- Williams-Beuren syndrome (WBS), a.k.a. Williams syndrome, is a multisystem neurodevelopmental disorder characterized by subtle, distinctive facial features and intellectual disabilities, including a characteristic cognitive behavioral profile.
- Growth retardation, hoarse voice, connective tissue abnormalities, vascular stenoses (supravalvular aortic, peripheral pulmonary, renal artery), high blood pressure (BP), endocrine abnormalities (hypercalcemia; diabetes; subclinical and, less often, clinical hypothyroidism), early puberty, musculoskeletal abnormalities (limited joint movement, lordosis), bowel and bladder diverticula
- System(s) affected: cardiovascular, GI, endocrine, musculoskeletal, CNS, renal/urologic
- Synonym(s): Williams syndrome; Fanconi-type idiopathic infantile hypercalcemia; elfin facies with hypercalcemia
- ~1/7,500 live births
- Predominant sex: male = female
Etiology and Pathophysiology
- Microdeletion of WBS critical region (WBSCR) produced by unequal crossing over chromosome 7 in meiosis due to blocks of low copy repeats
- The deleted interval contains the ELN gene, encoding the elastin protein, an important component of elastic fibers in the connective tissue, particularly medium- and large-sized arteries. 50% of the dry weight of the normal aorta is elastin.
- Some features of WBS have no obvious relationship to elastin but are caused by loss of other genes in the WBSCR.
- WBS is a contiguous gene deletion (microdeletion) disorder involving 26 to 28 genes on chromosome 7q11.23, likely leading to underexpression of products of genes in the WBSCR.
- Online Mendelian Inheritance in Man #194050
- Phenotypic expression is variable.
- Nearly always sporadic (de novo deletion in chromosome 7)
- Individuals with WBS have a 50% chance of transmitting WBS to each of their offspring.
- Inversion of the WBSCR is a benign polymorphism; however, carriers are slightly more likely to produce a gamete with a deleted WBSCR.
Commonly Associated Conditions
- Cardiovascular (1)
- Supravalvular aortic stenosis (SVAS) (trivial to severe) in 70%; may be present at birth but often develops or progresses during childhood (rare except in WBS), LVH (40%)
- Pulmonary arterial stenosis (40%), tends to ameliorate with age
- Middle aortic syndrome in which thoracic and abdominal aorta and branches are narrowed
- Renal artery stenosis (60%)
- Hypertension (HTN) (50%) often without surgically repairable renovascular lesions
- Prolonged QTc interval (14%)
- Cardiovascular mortality 25 to 100 times that of general population
- Endocrine (1)
- Calcium: 5–50% have ≥1 hypercalcemic episode.
- Diabetes: high prevalence of prediabetes or overt diabetes (>60% of adults), especially with high BMI
- Thyroid: subclinical hypothyroidism (15–30%), often with mild thyroid hypoplasia. Overt hypothyroidism occurs as well but less often.
- Puberty: Average age at menarche is 10 years; early puberty is the norm.
- Early adolescent growth spurt in majority, contributing to diminished adult stature
Pediatric multivitamins (which all contain vitamin D) should be used with caution; may precipitate infantile hypercalcemia
- Neurodevelopmental (1)
- Development and cognition
- Delayed early motor skills and achievement of language milestones
- Strong social and interpersonal skills
- Average IQ 50 to 60 (mild to moderate disability), range 40 to 100
- Some verbal abilities are relatively spared. Individuals have better performance on verbal tasks than on visual tasks.
- Dramatic weakness in visuospatial and visuomotor skills
- Frequent and significant impairment of attention (attention deficit disorder [ADD] or attention deficit hyperactivity disorder [ADHD]), resulting in distractibility
- Personality, behavioral, and emotional
- Most patients are friendly and empathetic.
- The overly social “cocktail party” personality is well-described but not fully accurate.
- Behavioral and psychiatric difficulties are common: 50–90% of adolescents and adults meet DSM-IV criteria for anxiety disorder, phobic disorder, and/or ADHD.
- Enjoyment of music is common; sensitivity to noise is noted in up to 90%.
- Development and cognition
- GI (1): Colic, difficulty feeding, and intolerance to food textures are common during infancy; at other ages: chronic constipation, gastroesophageal reflux, diverticular disease, abdominal pain of unknown etiology, rectal prolapse, (rarely) celiac disease
- Genitourinary (1): delayed toilet training, voiding frequency, urgency, enuresis, structural renal abnormalities, bladder diverticula, and more rarely, nephrocalcinosis
There's more to see -- the rest of this topic is available only to subscribers.
Domino, Frank J., et al., editors. "Williams-Beuren Syndrome." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2020. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688597/all/Williams_Beuren_Syndrome.
Williams-Beuren Syndrome. In: Domino FJF, Baldor RAR, Golding JJ, et al, eds. 5-Minute Clinical Consult. Wolters Kluwer; 2020. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688597/all/Williams_Beuren_Syndrome. Accessed May 29, 2023.
Williams-Beuren Syndrome. (2020). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (27th ed.). Wolters Kluwer. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688597/all/Williams_Beuren_Syndrome
Williams-Beuren Syndrome [Internet]. In: Domino FJF, Baldor RAR, Golding JJ, Stephens MBM, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2020. [cited 2023 May 29]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688597/all/Williams_Beuren_Syndrome.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Williams-Beuren Syndrome ID - 1688597 ED - Domino,Frank J, ED - Baldor,Robert A, ED - Golding,Jeremy, ED - Stephens,Mark B, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688597/all/Williams_Beuren_Syndrome PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -