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Williams-Beuren syndrome (WS) is a rare multi-system genomic disorder, caused by 7q11.23 microdeletion with a prevalence of 1/7500-1/20,000 live births. Clinical phenotype includes typical facial dysmorphism (elfin face), mental retardation associated with a peculiar neuropsychological profile and congenital heart defects. We investigated 22 WS patients (mean age of 9.7 years, range 1 day to 39 years) with a multi-specialist follow-up protocol comprehensive of neuropsychological, cardiologic, nephrologic, ophthalmologic, endocrinologic, gastroenterologic, odontostomatologic and orthopaedic evaluations. The mean age at diagnosis was 5.38 years, being 1.02 years when genetic evaluation was requested for congenital heart defects (CHD) and 10.68 years in case of mental retardation and/or abnormal neuropsychological profile without an evident CHD. All patients showed facial dysmorphisms, with supravalvular aortic stenosis (SVAS) as the most common cardiovascular anomaly (12/22), followed by peripheral pulmonary stenosis (9/22); interestingly, in one patient we detected a total anomalous pulmonary venous return (TAPVR), confirming the possible association of this rare CHD with WS. Hypertension was detected by 24-h ambulatory blood pressure monitoring in 7/22 cases. A cognitive assessment was performed in 13 patients older than 6 years, showing various degrees of mental retardation in 12 and a normal intelligence quotient (IQ) in a single patient; evaluation of developmental milestones revealed various grades of developmental delay in all the patients younger than 6 years. Chiari malformation type 1 was found in 3 patients. Our study underlines a remarkable diagnostic delay in patients who present to genetic evaluation because of mental retardation and/or peculiar neuropsychological profile lacking an evident cardiopathy and confirms the multi-systemic nature of WS leading to a high clinical presentation's variability and complex follow-up strategies.

Purpose: We evaluated the experiences of 19 Italian laboratories concerning 241 small supernumerary marker chromosomes (sSMCs) with the aim of answering questions arising from their origin from any chromosome, their variable size and genetic content, and their impact on the carrier's phenotype., Methods: Conventional protocols were used to set up the cultures and chromosome preparations. Both commercial and homemade probes were used for the fluorescent in situ hybridization analyses., Results: A total of 113 of the 241 sSMCs were detected antenatally, and 128 were detected postnatally. There were 52 inherited and 172 de novo cases. Abnormal phenotype was present in 137 cases (57%), 38 of which were antenatally diagnosed. A mosaic condition was observed in 87 cases (36%). In terms of morphology, monocentric and dicentric bisatellited marker chromosomes were the most common, followed by monocentric rings and short-arm isochromosomes. The chromosomes generating the sSMCs were acrocentric in 132 cases (69%) and non-acrocentric chromosomes in 60 cases (31%); a neocentromere was hypothesized in three cases involving chromosomes 6, 8, and 15., Conclusion: The presented and published data still do not allow any definite conclusions to be drawn concerning karyotype-phenotype correlations. Only concerted efforts to characterize molecularly the sSMCs associated or not with a clinical phenotype can yield results suitable for addressing karyotype-phenotype correlations in support of genetic counseling.