older children and adults typically have a longer face with a wide mouth and full lips. 

A form of cardiovascular disease called supravalvular aortic stenosis (SVAS) occurs frequently in people with Williams syndrome. Supravalvular aortic stenosis is a narrowing of the large blood vessel that carries blood from the heart to the rest of the body (the aorta). If this condition is not treated, the aortic narrowing can lead to shortness of breath, chest pain, and heart failure. Narrowing of other vessels, including the artery from the heart to the lungs (pulmonary stenosis) and the arteries that supply blood to the heart (coronary artery stenosis) can also occur. Other problems with the heart and blood vessels, including high blood pressure (hypertension) and stiff blood vessels, have also been reported in people with Williams syndrome. Individuals with Williams syndrome have an increased risk of complications with the use of anesthesia.

Additional signs and symptoms of Williams syndrome include abnormalities of connective tissue (tissue that supports the body's joints and organs) such as joint problems and soft, loose skin. Affected people may also have increased calcium levels in the blood (hypercalcemia) in infancy, developmental delays, problems with coordination, and short stature. Medical problems involving vision or hearing, including sensitivity to sound (hyperacusis), are frequently associated with Williams syndrome. In addition, problems with the digestive tract and the urinary system are also possible. Obesity or diabetes can develop in adulthood.  https://medlineplus.gov/genetics/condition/williams-syndrome

Clinical features

From HPO
Sudden death
MedGen UID:
8257
Concept ID:
C0011071
Pathologic Function
Rapid and unexpected death.
Enuresis
MedGen UID:
8649
Concept ID:
C0014394
Disease or Syndrome
Lack of the ability to control the urinary bladder leading to involuntary urination at an age where control of the bladder should already be possible.
Hypercalciuria
MedGen UID:
43775
Concept ID:
C0020438
Finding
Abnormally high level of calcium in the urine.
Nephrocalcinosis
MedGen UID:
10222
Concept ID:
C0027709
Disease or Syndrome
Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.
Urethral stenosis
MedGen UID:
12016
Concept ID:
C0041974
Finding
Abnormal narrowing of the urethra.
Vesicoureteral reflux
MedGen UID:
21852
Concept ID:
C0042580
Disease or Syndrome
Vesicoureteral reflux (VUR) is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys. It is a risk factor for urinary tract infections. Primary VUR results from a developmental defect of the ureterovesical junction (UVJ). In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy (RN). Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, and renal insufficiency (summary by Lu et al., 2007). Genetic Heterogeneity of Vesicoureteral Reflux A locus designated VUR1 maps to chromosome 1p13. VUR2 (610878) is caused by mutation in the ROBO2 gene (602431) on chromosome 3p12; VUR3 (613674) is caused by mutation in the SOX17 gene (610928) on chromosome 8q11; VUR4 (614317) maps to chromosome 5; VUR5 (614318) maps to chromosome 13; VUR6 (614319) maps to chromosome 18; VUR7 (615390) maps to chromosome 12; and VUR8 (615963) is caused by mutation in the TNXB gene (600985) on chromosome 6p21. A possible X-linked form has been reported (VURX; 314550).
Diverticulum of bladder
MedGen UID:
57625
Concept ID:
C0156273
Finding
Diverticulum (sac or pouch) in the wall of the urinary bladder.
Pelvic kidney
MedGen UID:
67446
Concept ID:
C0221209
Congenital Abnormality
A developmental defect in which a kidney is located in an abnormal anatomic position within the pelvis.
Recurrent urinary tract infections
MedGen UID:
120466
Concept ID:
C0262655
Disease or Syndrome
Repeated infections of the urinary tract.
Renal hypoplasia
MedGen UID:
120571
Concept ID:
C0266295
Congenital Abnormality
Hypoplasia of the kidney.
Renal insufficiency
MedGen UID:
332529
Concept ID:
C1565489
Disease or Syndrome
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.
Micropenis
MedGen UID:
1633603
Concept ID:
C4551492
Congenital Abnormality
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
Abnormal renal morphology
MedGen UID:
1633142
Concept ID:
C4551596
Anatomical Abnormality
Any structural anomaly of the kidney.
Hallux valgus
MedGen UID:
5416
Concept ID:
C0018536
Anatomical Abnormality
Lateral deviation of the great toe (i.e., in the direction of the little toe).
Clinodactyly of the 5th finger
MedGen UID:
340456
Concept ID:
C1850049
Congenital Abnormality
Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).
Supravalvar aortic stenosis
MedGen UID:
2001
Concept ID:
C0003499
Disease or Syndrome
Supravalvular aortic stenosis (SVAS) is a heart defect that develops before birth. This defect is a narrowing (stenosis) of the large blood vessel that carries blood from the heart to the rest of the body (the aorta). The condition is described as supravalvular because the section of the aorta that is narrowed is located just above the valve that connects the aorta with the heart (the aortic valve). Some people with SVAS also have defects in other blood vessels, most commonly stenosis of the artery from the heart to the lungs (the pulmonary artery). An abnormal heart sound during a heartbeat (heart murmur) can often be heard during a chest exam. If SVAS is not treated, the aortic narrowing can lead to shortness of breath, chest pain, and ultimately heart failure.\n\nThe severity of SVAS varies considerably, even among family members. Some affected individuals die in infancy, while others never experience symptoms of the disorder.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Portal hypertension
MedGen UID:
9375
Concept ID:
C0020541
Disease or Syndrome
Increased pressure in the portal vein.
Mitral regurgitation
MedGen UID:
7670
Concept ID:
C0026266
Disease or Syndrome
An abnormality of the mitral valve characterized by insufficiency or incompetence of the mitral valve resulting in retrograde leaking of blood through the mitral valve upon ventricular contraction.
Mitral valve prolapse
MedGen UID:
7671
Concept ID:
C0026267
Disease or Syndrome
One or both of the leaflets (cusps) of the mitral valve bulges back into the left atrium upon contraction of the left ventricle.
Renal artery stenosis
MedGen UID:
19727
Concept ID:
C0035067
Disease or Syndrome
The presence of stenosis of the renal artery.
Stroke disorder
MedGen UID:
52522
Concept ID:
C0038454
Disease or Syndrome
Sudden impairment of blood flow to a part of the brain due to occlusion or rupture of an artery to the brain.
Bicuspid aortic valve
MedGen UID:
57436
Concept ID:
C0149630
Congenital Abnormality
Aortic valve disease-2 (AOVD2) is characterized by bicuspid aortic valve (BAV) and dilation of the ascending aorta. Calcification of the valve and the aorta has been observed, and some patients exhibit coarctation of the aorta (Tan et al., 2012; Luyckx et al., 2019; Park et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of aortic valve disease, see AOVD1 (109730).
Coronary artery stenosis
MedGen UID:
66859
Concept ID:
C0242231
Disease or Syndrome
Abnormal narrowing of the coronary artery.
Myxomatous mitral valve degeneration
MedGen UID:
488811
Concept ID:
C0264885
Disease or Syndrome
Myxomatous mitral valve is defined as the presence of excess leaflet tissue and leaflet thickening greater than 5 mm, resulting in a prolapse greater than 2 mm into the left atrium on parasternal long axis view.
Peripheral pulmonary artery stenosis
MedGen UID:
138014
Concept ID:
C0345030
Finding
Stenosis of a peripheral branch of the pulmonary artery.
Pulmonic stenosis
MedGen UID:
408291
Concept ID:
C1956257
Disease or Syndrome
A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis).
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Obesity
MedGen UID:
18127
Concept ID:
C0028754
Disease or Syndrome
Accumulation of substantial excess body fat.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Failure to thrive in infancy
MedGen UID:
358083
Concept ID:
C1867873
Finding
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
Colonic diverticula
MedGen UID:
3878
Concept ID:
C0012819
Disease or Syndrome
The presence of multiple diverticula of the colon.
Rectal prolapse
MedGen UID:
11151
Concept ID:
C0034888
Disease or Syndrome
Protrusion of the rectal mucous membrane through the anus.
Chronic constipation
MedGen UID:
98325
Concept ID:
C0401149
Sign or Symptom
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.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Gastroesophageal reflux
MedGen UID:
1368658
Concept ID:
C4317146
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Large earlobe
MedGen UID:
334979
Concept ID:
C1844573
Finding
Increased volume of the earlobe, that is, abnormally prominent ear lobules.
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
Hyperacusis
MedGen UID:
20497
Concept ID:
C0034880
Sign or Symptom
Over-sensitivity to certain frequency ranges of sound.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Atypical behavior
MedGen UID:
535345
Concept ID:
C0233514
Mental or Behavioral Dysfunction
Atypical behavior is an abnormality in a person's actions, which can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.
Short attention span
MedGen UID:
82652
Concept ID:
C0262630
Finding
Reduced attention span characterized by distractibility and impulsivity.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Incoordination
MedGen UID:
141714
Concept ID:
C0520966
Finding
Poor coordination
MedGen UID:
107874
Concept ID:
C0563243
Finding
Chiari type I malformation
MedGen UID:
196689
Concept ID:
C0750929
Congenital Abnormality
Arnold-Chiari type I malformation refers to a relatively mild degree of herniation of the posteroinferior region of the cerebellum (the cerebellar tonsils) into the cervical canal with little or no displacement of the fourth ventricle. It is characterized by one or both pointed (not rounded) cerebellar tonsils that project 5 mm below the foramen magnum, measured by a line drawn from the basion to the opisthion (McRae Line)
Phonophobia
MedGen UID:
155864
Concept ID:
C0751466
Mental or Behavioral Dysfunction
An abnormally heightened sensitivity to loud sounds.
Attention deficit hyperactivity disorder
MedGen UID:
220387
Concept ID:
C1263846
Mental or Behavioral Dysfunction
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.
Obsessive-compulsive trait
MedGen UID:
322417
Concept ID:
C1834433
Finding
The presence of one or more obsessive-compulsive personality traits. Obsessions refer to persistent intrusive thoughts, and compulsions to intrusive behaviors, which the affected person experiences as involuntary, senseless, or repugnant.
Gait imbalance
MedGen UID:
373028
Concept ID:
C1836150
Finding
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Impaired visuospatial constructive cognition
MedGen UID:
869275
Concept ID:
C4023701
Finding
Reduced ability affecting mainly visuospatial cognition which may be tested using pattern construction (for example by Differential Ability Scales, which test a person's strengths and weaknesses across a range of intellectual abilities).
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Radioulnar synostosis
MedGen UID:
57861
Concept ID:
C0158761
Congenital Abnormality
An abnormal osseous union (fusion) between the radius and the ulna.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Kyphoscoliosis
MedGen UID:
154361
Concept ID:
C0575158
Anatomical Abnormality
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Down-sloping shoulders
MedGen UID:
346461
Concept ID:
C1856872
Finding
Low set, steeply sloping shoulders.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Pectus excavatum
MedGen UID:
781174
Concept ID:
C2051831
Finding
A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance.
Celiac disease
MedGen UID:
3291
Concept ID:
C0007570
Disease or Syndrome
Celiac disease is a systemic autoimmune disease that can be associated with gastrointestinal findings (diarrhea, malabsorption, abdominal pain and distension, bloating, vomiting, and weight loss) and/or highly variable non-gastrointestinal findings (dermatitis herpetiformis, chronic fatigue, joint pain/inflammation, iron deficiency anemia, migraines, depression, attention-deficit disorder, epilepsy, osteoporosis/osteopenia, infertility and/or recurrent fetal loss, vitamin deficiencies, short stature, failure to thrive, delayed puberty, dental enamel defects, and autoimmune disorders). Classic celiac disease, characterized by mild to severe gastrointestinal symptoms, is less common than non-classic celiac disease, characterized by absence of gastrointestinal symptoms.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Hypercalcemia
MedGen UID:
5686
Concept ID:
C0020437
Disease or Syndrome
An abnormally increased calcium concentration in the blood.
Food intolerance
MedGen UID:
57440
Concept ID:
C0149696
Finding
A detrimental reaction to a food, beverage, food additive, or compound found in foods that produces symptoms in one or more body organs and systems that is not mediated by an immune reaction.
Glucose intolerance
MedGen UID:
75760
Concept ID:
C0271650
Disease or Syndrome
Glucose intolerance (GI) can be defined as dysglycemia that comprises both prediabetes and diabetes. It includes the conditions of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and diabetes mellitus (DM).
Hoarse voice
MedGen UID:
5602
Concept ID:
C0019825
Sign or Symptom
Hoarseness refers to a change in the pitch or quality of the voice, with the voice sounding weak, very breathy, scratchy, or husky.
Vocal cord paralysis
MedGen UID:
53047
Concept ID:
C0042928
Disease or Syndrome
A loss of the ability to move the vocal folds.
Blepharophimosis
MedGen UID:
2670
Concept ID:
C0005744
Congenital Abnormality
A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.
Partial congenital absence of teeth
MedGen UID:
43794
Concept ID:
C0020608
Congenital Abnormality
Tooth agenesis in some form is a common human anomaly that affects approximately 20% of the population. Although tooth agenesis is associated with numerous syndromes, several case reports describe nonsyndromic forms that are either sporadic or familial in nature, as reviewed by Gorlin et al. (1990). The incidence of familial tooth agenesis varies with each class of teeth. Most commonly affected are third molars (wisdom teeth), followed by either upper lateral incisors or lower second premolars; agenesis involving first and second molars is very rare. Also see 114600 and 302400. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). Faulty use of the terms, however, have confounded their use. The term 'partial anodontia' is obsolete (Salinas, 1978). Genetic Heterogeneity of Selective Tooth Agenesis Other forms of selective tooth agenesis include STHAG2 (602639), mapped to chromosome 16q12; STHAG3 (604625), caused by mutation in the PAX9 gene (167416) on chromosome 14q12; STHAG4 (150400), caused by mutation in the WNT10A gene (606268) on chromosome 2q35; STHAG5 (610926), mapped to chromosome 10q11; STHAG7 (616724), caused by mutation in the LRP6 gene (603507) on chromosome 12p13; STHAG8 (617073), caused by mutation in the WNT10B gene (601906) on chromosome 12q13; STHAG9 (617275), caused by mutation in the GREM2 gene (608832) on chromosome 1q43; STHAG10 (620173), caused by mutation in the TSPEAR gene (612920) on chromosome 21q22; and STHAGX1 (313500), caused by mutation in the EDA gene (300451) on chromosome Xq13. A type of selective tooth agenesis that was formerly designated STHAG6 has been incorporated into the dental anomalies and short stature syndrome (DASS; 601216). Of 34 unrelated patients with nonsyndromic tooth agenesis, van den Boogaard et al. (2012) found that 56% (19 patients) had mutations in the WNT10A gene (STHAG4), whereas only 3% and 9% had mutations in the MSX1 (STHAG1) and PAX9 (STHAG3) genes, respectively. The authors concluded that WNT10A is a major gene in the etiology of isolated hypodontia. Genotype-Phenotype Correlations Yu et al. (2016) observed that the most frequently missing permanent teeth in WNT10B-associated oligodontia were the lateral incisors (83.3%), whereas premolars were missing only 51.4% of the time, which they noted was a pattern 'clearly different' from the oligodontia patterns resulting from WNT10A mutations. They also stated that the selective pattern in WNT10B mutants was different from that associated with mutations in other genes, such as MSX1, in which second premolars are missing, and PAX9, in which there is agenesis of molars.
Dental malocclusion
MedGen UID:
9869
Concept ID:
C0024636
Anatomical Abnormality
Dental malocclusion refers to an abnormality of the occlusion, or alignment, of the teeth and the way the upper and lower teeth fit together, resulting in overcrowding of teeth or in abnormal bite patterns.
Microdontia
MedGen UID:
66008
Concept ID:
C0240340
Congenital Abnormality
Decreased size of the teeth, which can be defined as a mesiodistal tooth diameter (width) more than 2 SD below mean. Alternatively, an apparently decreased maximum width of tooth.
Open mouth
MedGen UID:
116104
Concept ID:
C0240379
Finding
A facial appearance characterized by a permanently or nearly permanently opened mouth.
Broad nasal tip
MedGen UID:
98424
Concept ID:
C0426429
Finding
Increase in width of the nasal tip.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Thick lower lip vermilion
MedGen UID:
326567
Concept ID:
C1839739
Finding
Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective).
Narrow forehead
MedGen UID:
326956
Concept ID:
C1839758
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective).
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Medial flaring of the eyebrow
MedGen UID:
336722
Concept ID:
C1844562
Finding
An abnormal distribution of eyebrow hair growth in the medial direction.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Full cheeks
MedGen UID:
355661
Concept ID:
C1866231
Finding
Increased prominence or roundness of soft tissues between zygomata and mandible.
Periorbital fullness
MedGen UID:
1710990
Concept ID:
C4760994
Finding
Increase in periorbital soft tissue.
Cutis laxa
MedGen UID:
8206
Concept ID:
C0010495
Disease or Syndrome
Wrinkled, redundant, inelastic and sagging skin.
Premature graying of hair
MedGen UID:
75524
Concept ID:
C0263498
Finding
Development of gray hair at a younger than normal age.
Small nail
MedGen UID:
537942
Concept ID:
C0263523
Finding
A nail that is diminished in length and width, i.e., underdeveloped nail.
Soft skin
MedGen UID:
336730
Concept ID:
C1844592
Finding
Subjective impression of increased softness upon palpation of the skin.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.
Early onset of sexual maturation
MedGen UID:
868001
Concept ID:
C4022392
Finding
An early onset of puberty, in this case early does not refer to precocious.
Amblyopia
MedGen UID:
8009
Concept ID:
C0002418
Disease or Syndrome
Reduced visual acuity that is uncorrectable by lenses in the absence of detectable anatomic defects in the eye or visual pathways.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Hypotelorism
MedGen UID:
96107
Concept ID:
C0424711
Finding
Interpupillary distance less than 2 SD below the mean (alternatively, the appearance of an decreased interpupillary distance or closely spaced eyes).
Blue irides
MedGen UID:
108297
Concept ID:
C0578626
Finding
A markedly blue coloration of the iris.
Abnormality of refraction
MedGen UID:
871349
Concept ID:
C4025843
Anatomical Abnormality
An abnormality in the process of focusing of light by the eye in order to produce a sharp image on the retina.
Retinal arteriolar tortuosity
MedGen UID:
1830276
Concept ID:
C5779554
Finding
The presence of an increased number of twists and turns of the retinal arterioles.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVWilliams syndrome
Follow this link to review classifications for Williams syndrome in Orphanet.

Professional guidelines

PubMed

Morris CA, Braddock SR; COUNCIL ON GENETICS
Pediatrics 2020 Feb;145(2) Epub 2020 Jan 21 doi: 10.1542/peds.2019-3761. PMID: 31964759
Collins Ii RT, Collins MG, Schmitz ML, Hamrick JT
Congenit Heart Dis 2017 Mar;12(2):133-142. doi: 10.1111/chd.12447. PMID: 28382779
Blackmer AB, Feinstein JA
Pharmacotherapy 2016 Jan;36(1):84-98. doi: 10.1002/phar.1686. PMID: 26799351

Recent clinical studies

Etiology

Nassisi M, Mainetti C, Aretti A, Sperti A, Nicotra V, Rinaldi B, Natacci F, Bedeschi MF, Viola F
Curr Opin Ophthalmol 2023 Nov 1;34(6):514-521. Epub 2023 Aug 17 doi: 10.1097/ICU.0000000000000990. PMID: 37589562
Deitch AM, Giacone HM, Chubb H, Algaze CA, Lechich KM, Collins RT
Am J Cardiol 2023 May 15;195:91-97. Epub 2023 Apr 8 doi: 10.1016/j.amjcard.2023.03.004. PMID: 37037070
Thom RP, Pober BR, McDougle CJ
Expert Opin Drug Saf 2021 Mar;20(3):293-306. Epub 2021 Jan 11 doi: 10.1080/14740338.2021.1867535. PMID: 33369485
Staudt GE, Eagle SS
J Cardiothorac Vasc Anesth 2021 Jan;35(1):176-186. Epub 2020 Jan 21 doi: 10.1053/j.jvca.2020.01.022. PMID: 32127269
Collins RT 2nd
Curr Opin Pediatr 2018 Oct;30(5):609-615. doi: 10.1097/MOP.0000000000000664. PMID: 30045083

Diagnosis

Saponaro F
Endocrinol Metab Clin North Am 2021 Dec;50(4):769-779. doi: 10.1016/j.ecl.2021.07.004. PMID: 34774247
Kozel BA, Barak B, Kim CA, Mervis CB, Osborne LR, Porter M, Pober BR
Nat Rev Dis Primers 2021 Jun 17;7(1):42. doi: 10.1038/s41572-021-00276-z. PMID: 34140529Free PMC Article
Nat Rev Dis Primers 2021 Jun 17;7(1):43. doi: 10.1038/s41572-021-00283-0. PMID: 34140526
Morris CA, Braddock SR; COUNCIL ON GENETICS
Pediatrics 2020 Feb;145(2) Epub 2020 Jan 21 doi: 10.1542/peds.2019-3761. PMID: 31964759
Pober BR
N Engl J Med 2010 Jan 21;362(3):239-52. doi: 10.1056/NEJMra0903074. PMID: 20089974

Therapy

Thom RP, Pober BR, McDougle CJ
Expert Opin Drug Saf 2021 Mar;20(3):293-306. Epub 2021 Jan 11 doi: 10.1080/14740338.2021.1867535. PMID: 33369485
Staudt GE, Eagle SS
J Cardiothorac Vasc Anesth 2021 Jan;35(1):176-186. Epub 2020 Jan 21 doi: 10.1053/j.jvca.2020.01.022. PMID: 32127269
Glasson EJ, Buckley N, Chen W, Leonard H, Epstein A, Skoss R, Jacoby P, Blackmore AM, Bourke J, Downs J
J Am Acad Child Adolesc Psychiatry 2020 Sep;59(9):1036-1048. Epub 2020 Jan 13 doi: 10.1016/j.jaac.2020.01.006. PMID: 31945412
Collins Ii RT, Collins MG, Schmitz ML, Hamrick JT
Congenit Heart Dis 2017 Mar;12(2):133-142. doi: 10.1111/chd.12447. PMID: 28382779
Blackmer AB, Feinstein JA
Pharmacotherapy 2016 Jan;36(1):84-98. doi: 10.1002/phar.1686. PMID: 26799351

Prognosis

Deitch AM, Giacone HM, Chubb H, Algaze CA, Lechich KM, Collins RT
Am J Cardiol 2023 May 15;195:91-97. Epub 2023 Apr 8 doi: 10.1016/j.amjcard.2023.03.004. PMID: 37037070
Çalışkan E, Şahin MN, Güldağ MA
Yale J Biol Med 2021 Dec;94(4):623-635. Epub 2021 Dec 29 PMID: 34970101Free PMC Article
Crespi BJ, Procyshyn TL
Neurosci Biobehav Rev 2017 Aug;79:14-26. Epub 2017 May 10 doi: 10.1016/j.neubiorev.2017.05.004. PMID: 28499504
Radlović N
Srp Arh Celok Lek 2013 Jan-Feb;141(1-2):122-6. doi: 10.2298/sarh1302122r. PMID: 23539923
Toga AW, Thompson PM, Sowell ER
Trends Neurosci 2006 Mar;29(3):148-59. Epub 2006 Feb 10 doi: 10.1016/j.tins.2006.01.007. PMID: 16472876Free PMC Article

Clinical prediction guides

Deitch AM, Giacone HM, Chubb H, Algaze CA, Lechich KM, Collins RT
Am J Cardiol 2023 May 15;195:91-97. Epub 2023 Apr 8 doi: 10.1016/j.amjcard.2023.03.004. PMID: 37037070
Okazaki S, Kimura R, Otsuka I, Tomiwa K, Funabiki Y, Hagiwara M, Murai T, Hishimoto A
J Child Psychol Psychiatry 2022 Dec;63(12):1553-1562. Epub 2022 Apr 13 doi: 10.1111/jcpp.13613. PMID: 35416284
Farran EK, Hudson KD, Bennett A, Ameen A, Misheva I, Bechlem B, Blades M, Courbois Y
Dev Neuropsychol 2022 Apr-Jun;47(3):136-157. Epub 2022 Mar 14 doi: 10.1080/87565641.2022.2047685. PMID: 35282728
Çalışkan E, Şahin MN, Güldağ MA
Yale J Biol Med 2021 Dec;94(4):623-635. Epub 2021 Dec 29 PMID: 34970101Free PMC Article
Crespi BJ, Procyshyn TL
Neurosci Biobehav Rev 2017 Aug;79:14-26. Epub 2017 May 10 doi: 10.1016/j.neubiorev.2017.05.004. PMID: 28499504

Recent systematic reviews

Serrano-Juárez CA, Prieto-Corona B, Rodríguez-Camacho M, Sandoval-Lira L, Villalva-Sánchez ÁF, Yáñez-Téllez MG, López MFR
Neuropsychol Rev 2023 Dec;33(4):891-911. Epub 2022 Dec 15 doi: 10.1007/s11065-022-09571-2. PMID: 36520254
Çalışkan E, Şahin MN, Güldağ MA
Yale J Biol Med 2021 Dec;94(4):623-635. Epub 2021 Dec 29 PMID: 34970101Free PMC Article
Van Herwegen J, Simms V
Res Dev Disabil 2020 May;100:103609. Epub 2020 Feb 19 doi: 10.1016/j.ridd.2020.103609. PMID: 32087508
Glasson EJ, Buckley N, Chen W, Leonard H, Epstein A, Skoss R, Jacoby P, Blackmore AM, Bourke J, Downs J
J Am Acad Child Adolesc Psychiatry 2020 Sep;59(9):1036-1048. Epub 2020 Jan 13 doi: 10.1016/j.jaac.2020.01.006. PMID: 31945412
Silva LAF, Kim CA, Matas CG
Codas 2018 Sep 17;30(5):e20170267. doi: 10.1590/2317-1782/20182017267. PMID: 30231111

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