Abstract

THE GENETIC TRAJECTORIES OF WILLIAMS–BEUREN SYNDROME: A DELETION AT 7q11.23

Dr. Alisha Naaz, Dr. Afsha Anjum, Shifa Aashmeen, Stuti Gupta and *Rajat Kumar

ABSTRACT

Williams syndrome (WS), also called Williams-Beuren syndrome, is a rare genetic disorder (1:7,500-1:20,000 births) caused by a 7q11.23 chromosomal deletion involving approximately 26-28 genes, including the critical ELN gene responsible for elastin production. First described independently by Williams (1961) and Beuren (1962), this multisystem condition presents with distinctive facial features (broad forehead, periorbital fullness, stellate iris pattern, short nose, and full cheeks), cardiovascular abnormalities (notably supravalvular aortic stenosis in 75% of cases), endocrine dysfunction (hypercalcemia, growth hormone deficiency), connective tissue abnormalities, and characteristic neurodevelopmental features including mild-to-moderate intellectual disability with relative preservation of language skills, severe visuospatial deficits, and a unique hypersocial personality. Diagnosis combines recognition of this clinical phenotype with genetic confirmation via FISH or microarray analysis. Management requires coordinated multidisciplinary care involving cardiologists (for monitoring and surgical intervention when needed), endocrinologists (for calcium and growth management), developmental specialists (providing speech, occupational, and physical therapies), and mental health professionals. While most cases occur sporadically, affected individuals have a 50% chance of transmitting the condition to offspring. Prognosis largely depends on cardiovascular involvement, with current approaches enabling many patients to achieve semi-independent living and near-normal life expectancy, though they remain at lifelong risk for  cardiovascular complications, the leading cause of mortality. Ongoing research continues to refine our understanding of genotype-phenotype correlations and optimize therapeutic strategies for this complex disorder.

Keywords: Williams syndrome, Neurodevelopmental disorder, Chromosomes, Elfin-like, FISH, Microarray analysis.