Presenting phenotype and clinical evaluation in a cohort of 22 Williams-Beuren syndrome patients

Abstract

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.