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

Kolevzon A, Angarita B, Bush L, Wang AT, Frank Y, Yang A, Rapaport R, Saland J, Srivastava S, Farrell C, Edelmann LJ, Buxbaum JD - J Neurodev Disord (2014)

Bottom Line: SHANK3 is the critical gene in this syndrome, and its loss results in disruption of synaptic function.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.

View Article: PubMed Central - PubMed

Affiliation: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA ; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA ; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA ; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA ; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA.

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.

No MeSH data available.


Related in: MedlinePlus

Images of individuals with Phelan-McDermid syndrome illustrating common dysmorphic facial features, including long eyelashes, bulbous nose, and pointed chin. All images are provided with guardian consent.
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Fig1: Images of individuals with Phelan-McDermid syndrome illustrating common dysmorphic facial features, including long eyelashes, bulbous nose, and pointed chin. All images are provided with guardian consent.

Mentions: Clinical genetics evaluations and dysmorphology exams should be performed by a clinical geneticist to assess growth, pubertal development, head size, craniofacial features, digits, extremities, chest, spine, skin, and screen for organ malformations (such as congenital heart or renal defects). Most patients with PMS have at least one dysmorphic feature, although none are specific. The most common features are large fleshy hands, long eyelashes, pointed chin, prominent/dysplastic ears, bulbous nose, full lips, hypoplastic/dysplastic nails, and dolichocephaly (see Figure 1 and Table 1). All images are provided with guardian consent.Figure 1


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

Kolevzon A, Angarita B, Bush L, Wang AT, Frank Y, Yang A, Rapaport R, Saland J, Srivastava S, Farrell C, Edelmann LJ, Buxbaum JD - J Neurodev Disord (2014)

Images of individuals with Phelan-McDermid syndrome illustrating common dysmorphic facial features, including long eyelashes, bulbous nose, and pointed chin. All images are provided with guardian consent.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4362650&req=5

Fig1: Images of individuals with Phelan-McDermid syndrome illustrating common dysmorphic facial features, including long eyelashes, bulbous nose, and pointed chin. All images are provided with guardian consent.
Mentions: Clinical genetics evaluations and dysmorphology exams should be performed by a clinical geneticist to assess growth, pubertal development, head size, craniofacial features, digits, extremities, chest, spine, skin, and screen for organ malformations (such as congenital heart or renal defects). Most patients with PMS have at least one dysmorphic feature, although none are specific. The most common features are large fleshy hands, long eyelashes, pointed chin, prominent/dysplastic ears, bulbous nose, full lips, hypoplastic/dysplastic nails, and dolichocephaly (see Figure 1 and Table 1). All images are provided with guardian consent.Figure 1

Bottom Line: SHANK3 is the critical gene in this syndrome, and its loss results in disruption of synaptic function.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.

View Article: PubMed Central - PubMed

Affiliation: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA ; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA ; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA ; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA ; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA.

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.

No MeSH data available.


Related in: MedlinePlus