Evaluation of clinical and genetic findings in patients with Williams syndrome

Introduction: Williams Syndrome was first described in 1961 by cardiologist J.C.P. Williams and his colleagues, who identified it in a patient with supravalvular aortic stenosis, intellectual disability, and characteristic facial features. One year later, A.J. Beuren described patients with similar features, and the syndrome became known as "Williams-Beuren syndrome" . Williams Syndrome is a rare neurodevelopmental disorder with an estimated prevalence of 1 in 20,000 individuals. The diagnosis is confirmed through genomic testing that detects a deletion at the 7q11.23 chromosomal region, which includes the elastin gene.The diagnosis of Williams Syndrome is based on a comprehensive evaluation of typical facial features, developmental delay, short stature, connective tissue abnormalities, and characteristic cognitive and behavioral features. In most affected individuals, this deletion occurs sporadically. Advances in genetic testing techniques have increased early diagnosis rates, and multidisciplinary treatment approaches have improved the quality of life for patients. This study aims to determine the demographic, phenotypic, systemic, clinical, biochemical, radiological, cytogenetic and molecular genetic findings of patients diagnosed with Williams Syndrome and to evaluate accompanying genetic anomalies. Materials and Methods: This study is a retrospective study conducted at Ankara Bilkent City Hospital, Pediatric Genetics Department of the Children's Hospital. It includes data from 45 patients diagnosed with Williams syndrome who were admitted and followed between March 1, 2018, and December 31, 2023. The patients history, physical examination findings, laboratory values, and imaging results were obtained retrospectively from the hospital based electronic record system. Results: A total of 45 patients under the age of 18 who were diagnosed with Williams Syndrome based on clinical and molecular findings were included in this study. Of these patients, 24 (53.3%) were female and 21 (46.7%) were male, with a mean age at diagnosis of 2.5 years. Cardiovascular system pathologies were detected in 86.7% of the patients, urogenital anomalies in 37.8%, musculoskeletal system pathologies in 42.2%, renal anomalies in 37.5%, endocrine disorders in 42.2%, gastrointestinal system issues in 40%, ocular pathologies in 32.5%, and neurological anomalies in 17.8%. Diagnosis was established in 81% of the patients using fluorescence in situ hybridization analysis and in 26.2% using microarray analysis. One of our patients died during follow-up. Conclusion: Although the diagnosis of Williams Syndrome is primarily based on clinical criteria, genetic testing serves as an essential complement due to the age-dependent variability of disease symptoms. Genetic diagnosis confirms the diagnosis of Williams Syndrome, facilitates monitoring the disease course and potential complications, and is particularly helpful in diagnosing atypical cases. Determining genotype-phenotype correlations allows for better prediction of disease progression. Patients diagnosed with Williams Syndrome may encounter various problems at different stages of life; therefore, adequate information should be provided to them and their families. Supportive therapies play a key role in improving patients' quality of life. Keywords: Williams Syndrome, 7q11.23 deletion, Williams Beuren Syndrome