Deletion 22q13.3 syndrome

Phelan, Mary C

doi:10.1186/1750-1172-3-14

Cited by 221Genomic variations and chromosomal abnormalitiesGenetics and Neurodevelopmental DisordersGenomics and Rare Diseases

Deletion 22q13.3 syndrome

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Phelan, Mary C·2008·Orphanet Journal of Rare Diseases

DOI 10.1186/1750-1172-3-14PMC PMC2427010

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Abstract

The deletion 22q13.3 syndrome (deletion 22q13 syndrome or Phelan-McDermid syndrome) is a chromosome microdeletion syndrome characterized by neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, and minor dysmorphic features. The deletion occurs with equal frequency in males and females and has been reported in mosaic and non-mosaic forms. Due to lack of clinical recognition and often insufficient laboratory testing, the syndrome is under-diagnosed and its true incidence remains unknown. Common physical traits include long eye lashes, large or unusual ears, relatively large hands, dysplastic toenails, full brow, dolicocephaly, full cheeks, bulbous nose, and pointed chin. Behavior is autistic-like with decreased perception of pain and habitual chewing or mouthing. The loss of 22q13.3 can result from simple deletion, translocation, ring chromosome formation and less common structural changes affecting the long arm of chromosome 22, specifically the region containing the SHANK3 gene. The diagnosis of deletion 22q13 syndrome should be considered in all cases of hypotonia of unknown etiology and in individuals with absent speech. Although the deletion can sometimes be detected by high resolution chromosome analysis, fluorescence in situ hybridization (FISH) or array comparative genomic hybridization (CGH) is recommended for confirmation. Differential diagnosis includes syndromes associated with hypotonia, developmental delay, speech delay and/or autistic-like affect (Prader-Willi, Angelman, Williams, Smith-Magenis, Fragile X, Sotos, FG, trichorhinophalangeal and velocardiofacial syndromes, autism spectrum disorders, cerebral palsy). Genetic counseling is recommended and parental laboratory studies should be considered to identify cryptic rearrangements and detect parental mosaicism. Prenatal diagnosis should be offered for future pregnancies in those families with inherited rearrangements. Individuals with deletion 22q13 should have routine examinations by the primary care physician as well as genetic evaluations with referral to specialists if neurological, gastrointestinal, renal, or other systemic problems are suspected. Affected individuals benefit from early intervention programs, intense occupational and communication therapies, adaptive exercise and sport programs, and other therapies to strengthen their muscles and increase their communication skills. No apparent life-threatening organic abnormalities accompany the diagnosis of deletion 22q13.

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Excessive mGluR5 signaling has been implicated in fragile X syndrome, which has clinical overlap with 22q13.3 deletions.
“although excessive mGluR5 signaling has been implicated in fragile X syndrome (Krueger and Bear, 2011), which has clinical overlap with 22q13.3 deletions (Phelan, 2008).”
From Modeling Autism by SHANK Gene Mutations in Mice (2013) · cites this paper as Phelan, 2008

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Authors: Phelan, M. C.
Affiliations: Molecular Pathology Laboratory Network (United States) (US)
Corresponding author: Phelan, Mary C
Venue: Orphanet Journal of Rare Diseases
Publisher: Springer Science and Business Media LLC
Published: 2008-05-27
Volume: 3
Issue: 1
Pages: 14-14
ISSN: 1750-1172 (ISSN-L)
DOI: 10.1186/1750-1172-3-14
PMC: PMC2427010
OpenAlex: W2061869968
Cited by: 221
References: 20
Citations by year: 2026: 2 · 2025: 7 · 2024: 2 · 2023: 4 · 2022: 9 · 2021: 9 · 2020: 12 · 2019: 6 · 2018: 9 · 2017: 10 · 2016: 15 · 2015: 7 · 2014: 15 · 2013: 15 · 2012: 20
FWCI: 14.82
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/2.0 (tdm)
Locations: Orphanet Journal of Rare Diseases (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords: Phelan-McDermid syndrome, 22q13.3 deletion, SHANK3, hypotonia, developmental delay, speech delay, autism-like behavior, dysmorphic features, prenatal diagnosis, genetic counseling, differential diagnosis, early intervention, mosaicism
MeSH terms: Carrier Proteins, Child, Developmental Disabilities, Chromosome Deletion, Chromosomes, Human, Pair 22, Diagnosis, Differential, Genetic Counseling, Humans, Nerve Tissue Proteins, Prenatal Diagnosis, Prognosis, Speech Disorders, Syndrome, In Situ Hybridization, Fluorescence

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Deletion 22q13.3 syndrome

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