Clinical Characterization of Phelan-Mcdermid Syndrome

Phelan-McDermid syndrome or 22q13.3 deletion syndrome is a neurodevelopmental disorder caused by deletion of chromosome 22q13.3 or pathogenic variant in SHANK3 gene. Phelan-McDermid syndrome is characterized by global developmental delay, intellectual disability, autism spectrum disorder, hypotonia, seizures, severely delayed or absentspeech, and minor facial anomalies. To date, about 1300 individuals with Phelan-McDermid syndrome are reported worldwide according to Phelan-McDermid Syndrome Foundation. It is believed that the prevalence is considerably greater. This condition has long been under-diagnosed due to difficulty in detecting microdeletions by available methods, therefore, the preva­lence is unknown. Recent microarray techniques enabled to identify previously undetectable microdeletions responsible for the syndrome. We report a 12 year old girl presenting with severe intellectual disability, stereotypic hand movements, disturbed sleep, episodes of hyperactivity, unsteady gait, teeth grinding, hyperpnoe, and delayed puberty. Genetic tests showed no evidence of chromosomal anomaly, monogenic disease or inherited metabolic dis­order. Whole exome sequencing revealed a pathogenic variant in SHANK3 gene, confirming diagnosis of Phelan-McDermid syndrome. Genetic testing and determination of molecular diagnosis influences patient’s treatment, management and prevention of comorbid diseases. Finally, family is given information about prognosis, recurrence risk and possibility for prenatal diagnosis.