The WBS phenotype is quite variable, as would be expected for a developmental disorder, but there are a number of core clinical features that are present in the vast majority of affected individuals. These include both physical and neurological elements that combine to produce a unique and therefore characteristic clinical picture. The frequency of WBS has been estimated at between 1 in 20,000 and 1 in 7500, with the second statistic likely a more accurate reflection of the population frequency because it was generated from a larger data set (9,10).
Physical manifestations of WBS usually include involvement of the cardiovascular system, most often as a narrowing of the ascending aorta (SVAS) although a generalized arteriopathy can lead to vascular stenoses in other vessels, and hypertension is common in later life. Stellate irides, flat nasal bridge, short, up-turned nose with anteverted nostrils, long philtrum, full lips and lower cheeks, and a small chin are the recognizable facial features. Other symptoms include hernias, visual impairment, hypersensitivity to sound, chronic otitis media, malocclusion, small or missing teeth, renal anomalies, constipation, vomiting, growth deficiency, infantile hypercalcemia, musculoskeletal abnormalities, and a hoarse voice (11,12). As WBS individuals grow older they may also present with premature graying of the hair, diabetes and impaired glucose tolerance, decreased bone mineral density, sensorineural hearing loss, and a high frequency of psychiatric symptoms (13).
Individuals with WBS usually have mild mental retardation, with an average intelligence quotient (IQ) of between 55 and 60, although there is a wide range of recorded values. The most striking aspect of the WBS phenotype is the distinct behavioral profile, which encompasses a unique combination of both friendliness and anxiety (11,14). It is characterized by impaired cognition, hyperreactivity, sensory integration dysfunction, delayed expressive and receptive language skills, and multiple developmental motor disabilities affecting balance, strength, coordination, and motor planning (12). In addition, approx 70% of WBS individuals suffer from attention deficit and hyperactivity disorder and there is a high incidence of anxiety and simple phobias (12,15,16).
WBS was linked to chromosome 7q11.23 through the occurrence of a part of the phenotypic spectrum, SVAS, as an independent autosomal dominant disorder. SVAS was mapped to 7q11.23 through linkage analysis (17) and the elastin gene (ELN) was then found to be disrupted in an individual with a t(6;7) chromosome translocation (2). The vast majority of individuals presenting with the classic symptoms of WBS harbor a deletion of 7q11.23 (18-21). Individuals without rearrangements of 7q11.23, or with rearrangements of other regions of the genome have been reported, but these are likely misdiagnoses or perhaps phenocopies of WBS (22-28).
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