Adaptive behavior in Chinese children with Williams syndrome.

BACKGROUND: Williams syndrome (WS) is a neurodevelopmental disease characterized by compelling psychological phenotypes. The symptoms span multiple cognitive domains and include a distinctive pattern of social behavior. The goal of this study was to explore adaptive behavior in WS patients in China. METHODS: We conducted a structured interview including the Infants-Junior Middle School Students Social-life Abilities Scale in three participant groups: children with WS (n = 26), normally-developing children matched for mental age (MA, n = 30), and normally-developing children matched for chronological age (CA, n = 40). We compared the mean scores for each domain between the three groups. RESULTS: Children with WS had more siblings than children in the two control groups. The educational level of the caregivers of WS children was lower than that of the control children. We found no differences in locomotion, work skill, socialization, or self-management between the WS and MA groups. WS children obtained higher scores of self-dependence (df = 54, Z = -2.379, p = 0.017) and had better communication skills (df = 54, Z = -2.222, p = 0.026) compared with MA children. The CA children achieved higher scores than the WS children for all dimensions of adaptive behavior. CONCLUSIONS: WS children have better adaptive behavior skills regarding communication and self-dependence than normal children matched for mental age. Targeted intervention techniques should be designed to promote social development in this population.

Nature and nurture: Williams syndrome across cultures.

This study is concerned with ways in which children with Williams syndrome (WS), a rare neurodevelopmental disorder arising from a hemizygous deletion in chromosome band 7q11.23 including the gene for elastin (ELN) and approximately 20 surrounding genes, are affected by social mores of vastly differing cultures: the United States and Japan. WS presents a compelling model for the investigation because its genetic phenotype is well defined and results in an uneven cognitive profile as well as a social phenotype typical of the syndrome including overt over-friendliness toward strangers. While a number of research groups have been studying the cognitive strengths and weaknesses of individuals with WS in various countries, there have not been studies to date that explore the social phenotype in WS across different cultures. This study examines the ways in which social behavior in WS, stemming from specific genetic underpinnings, might be mediated by cultural expectations. We conducted a cross-cultural study using an instrument that measures aspects of sociability commonly found among people with WS. Quantitative analyses revealed a significant effect of diagnostic category in that in both countries, children with WS were rated as significantly higher in global sociability and more likely to approach strangers than were their normal counterparts. There was also an effect of culture, in that regardless of category, WS and normal children in Japan were rated lower than their counterparts in the US. We suggest that the excessively social phenotype of children with Williams syndrome, although markedly present across cultures, appears to vary in its intensity by culture. This is an intriguing illustration of interactions between nature and nurture.

Outcome of pulmonary and aortic stenosis in Williams-Beuren syndrome in an Asian cohort.

AIMS: To define the cardiovascular anomalies and the long-term outcomes in an Asian cohort with Williams-Beuren syndrome (WBS). METHODS: Data were retrieved from a retrospective chart review of patients who had a definitive diagnosis of WBS by fluorescence in situ hybridization between 1995 and 2005. All patients underwent echocardiography every 3-9 months. Ten patients underwent cardiac catheterization. RESULTS: Twenty-one patients with a total follow-up of 134 patient-years (median: 72 months) were enrolled. Characteristic dysmorphic facial features were noted in 19 patients (n = 19, 90%). All except one had associated cardiac anomalies, accounting for 0.3% (20/6640) of the patients with congenital heart disease. The spectrum of cardiac anomalies included supravalvular aortic stenosis (SVAS) (n = 15, 71%), peripheral pulmonary stenosis (PPS) (n = 12, 57%), pulmonary valve stenosis (PS) (n = 10, 47%), mitral valve prolapse (MVP) (n = 9, 43%), coarcation of the aorta (n = 4, 19%), ventricular septal defect (n = 2, 10%) and atrial septal defect (n = 1, 5%). Concurrent SVAS and PS/PPS were found in 14 (70%) patients. Only one patient required balloon dilation of PS, which improved. Regression of the stenoses occurred with a probability of 31, 90 and 71% at the age of 10 years for SAVS, PS and PPS, respectively. CONCLUSIONS: Among our WBS patients, SVAS, PPS and PS were common, and were associated with probability of spontaneous regression, especially of right-sided lesions.

Delineation of the common critical region in Williams syndrome and clinical correlation of growth, heart defects, ethnicity, and parental origin.

Williams syndrome (WS) is a neurodevelopmental disorder with a variable phenotype. Molecular genetic studies have indicated that hemizygosity at the elastin locus (ELN) may account for the cardiac abnormalities seen in WS, but that mental retardation and hypercalcemia are likely caused by other genes flanking ELN. In this study, we defined the minimal critical deletion region in 63 patients using 10 microsatellite markers and 5 fluorescence in situ hybridization (FISH) probes on chromosome 7q, flanking ELN. The haplotype analyses showed the deleted cases to have deletions of consistent size, as did the FISH analyses using genomic probes for the known ends of the commonly deleted region defined by the satellite markers. In all informative cases deleted at ELN, the deletion extends from D7S489U to D7S1870. The genetic distance between these two markers is about 2 cM. Of the 51 informative patients with deletions, 29 were maternal and 22 were paternal in origin. There was no evidence for effects on stature by examining gender, ethnicity, cardiac status, or parental origin of the deletion. Heteroduplex analysis for LIMK1, a candidate gene previously implicated in the WS phenotype, did not show any mutations in our WS patients not deleted for ELN. LIMK1 deletions were found in all elastin-deletion cases who had WS. One case, who has isolated, supravalvular aortic stenosis and an elastin deletion, was not deleted for LIMK1. It remains to be determined if haploinsufficiency of LIMK1 is responsible in part for the WS phenotype or is simply deleted due to its close proximity to the elastin locus.