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

Francisco Cammarata Scalisi, Michele Callea, Diego Martinelli, Colin Eric Willoughby, Antonio Cárdenas Tadich, Maykol Araya Castillo, María Angelina Lacruz-Rengel, Marco Medina, Piercesare Grimaldi, Enrico Bertini, Julián Nevado

Research output: Contribution to journalReview articlepeer-review

7 Citations (Scopus)
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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.

Original languageEnglish
Article number504
Pages (from-to)1-12
Number of pages12
Issue number3
Early online date12 Mar 2022
Publication statusPublished (in print/issue) - 12 Mar 2022

Bibliographical note

Funding Information:
We would like to thank Rosalia Gumina of the University of The Andes for her support with the literature review.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • Phelan–McDermid syndrome
  • SHANK3
  • etiology
  • evaluation
  • treatment


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