From the Guidelines
Williams syndrome is a multisystem genetic disorder caused by a deletion of part of chromosome 7, characterized by dysmorphic facies, cardiovascular disease, intellectual disability, and a characteristic cognitive profile. According to the American Academy of Pediatrics 1, Williams syndrome is present at birth with a prevalence of 1 in 7500 and affects boys and girls equally. The deleted portion of chromosome 7q11.23 contains 26 to 28 genes, including the ELN gene that codes for the structural protein elastin, which is an important component of the elastic fibers found in the connective tissue of many organs. Some key characteristics of Williams syndrome include:
- Dysmorphic facies (100%)
- Cardiovascular disease (80%; most commonly supravalvular aortic stenosis [SVAS])
- Intellectual disability (75%)
- A characteristic cognitive profile (90%)
- Idiopathic hypercalcemia (15% to 45%) The pathogenesis of other characteristics, such as intellectual disability, is likely attributable to deletion of contiguous genes in the region 1. Affected individuals have a 50% chance of transmitting the deletion to offspring. Management of Williams syndrome focuses on managing specific symptoms through cardiac care, developmental therapies, educational support, and sometimes medications for associated conditions like anxiety or attention problems, with early intervention being crucial for maximizing development 1.
From the Research
Definition and Prevalence of Williams Syndrome
- Williams syndrome is a genetic disorder caused by a deletion involving chromosome 7, resulting in various clinically significant abnormalities 2, 3.
- It is a relatively rare microdeletion disorder, occurring in as many as 1 in 7,500 individuals 3 or 1 in 10,000 live births 2.
- The deletion size is similar across most individuals with Williams syndrome and leads to the loss of one copy of 25-27 genes on chromosome 7q11.23 3.
Characteristics and Features of Williams Syndrome
- The disorder affects multiple systems, with cardinal features including:
- Cardiovascular disease, characteristically stenosis of the great arteries and most notably supravalvar aortic stenosis 3.
- A distinctive craniofacial appearance, often described as "elfin" 2.
- A specific cognitive and behavioural profile, including intellectual disability and hypersociability 3.
- Hypercalcemia, which can be recurrent and is observed in both children and adults with Williams syndrome 2, 4.
Genetic Basis and Phenotypic Variability
- The genotype-phenotype evidence is strongest for the genes ELN, GTF2I, and GTF2IRD1, which are responsible for the vascular and connective tissue features, intellectual ability, social functioning, and anxiety in Williams syndrome 3.
- Other genes, such as BAZ1B, LIMK1, STX1A, and MLXIPL, may also contribute to the clinical outcomes, but more research is needed to understand their mechanisms 3.
- Phenotypic variability is considerable for all cardinal features of Williams syndrome, but the specific sources of this variability remain unknown 3.