Phelan-McDermid syndrome: a review of the literature and practice parameters for medical assessment and monitoring
Open Access
- 8 October 2014
- journal article
- review article
- Published by Springer Science and Business Media LLC in Journal of Neurodevelopmental Disorders
- Vol. 6 (1), 39
- https://doi.org/10.1186/1866-1955-6-39
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.Keywords
This publication has 64 references indexed in Scilit:
- Defects in translational regulation contributing to human cognitive and behavioral diseaseCurrent Opinion in Genetics & Development, 2011
- A copy number variation morbidity map of developmental delayNature Genetics, 2011
- Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3Human Molecular Genetics, 2011
- Shank3 mutant mice display autistic-like behaviours and striatal dysfunctionNature, 2011
- Excess of De Novo Deleterious Mutations in Genes Associated with Glutamatergic Systems in Nonsyndromic Intellectual DisabilityAmerican Journal of Human Genetics, 2011
- Clinical utility gene card for: Deletion 22q13 syndromeEuropean Journal of Human Genetics, 2010
- Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital AnomaliesAmerican Journal of Human Genetics, 2010
- 22q13.3 deletion syndrome: Clinical and molecular analysis using array CGHAmerican Journal of Medical Genetics Part A, 2010
- Contribution of SHANK3 Mutations to Autism Spectrum DisorderAmerican Journal of Human Genetics, 2007
- Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disordersNature Genetics, 2006