Phelan-McDermid syndrome: A review of the literature and practice parameters for medical assessment and monitoring

Alexander Kolevzon, Benjamin Angarita, Lauren Bush, A. Ting Wang, Yitzchak Frank, Amy Yang, Robert Rapaport, Jeffrey Saland, Shubhika Srivastava, Cristina Farrell, Lisa J. Edelmann, Joseph D. Buxbaum

Research output: Contribution to journalReview article

48 Scopus citations

Abstract

Autism spectrum disorder (ASD) and intellectual disability (ID) can be caused by mutations in a large number of genes. One example is SHANK3 on the terminal end of chromosome 22q. Loss of one functional copy of SHANK3 results in 22q13 deletion syndrome or Phelan-McDermid syndrome (PMS) and causes a monogenic form of ASD and/or ID with a frequency of 0.5% to 2% of cases. SHANK3 is the critical gene in this syndrome, and its loss results in disruption of synaptic function. With chromosomal microarray analyses now a standard of care in the assessment of ASD and developmental delay, and with the emergence of whole exome and whole genome sequencing in this context, identification of PMS in routine clinical settings will increase significantly. However, PMS remains a rare disorder, and the majority of physicians have never seen a case. While there is agreement about core deficits of PMS, there have been no established parameters to guide evaluation and medical monitoring of the syndrome. Evaluations must include a thorough history and physical and dysmorphology examination. Neurological deficits, including the presence of seizures and structural brain abnormalities should be assessed as well as motor deficits. Endocrine, renal, cardiac, and gastrointestinal problems all require assessment and monitoring in addition to the risk of recurring infections, dental and vision problems, and lymphedema. Finally, all patients should have cognitive, behavioral, and ASD evaluations. The objective of this paper is to address this gap in the literature and establish recommendations to assess the medical, genetic, and neurological features of PMS.

Original languageEnglish (US)
Article number39
JournalJournal of Neurodevelopmental Disorders
Volume6
Issue number1
DOIs
StatePublished - Oct 8 2014
Externally publishedYes

Keywords

  • 22q13 deletion syndrome
  • Autism
  • Autism spectrum disorder
  • Neurodevelopmental disorders
  • Phelan-McDermid syndrome
  • Practice parameters
  • SHANK3

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cognitive Neuroscience

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    Kolevzon, A., Angarita, B., Bush, L., Wang, A. T., Frank, Y., Yang, A., Rapaport, R., Saland, J., Srivastava, S., Farrell, C., Edelmann, L. J., & Buxbaum, J. D. (2014). Phelan-McDermid syndrome: A review of the literature and practice parameters for medical assessment and monitoring. Journal of Neurodevelopmental Disorders, 6(1), [39]. https://doi.org/10.1186/1866-1955-6-39