Sleep disturbances in Phelan‐McDermid syndrome: Clinical and metabolic profiling of 56 individuals
Phelan‐McDermid Syndrome (PMS) is caused by deletions at chromosome 22q13.3 or pathogenic/likely pathogenic SHANK3 variants. The clinical presentation is extremely variable and includes global developmental delay/intellectual disability (ID), seizures, neonatal hypotonia, and sleep disturbances, amo...
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Published in | Clinical genetics Vol. 104; no. 2; pp. 198 - 209 |
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Main Authors | , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Publishing Ltd
01.08.2023
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Subjects | |
Online Access | Get full text |
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Summary: | Phelan‐McDermid Syndrome (PMS) is caused by deletions at chromosome 22q13.3 or pathogenic/likely pathogenic SHANK3 variants. The clinical presentation is extremely variable and includes global developmental delay/intellectual disability (ID), seizures, neonatal hypotonia, and sleep disturbances, among others. This study investigated the prevalence of sleep disturbances, and the genetic and metabolic features associated with them, in a cohort of 56 individuals with PMS. Sleep data were collected via standardized observer/caregiver questionnaires, while genetic data from array‐CGH and sequencing of 9 candidate genes within the 22q13.3 region, and metabolic profiling utilized the Biolog Phenotype Mammalian MicroArray plates. Sleep disturbances were present in 64.3% of individuals with PMS, with the most common problem being waking during the night (39%). Sleep disturbances were more prevalent in individuals with a SHANK3 pathogenic variant (89%) compared to subjects with 22q13.3 deletions of any size (59.6%). Distinct metabolic profiles for individuals with PMS with and without sleep disturbances were also identified. These data are helpful information for recognizing and managing sleep disturbances in individuals with PMS, outlining the main candidate gene for this neurological manifestation, and highlighting potential biomarkers for early identification of at‐risk subjects and molecular targets for novel treatment approaches. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author Contributions BAM wrote and submitted the manuscript. BAM, LB, and SMS formulated the paper and created the research design. LMO and L. Beamer collected clinical data from patients. LJ, SS, CK, KJ, MM, LC, and BD transformed blood samples into LCLs, collected Biolog data, and sequenced available patient samples. RCR, KP, WEK, SMS, and LB reviewed the manuscript. All authors have read and agreed to the published version of the manuscript. |
ISSN: | 0009-9163 1399-0004 1399-0004 |
DOI: | 10.1111/cge.14361 |