Clinical and Genetic Aspects of Phelan-McDermid Syndrome: An Interdisciplinary Approach to Management

Genes (Basel). 2022 Mar 12;13(3):504. doi: 10.3390/genes13030504.


Phelan-McDermid syndrome (PMS) is a rare, heterogeneous, and complex neurodevelopmental disorder. It is generally caused by a heterozygous microdeletion of contiguous genes located in the distal portion of the long arm of chromosome 22, including the SHANK3 gene. Sequence variants of SHANK3, including frameshift, nonsense mutations, small indels and splice site mutations also result in PMS. Furthermore, haploinsufficiency in SHANK3 has been suggested as the main cause of PMS. SHANK3 is also associated with intellectual disability, autism spectrum disorder and schizophrenia. The phenotype of PMS is variable, and lacks a distinctive phenotypic characteristic, so the clinical diagnosis should be confirmed by genetic analysis. PMS is a multi-system disorder, and clinical care must encompass various specialties and therapists. The role of risperidone, intranasal insulin, insulin growth factor 1, and oxytocin as potential therapeutic options in PMS will be discussed in this review. The diagnosis of PMS is important to provide an appropriate clinical evaluation, treatment, and genetic counseling.

Keywords: Phelan–McDermid syndrome; SHANK3; etiology; evaluation; treatment.

Publication types

  • Review

MeSH terms

  • Autism Spectrum Disorder* / genetics
  • Chromosome Deletion
  • Chromosome Disorders* / diagnosis
  • Chromosome Disorders* / genetics
  • Chromosome Disorders* / therapy
  • Chromosomes, Human, Pair 22 / genetics
  • Humans
  • Insulin / genetics


  • Insulin

Supplementary concepts

  • Telomeric 22q13 Monosomy Syndrome