Williams Syndrome Clinical Presentation
- Author: Joanna Lazier, MD; Chief Editor: Howard S Weber, MD, FSCAI more...
The history obtained from caregivers of patients with Williams syndrome varies and reflects the wide phenotypic spectrum observed in the syndrome. This includes a pattern of growth and development and a specific neurodevelopmental profile primarily involving 4 areas: cognitive development, language, auditory function, and visuospatial function, as in the following[46, 47, 48] :
- Children have prenatal and postnatal growth delay and usually present with failure to thrive. Short stature is common in children who are shorter than their family background, and adults reach a mean height that is often below the third percentile. A history of feeding problems and poor weight gain is common.
- A history of recurrent middle ear infections and/or effusions in childhood and progressive mild-to-moderate high frequency sensorineural hearing loss is noted in most adolescents and adults.
- A history of visual disturbances is possible. These are mainly related to esotropia, cataracts, and hyperopia in as many as 50% of individuals with Williams syndrome.
- A history of congenital heart disease is common, and hypertension may be noted.
- In children, functional problems, including a history of increased urinary frequency and daytime wetting, is possible. Delayed toilet training is not uncommon. A history of renal abnormalities is also possible, as well as a history of hypercalcemia and hypercalciuria.
- A history of connective tissue abnormalities, such as abnormal joint mobility, hernias, and diverticula, is possible.
- Children may have histories of chronic abdominal pain, and they are at increased risk for celiac disease.
- Children with Williams syndrome typically have mild-to-moderate mental retardation, but the range includes severe mental retardation to average intelligence. Abilities should be considered on an individual basis due to the wide variability among individuals. Impaired motor development is often apparent before age 42 months.
- Early language acquisition is delayed,[56, 57] and although mild-to-moderate language impairments persist throughout life, the quality and affect of speech are relatively normal.
- Visual-spatial problems impact daily life, with difficulties in handwriting, drawing, and gait apraxia, especially on uneven or sandy surfaces.
- Interest and enthusiasm for music is almost universal in patients with Williams syndrome, but the ability to perform professionally is exceptional.
- As many as half of all children with Williams syndrome may exhibit autism spectrum social and communicative deficits.
- Children with Williams syndrome are described as overly friendly, hyperactive, inattentive, and hypersensitive to loud sounds or certain types of sounds.[60, 61]
Phenotypic expression of Williams syndrome widely varies. Virtually all cases have typical facial features that can be recognized even at birth, as in the following:
- Children with Williams syndrome are generally full-term infants with prenatal growth delay. Specific growth curves for Williams syndrome have been established.
- Microcephaly is observed in one third of children, and postnatal failure to thrive is typical.
- Virtually all children and adults with Williams syndrome have some combination of the following facial features: short upturned nose, flat nasal bridge, long philtrum, flat malar area, wide mouth, full lips, dental malocclusion and widely spaced teeth, micrognathia, and periorbital fullness. A stellate, lacy pattern of the irises can be observed in children with blue eyes. The voice may be hoarse. Nails tend to be hypoplastic and the skin soft and lax, and the halluces have a valgus deviation.
- Problems with primary and secondary dentition include small and peg-shaped teeth, increased interdental spacing, absence of one or more primary or secondary teeth, anterior cross-bite malocclusion, and excessive gingival tissue.[69, 70, 71]
- The diagnosis of Williams syndrome should also be considered after an incidental finding of idiopathic hypercalcemia or a characteristic cardiac lesion such as supravalvar aortic stenosis (SVAS). Other cardiac lesions in patients with Williams syndrome can include pulmonary stenosis and mitral valve regurgitation.[44, 64] Arterial hypertension may be present. If the distinct facial features are not evident, consider referral to a practitioner experienced in examining the facial features of Williams syndrome, such as a clinical geneticist or cardiologist experienced in dysmorphology.
- Ocular findings can include strabismus (usually due to esotropia), a stellate iris, cataract, retinal vascular tortuosity, and reduced binocular vision; a case of Reiger anomaly has even been reported.[43, 72, 73]
- Sensorineural hearing loss can be present and is likely underdiagnosed. It is often progressive in nature, and it can be aggravated by conductive loss due to middle ear effusions.
- Examine patients for signs of precocious puberty.
- Other findings include hyperacusis (despite hearing loss), hoarse voice, joint hyperelasticity, contractures, kyphoscoliosis, and lordosis.
- Monitor for hypertension at every visit.
- Generalized hypotonia is found in infants with Williams syndrome and progresses to spasticity with age.
- Dental issues can include microdontia, enamel hypoplasia, and malocclusion.
A deletion on band 7q11.23 near the elastin gene is identified in virtually all individuals with Williams syndrome. The underlying etiology is believed to be unequal meiotic crossover events that lead to interstitial deletions.[75, 76] These deletions may result in unbalanced interchromosomal and, to a lesser extent, intrachromosomal rearrangements.
Mechanisms whereby chromosomes paired during meiosis may undergo unequal crossover resulting in Williams syndrome have typically been thought to result from an unequal overlap of repetitive Alu sequences flanking the region, resulting in a type of misalignment of the chromosomal regions during a crossover event.
In addition, another mechanism that has recently been shown includes a familial inversion polymorphism in the Williams syndrome region that may predispose to unequal crossover during meiosis.
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