Genotype-phenotype correlation in two sets of monozygotic twins with Williams syndrome

Abstract

We report on two sets of monozygotic (MZ) twins with Williams syndrome (WS), following the 6 pairs already reported in the literature. We have confirmed monozygosity of both pairs of twins by DNA microsatellite analysis and the clinical diagnosis by fluorescence in situ hybridization using a WS-specific probe. Analysis of the concordance of different clinical signs between members of each pair of twins benefitted from a lengthy clinical follow-up, from 24 months to 7 years in one pair, and from the age of 15 years with reevaluation after 2 years in the other pair. Most clinical signs were concordant in the twins of each pair, with differences present at younger ages, mainly minor facial anomalies, being attenuated with time. Developmental delay was substantially concordant, but the degree differed slightly between twins in each pair. Inguinal hernia was present in a single twin in pair 1. Facial anomalies and other signs attributable to connective tissue abnormalities were also displayed by only one twin in both sets, suggesting that the WS genotype has only a predisposing role in the development of these signs.

The genomic basis of the Williams – Beuren syndrome

“…Studies on monozygotic twins suffering from WBS revealed that most clinical signs, i.e. cardiac defects and abnormal behavioural features are concordant, whereas birth weight, stature and grade of mental retardation seem to be influenced also by environmental factors [21]. Adults with WBS suffer predominantly from the consequences of cardiac defects and hypertension, sensorineural hearing loss, subclinical hypothyroidism, gastrointestinal problems and urinary tract abnormalities.…”

Twins with Williams-Beuren Syndrome and Discordance for Wilms Tumor

“…All are characteristic for WBS, but genotypephenotype correlation is complicated by variable penetrance and other genetic and epigenetic differences in twins. [3,4] Twin A was diagnosed with WT at the age of 4.5 years, presenting with acute abdominal pain and vomiting. CT scan revealed a 6.5 × 8 cm 2 tumor originating from left kidney and numerous lesions in the liver.…”

“…Twin B had an inguinal hernia at birth. All are characteristic for WBS, but genotype–phenotype correlation is complicated by variable penetrance and other genetic and epigenetic differences in twins …”

Familial Williams-Beuren syndrome

“…In addition to the findings already described, hypoplasia of the right kidney and thickening of the mitral valve were found at the autopsy. [Morris et al, 1988]; concordant monozygotic twins have been reported [Castorina et al, 1997Murphy et al, 1990Pankau et al, 1993]. A few cases of parentto-child transmission of WBS have been published so far.…”