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

doi:10.1186/1866-1955-6-39

Review

. 2014;6(1):39.

doi: 10.1186/1866-1955-6-39. Epub 2014 Oct 8.

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

Affiliations

¹ 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.
² 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.
³ 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 Neuroscience, 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.
⁴ 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 ; Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA.
⁵ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA.
⁶ Department of Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA ; Division of Endocrinology and Diabetes, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA.
⁷ Department of Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA.
⁸ Department of Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA ; Department of Cardiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA.
⁹ 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 Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA ; Division of Behavioral Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA.
¹⁰ 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 Neuroscience, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA ; Department of Genetics and Genomic Sciences, 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.

PMID: 25784960
PMCID: PMC4362650
DOI: 10.1186/1866-1955-6-39

Review

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

Alexander Kolevzon et al. J Neurodev Disord. 2014.

. 2014;6(1):39.

doi: 10.1186/1866-1955-6-39. Epub 2014 Oct 8.

Authors

Affiliations

¹ 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.
² 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.
³ 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 Neuroscience, 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.
⁴ 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 ; Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA.
⁵ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA.
⁶ Department of Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA ; Division of Endocrinology and Diabetes, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA.
⁷ Department of Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA.
⁸ Department of Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA ; Department of Cardiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA.
⁹ 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 Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA ; Division of Behavioral Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA.
¹⁰ 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 Neuroscience, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029 USA ; Department of Genetics and Genomic Sciences, 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.

PMID: 25784960
PMCID: PMC4362650
DOI: 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: 22q13 deletion syndrome; Autism; Autism spectrum disorder; Neurodevelopmental disorders; Phelan-McDermid syndrome; Practice parameters; SHANK3.

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Figures

**Figure 1**
**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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References

1. Leblond CS, Nava C, Polge A, Gauthier J, Huguet G, Lumbroso S, Giuliano F, Stordeur C, Depienne C, Mouzat K, Pinto D, Howe J, Lemière N, Durand CM, Guibert J, Ey E, Toro R, Peyre H, Mathieu A, Amsellem F, Rastam M, Gillberg IC, Rappold GA, Holt R, Monaco AP, Maestrini E, Galan P, Heron D, Jacquette A, Afenjar A, et al. Meta-analysis of SHANK mutations in autism spectrum disorders: a gradient of severity in cognitive impairments. PLoS Genet. 2014;10:e1004580. doi: 10.1371/journal.pgen.1004580. - DOI - PMC - PubMed
1. Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, Fauchereau F, Nygren G, Rastam M, Gillberg IC, Anckarsäter H, Sponheim E, Goubran-Botros H, Delorme R, Chabane N, Mouren-Simeoni MC, de Mas P, Bieth E, Rogé B, Héron D, Burglen L, Gillberg C, Leboyer M, Bourgeron T. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet. 2007;39:25–27. doi: 10.1038/ng1933. - DOI - PMC - PubMed
1. Gauthier J, Spiegelman D, Piton A, Lafrenière RG, Laurent S, St-Onge J, Lapointe L, Hamdan FF, Cossette P, Mottron L, Fombonne E, Joober R, Marineau C, Drapeau P, Rouleau GA. Novel de novo SHANK3 mutation in autistic patients. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:421–424. doi: 10.1002/ajmg.b.30822. - DOI - PubMed
1. Moessner R, Marshall CR, Sutcliffe JS, Skaug J, Pinto D, Vincent J, Zwaigenbaum L, Fernandez B, Roberts W, Szatmari P, Scherer SW. Contribution of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet. 2007;81:1289–1297. doi: 10.1086/522590. - DOI - PMC - PubMed
1. Pinto D, Delaby E, Merico D, Barbosa M, Merikangas A, Klei L, Thiruvahindrapuram B, Xu X, Ziman R, Wang Z, Vorstman JA, Thompson A, Regan R, Pilorge M, Pellecchia G, Pagnamenta AT, Oliveira B, Marshall CR, Magalhaes TR, Lowe JK, Howe JL, Griswold AJ, Gilbert J, Duketis E, Dombroski BA, De Jonge MV, Cuccaro M, Crawford EL, Correia CT, Conroy J, et al. Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am J Hum Genet. 2014;94:677–694. doi: 10.1016/j.ajhg.2014.03.018. - DOI - PMC - PubMed

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[1] Leblond CS, Nava C, Polge A, Gauthier J, Huguet G, Lumbroso S, Giuliano F, Stordeur C, Depienne C, Mouzat K, Pinto D, Howe J, Lemière N, Durand CM, Guibert J, Ey E, Toro R, Peyre H, Mathieu A, Amsellem F, Rastam M, Gillberg IC, Rappold GA, Holt R, Monaco AP, Maestrini E, Galan P, Heron D, Jacquette A, Afenjar A, et al. Meta-analysis of SHANK mutations in autism spectrum disorders: a gradient of severity in cognitive impairments. PLoS Genet. 2014;10:e1004580. doi: 10.1371/journal.pgen.1004580. - DOI - PMC - PubMed

[2] Leblond CS, Nava C, Polge A, Gauthier J, Huguet G, Lumbroso S, Giuliano F, Stordeur C, Depienne C, Mouzat K, Pinto D, Howe J, Lemière N, Durand CM, Guibert J, Ey E, Toro R, Peyre H, Mathieu A, Amsellem F, Rastam M, Gillberg IC, Rappold GA, Holt R, Monaco AP, Maestrini E, Galan P, Heron D, Jacquette A, Afenjar A, et al. Meta-analysis of SHANK mutations in autism spectrum disorders: a gradient of severity in cognitive impairments. PLoS Genet. 2014;10:e1004580. doi: 10.1371/journal.pgen.1004580. - DOI - PMC - PubMed

[3] Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, Fauchereau F, Nygren G, Rastam M, Gillberg IC, Anckarsäter H, Sponheim E, Goubran-Botros H, Delorme R, Chabane N, Mouren-Simeoni MC, de Mas P, Bieth E, Rogé B, Héron D, Burglen L, Gillberg C, Leboyer M, Bourgeron T. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet. 2007;39:25–27. doi: 10.1038/ng1933. - DOI - PMC - PubMed

[4] Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, Fauchereau F, Nygren G, Rastam M, Gillberg IC, Anckarsäter H, Sponheim E, Goubran-Botros H, Delorme R, Chabane N, Mouren-Simeoni MC, de Mas P, Bieth E, Rogé B, Héron D, Burglen L, Gillberg C, Leboyer M, Bourgeron T. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet. 2007;39:25–27. doi: 10.1038/ng1933. - DOI - PMC - PubMed

[5] Gauthier J, Spiegelman D, Piton A, Lafrenière RG, Laurent S, St-Onge J, Lapointe L, Hamdan FF, Cossette P, Mottron L, Fombonne E, Joober R, Marineau C, Drapeau P, Rouleau GA. Novel de novo SHANK3 mutation in autistic patients. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:421–424. doi: 10.1002/ajmg.b.30822. - DOI - PubMed

[6] Gauthier J, Spiegelman D, Piton A, Lafrenière RG, Laurent S, St-Onge J, Lapointe L, Hamdan FF, Cossette P, Mottron L, Fombonne E, Joober R, Marineau C, Drapeau P, Rouleau GA. Novel de novo SHANK3 mutation in autistic patients. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:421–424. doi: 10.1002/ajmg.b.30822. - DOI - PubMed

[7] Moessner R, Marshall CR, Sutcliffe JS, Skaug J, Pinto D, Vincent J, Zwaigenbaum L, Fernandez B, Roberts W, Szatmari P, Scherer SW. Contribution of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet. 2007;81:1289–1297. doi: 10.1086/522590. - DOI - PMC - PubMed

[8] Moessner R, Marshall CR, Sutcliffe JS, Skaug J, Pinto D, Vincent J, Zwaigenbaum L, Fernandez B, Roberts W, Szatmari P, Scherer SW. Contribution of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet. 2007;81:1289–1297. doi: 10.1086/522590. - DOI - PMC - PubMed

[9] Pinto D, Delaby E, Merico D, Barbosa M, Merikangas A, Klei L, Thiruvahindrapuram B, Xu X, Ziman R, Wang Z, Vorstman JA, Thompson A, Regan R, Pilorge M, Pellecchia G, Pagnamenta AT, Oliveira B, Marshall CR, Magalhaes TR, Lowe JK, Howe JL, Griswold AJ, Gilbert J, Duketis E, Dombroski BA, De Jonge MV, Cuccaro M, Crawford EL, Correia CT, Conroy J, et al. Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am J Hum Genet. 2014;94:677–694. doi: 10.1016/j.ajhg.2014.03.018. - DOI - PMC - PubMed

[10] Pinto D, Delaby E, Merico D, Barbosa M, Merikangas A, Klei L, Thiruvahindrapuram B, Xu X, Ziman R, Wang Z, Vorstman JA, Thompson A, Regan R, Pilorge M, Pellecchia G, Pagnamenta AT, Oliveira B, Marshall CR, Magalhaes TR, Lowe JK, Howe JL, Griswold AJ, Gilbert J, Duketis E, Dombroski BA, De Jonge MV, Cuccaro M, Crawford EL, Correia CT, Conroy J, et al. Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am J Hum Genet. 2014;94:677–694. doi: 10.1016/j.ajhg.2014.03.018. - DOI - PMC - PubMed

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

Affiliations

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

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