Phelan-McDermid syndrome: genotype-phenotype correlation and identification of an atypical case

chromosome 22


Phelan-McDermid Syndrome (PMS), also known as 22q13 Deletion Syndrome, is a rare genetic disorder caused by deletions in the 22q13.3 region involving the SHANK3 gene, Sometimes mutations in the SHANK3 gene may produce the same condition. Clinical features in patients broadly vary and include global developmental delay, intellectual disability (ID), autism spectrum disorder (ASD), and mild dysmorphisms. The authors explored the genotype-phenotype correlation in a cohort of 34 PMS individuals and also described an individual with a mild phenotype.

The authors found that 21% of PMS individuals in the study had additional copy number variations (CNVs), which could contribute to the variable phenotype in PMS. The most common clinical features found in the study cohort were abnormal pain tolerance and hypotonia. Additional clinical features included sparse eyebrows, difficulty chewing, and ASD. Renal abnormalities and lymphedema were found to be significantly correlated with the deletion size.

Additionally, the authors found one atypical individual. He had the smallest deletion size (0.11 Mb). Only a part of the SHANK3 gene was deleted in this patient. Surprisingly he had normal IQ, although revealed some behavioral abnormalities. This finding expands the PMS phenotype and suggests that some individuals can show some resiliency to the deficiency of SHANK3 function.

Samogy-Costa CI, Varella-Branco B, Monfardini F, et al. “A Brazilian Cohort of Individuals with Phelan-McDermid Syndrome: Genotype-Phenotype Correlation and Identification of an Atypical Case.” Journal of Neurodevelopmental Disorders 2019, v. 11:13.

Articles of the month are chosen from newly published genetic research by CDO geneticist, Dr. Iosif Lurie.  For more information on any article please contact info@chromodisorder.org


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