Updated consensus guidelines on the management of Phelan-McDermid syndrome

Siddharth Srivastava; Mustafa Sahin; Joseph D Buxbaum; Elizabeth Berry-Kravis; Latha Valluripalli Soorya; Audrey Thurm; Jonathan A Bernstein; Afua Asante-Otoo; William E Bennett Jr; Catalina Betancur; Tegwyn H Brickhouse; Maria Rita Passos Bueno; Maya Chopra; Celanie K Christensen; Jennifer L Cully; Kira Dies; Kate Friedman; Brittany Gummere; J Lloyd Holder Jr; Andres Jimenez-Gomez; Carolyn A Kerins; Omar Khan; Teresa Kohlenberg; Ronald V Lacro; Lori A Levi; Tess Levy; Diane Linnehan; Loth Eva; Baharak Moshiree; Ann Neumeyer; Scott M Paul; Katy Phelan; Antonio Persico; Robert Rapaport; Curtis Rogers; Jeffrey Saland; Swathi Sethuram; Janine Shapiro; Phillip I Tarr; Kerry M White; Jordan Wickstrom; Kent M Williams; Dana Winrow; Brian Wishart; Alexander Kolevzon

doi:10.1002/ajmg.a.63312

Updated consensus guidelines on the management of Phelan-McDermid syndrome

Am J Med Genet A. 2023 Aug;191(8):2015-2044. doi: 10.1002/ajmg.a.63312. Epub 2023 Jul 1.

Authors

Siddharth Srivastava^{1

2}, Mustafa Sahin^{1

2}, Joseph D Buxbaum^{3

4

5

6}, Elizabeth Berry-Kravis^{7

8

9}, Latha Valluripalli Soorya¹⁰, Audrey Thurm¹¹, Jonathan A Bernstein¹², Afua Asante-Otoo¹³, William E Bennett Jr¹⁴, Catalina Betancur¹⁵, Tegwyn H Brickhouse¹⁶, Maria Rita Passos Bueno¹⁷, Maya Chopra^{1

2}, Celanie K Christensen^{18

19}, Jennifer L Cully²⁰, Kira Dies^{1

2}, Kate Friedman^{3

4}, Brittany Gummere²¹, J Lloyd Holder Jr²², Andres Jimenez-Gomez²³, Carolyn A Kerins²⁴, Omar Khan²⁵, Teresa Kohlenberg²⁶, Ronald V Lacro²⁷, Lori A Levi²⁸, Tess Levy³, Diane Linnehan²⁹, Loth Eva³⁰, Baharak Moshiree³¹, Ann Neumeyer³², Scott M Paul¹³, Katy Phelan³³, Antonio Persico³⁴, Robert Rapaport³⁵, Curtis Rogers³⁶, Jeffrey Saland³⁵, Swathi Sethuram³⁷, Janine Shapiro³⁸, Phillip I Tarr³⁹, Kerry M White^{18

40}, Jordan Wickstrom⁴¹, Kent M Williams⁴², Dana Winrow⁴³, Brian Wishart⁴⁴, Alexander Kolevzon^{3

4

35}

Affiliations

¹ Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, USA.
² Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³ Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁴ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁵ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁶ Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁷ Department of Pediatrics, Rush University Medical Center, Chicago, Illinois, USA.
⁸ Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
⁹ Department of Biochemistry, Rush University Medical Center, Chicago, Illinois, USA.
¹⁰ Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, Illinois, USA.
¹¹ Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
¹² Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.
¹³ Rehabilitation Medicine Department, NIH Clinical Center, Bethesda, Maryland, USA.
¹⁴ Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹⁵ Sorbonne Université, INSERM, CNRS, Neuroscience Paris Seine, Institut de Biologie Paris Seine, Paris, France.
¹⁶ Department of Dental Public Health & Policy, School of Dentistry, Virginia Commonwealth University, Richmond, Virginia, USA.
¹⁷ Departamento de Genética e Biologia Evolutiva, Centro de Estudos do Genoma Humano e Células-tronco, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
¹⁸ Division of Developmental Medicine, Department of Pediatrics, Riley Children's Health, Indianapolis, Indiana, USA.
¹⁹ Division of Child Neurology, Department of Neurology, Riley Children's Health, Indianapolis, Indiana, USA.
²⁰ Department of Pediatrics, College of Medicine and Division of Dentistry and Orthodontics, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
²¹ Indiana University, Indianapolis, Indiana, USA.
²² Department of Pediatrics-Neurology, Baylor College of Medicine, Houston, Texas, USA.
²³ Joe DiMaggio Children's Hospital, Hollywood, Florida, USA.
²⁴ Department of Pediatric Dentistry, School of Dentistry, Texas A&M University, Dallas, Texas, USA.
²⁵ National Institute of Neurological Disease and Stroke, Bethesda, Maryland, USA.
²⁶ University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
²⁷ Department of Cardiology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
²⁸ University of Southern California, Arcadia, California, USA.
²⁹ Phelan-McDermid Syndrome Foundation, Osprey, Florida, USA.
³⁰ Kings College London, London, UK.
³¹ Department of Medicine, Wake Forest/Atrium Health, Charlotte, North Carolina, USA.
³² Lurie Center for Autism, Massachusetts General Hospital, Lexington, Massachusetts, USA, Harvard Medical School, Boston, Massachusetts, USA.
³³ Genetics Laboratory, Florida Cancer Specialists and Research Institute, Fort Myers, Florida, USA.
³⁴ Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
³⁵ Department of Pediatrics, Kravis Children's Hospital, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
³⁶ RCR Genetics, Greer, South Carolina, USA.
³⁷ Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA.
³⁸ Access Behavior Analysis, Indianapolis, Indiana, USA.
³⁹ Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
⁴⁰ Department of Medical and Molecular Genetics, Riley Children's Health, Indianapolis, Indiana, USA.
⁴¹ Sinai Rehabilitation Center, Lifebridge Health, Baltimore, Maryland, USA.
⁴² Department of Pediatrics, The Ohio State University School of Medicine, Columbus, Ohio, USA.
⁴³ Emerson Health, Concord, Massachusetts, USA.
⁴⁴ Massachusetts General Hospital, Boston, Massachusetts, USA.

Abstract

Phelan-McDermid syndrome (PMS) is a genetic condition caused by SHANK3 haploinsufficiency and characterized by a wide range of neurodevelopmental and systemic manifestations. The first practice parameters for assessment and monitoring in individuals with PMS were published in 2014; recently, knowledge about PMS has grown significantly based on data from longitudinal phenotyping studies and large-scale genotype-phenotype investigations. The objective of these updated clinical management guidelines was to: (1) reflect the latest in knowledge in PMS and (2) provide guidance for clinicians, researchers, and the general community. A taskforce was established with clinical experts in PMS and representatives from the parent community. Experts joined subgroups based on their areas of specialty, including genetics, neurology, neurodevelopment, gastroenterology, primary care, physiatry, nephrology, endocrinology, cardiology, gynecology, and dentistry. Taskforce members convened regularly between 2021 and 2022 and produced specialty-specific guidelines based on iterative feedback and discussion. Taskforce leaders then established consensus within their respective specialty group and harmonized the guidelines. The knowledge gained over the past decade allows for improved guidelines to assess and monitor individuals with PMS. Since there is limited evidence specific to PMS, intervention mostly follows general guidelines for treating individuals with developmental disorders. Significant evidence has been amassed to guide the management of comorbid neuropsychiatric conditions in PMS, albeit mainly from caregiver report and the experience of clinical experts. These updated consensus guidelines on the management of PMS represent an advance for the field and will improve care in the community. Several areas for future research are also highlighted and will contribute to subsequent updates with more refined and specific recommendations as new knowledge accumulates.

Keywords: Phelan-McDermid syndrome; SHANK3; assessment; autism spectrum disorder; monitoring; treatment.

Publication types

Review
Research Support, N.I.H., Extramural

MeSH terms

Chromosome Deletion
Chromosome Disorders* / diagnosis
Chromosome Disorders* / epidemiology
Chromosome Disorders* / genetics
Chromosomes, Human, Pair 22 / genetics
Humans
Nerve Tissue Proteins / genetics
Phenotype

Updated consensus guidelines on the management of Phelan-McDermid syndrome

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