Browsing by Subject "Phelan-McDermid syndrome"

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    Phelan-McDermid syndrome: a classification system after 30 years of experience
    (BMC, 2022-01-29) Phelan, Katy; Boccuto, Luigi; Powell, Craig M.; Boeckers, Tobias M.; van Ravenswaaij‑Arts, Conny; Rogers, R. Curtis; Sala, Carlo; Verpelli, Chiara; Thurm, Audrey; Bennett, William E., Jr.; Winrow, Christopher J.; Garrison, Sheldon R.; Toro, Roberto; Bourgeron, Thomas; Pediatrics, School of Medicine
    Phelan-McDermid syndrome (PMS) was initially called the 22q13 deletion syndrome based on its etiology as a deletion of the distal long arm of chromosome 22. These included terminal and interstitial deletions, as well as other structural rearrangements. Later, pathogenetic variants and deletions of the SHANK3 gene were found to result in a phenotype consistent with PMS. The association between SHANK3 and PMS led investigators to consider disruption/deletion of SHANK3 to be a prerequisite for diagnosing PMS. This narrow definition of PMS based on the involvement of SHANK3 has the adverse effect of causing patients with interstitial deletions of chromosome 22 to "lose" their diagnosis. It also results in underreporting of individuals with interstitial deletions of 22q13 that preserve SHANK3. To reduce the confusion for families, clinicians, researchers, and pharma, a simple classification for PMS has been devised. PMS and will be further classified as PMS-SHANK3 related or PMS-SHANK3 unrelated. PMS can still be used as a general term, but this classification system is inclusive. It allows researchers, regulatory agencies, and other stakeholders to define SHANK3 alterations or interstitial deletions not affecting the SHANK3 coding region.
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    Updated Consensus Guidelines on the Management of Phelan-McDermid Syndrome
    (Wiley, 2023) Srivastava, Siddharth; Sahin, Mustafa; Buxbaum, Joseph D.; Berry-Kravis, Elizabeth; Valluripalli Soorya, Latha; Thurm, Audrey; Bernstein, Jonathan A.; Asante-Otoo, Afua; Bennett, William E., Jr.; Betancur, Catalina; Brickhouse, Tegwyn H.; Bueno, Maria Rita Passos; Chopra, Maya; Christensen, Celanie K.; Cully, Jennifer L.; Dies, Kira; Friedman, Kate; Gummere, Brittany; Holder, J. Lloyd, Jr.; Jimenez-Gomez, Andres; Kerins, Carolyn A.; Khan, Omar; Kohlenberg, Teresa; Lacro, Ronald V.; Levi, Lori A.; Levy, Tess; Linnehan, Diane; Loth, Eva; Moshiree, Baharak; Neumeyer, Ann; Paul, Scott M.; Phelan, Katy; Persico, Antonio; Rapaport, Robert; Rogers, Curtis; Saland, Jeffrey; Sethuram, Swathi; Shapiro, Janine; Tarr, Phillip I.; White, Kerry M.; Wickstrom, Jordan; Williams, Kent M.; Winrow, Dana; Wishart, Brian; Kolevzon, Alexander; Pediatrics, School of Medicine
    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.