Williams syndrome is characterized by multiple system abnormalities consistent with it being a contiguous gene deletion syndrome. It has been demonstrated that the majority of Williams syndrome patients are hemizygous for de novo deletions at 7q11.23. There is variability in the deletion size which is probably related to the variable phenotypic presentation of Williams syndrome patients. In the majority of cases (>90%), the hemizygous deletion includes the elastin locus (ELN) .
In the past, FISH studies have been used to identify the hemizygous deletion in query Williams syndrome patients. These studies clearly demonstrate the presence of a deletion in the majority of cases but do not reveal the parental origin of the deletion. Although there appears to be no bias with regard to the parental origin of the deletion, recent studies have suggested that the parental origin of the deletion plays a significant role in the clinical prognosis of the proband (AJHG 59:781-792). The data presented in this paper indicate that Williams syndrome patients with a deletion of maternal origin have significantly more severe growth retardation and microcephaly. The apparent Williams syndrome critical region and some of the markers used by the lab to determine deletion status and deletion parent-of-origin are shown in the figure below.