Williams syndrome: an update on clinical and molecular aspects
- Department of Clinical Genetics
- St Mary’s Hospital
- Manchester M13 0JH, UK
Williams syndrome is a neurodevelopmental disorder associated with a characteristic physical and behavioural phenotype. The syndrome was described in 1961 by Williams et al who recognised a group of children with supravalvar aortic stenosis, mental retardation, and dysmorphic facial features.1 Beurenet al independently described the syndrome, noting also the friendly nature of these children, and later expanded it to include dental anomalies and peripheral pulmonary artery stenosis.2 3 Subsequent authors recognised the association with idiopathic hypercalcaemia.
Williams syndrome is caused by a microdeletion on chromosome 7 and the diagnosis can be confirmed by FISH studies
Ongoing medical surveillance should include monitoring of blood pressure and renal function
Williams syndrome is proving an interesting model for studying the molecular basis of cognition and behaviour
Since the discovery in 19934 that Williams syndrome is caused by a chromosomal microdeletion, features resulting from the deletion of contiguous genes, there has been increasing interest in trying to unravel the underlying molecular basis of the cognitive and behavioural aspects of this syndrome.
Infants with Williams syndrome are usually born following an uneventful pregnancy with an average birth weight of 2760 g. In the neonatal period feeding problems are common and often accompanied by vomiting and poor weight gain. Frequent crying, sleeping problems, and constipation are also frequently reported by parents, and rectal prolapse occurs in around 10% of cases. Hernias, most commonly inguinal, occur in over a third of cases. A proportion of infants are found to have idiopathic hypercalcaemia, which is treated with a low calcium and vitamin D restricted diet. The underlying hormonal basis for the hypercalcaemia is not known, although there is a delayed calcitonin response to a calcium load on testing. Resolution of hypercalcaemia occurs spontaneously, usually at around 18–24 months of age.
Developmental milestones …