Deletion 22q13.3 syndrome

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 autisticlike 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 autisticlike 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.

Phelan–McDermid Syndrome and SHANK3: Implications for Treatment

“…In addition, up to 2 % of ASD with moderate-to-profound ID can be explained by loss of SHANK3 [38,39]. Men and women appear to be equally affected by PMS [40]. Many other areas of epidemiological study are currently underway, including attempts to better understand the impact of neighboring genes on phenotypic heterogeneity and severity.…”

“…Very small intragenic deletions (<30 kb) and mutations will not be identified by CMA and require DNA sequencing techniques to evaluate individual base pairs within the gene [42]. Although the majority of cases of PMS are caused by de novo terminal deletions of chromosome 22, approximately 20 % of parents may carry a balanced translocation that results in an unbalanced rearrangement in the affected child and requires chromosome analysis (i.e., karyotype) for detection [40]. Biological parents always require testing to rule out inversions or translocations, and to clarify recurrence risk within families.…”

Síndrome de Phelan-McDermid: reporte de un caso y revisión de la literatura

“…Las deleciones intragé-nicas menores a 30 kb no se pueden identificar mediante microarreglos y deberá realizarse secuenciación. 1,2,4,8 En el presente caso no se realizó el estudio de microarreglos de primera intención, se inició con el cariotipo con lo cual fue posible establecer la alteración estructural y posteriormente confirmar el diagnóstico mediante las diferentes metodologías antes mencionas.…”

Phelan‐McDermid syndrome data network: Integrating patient reported outcomes with clinical notes and curated genetic reports

“…One such rare neuropsychiatric disorder is Phelan‐McDermid Syndrome (PMS) or 22q13 deletion syndrome (OMIM 606232) (Cusmano‐Ozog, Manning, & Eugene Hoyme, 2007; Phelan, 2008; Phelan & McDermid, 2012), with approximately 1,400 cases diagnosed worldwide, mostly in children. PMS is caused by deletion of the terminal end of the long arm of chromosome 22 or by mutation and loss of function of the SHANK3 gene (Macedoni‐Lukšič, Krgović, Zagradišnik, & Kokalj‐Vokač, 2013), which is also implicated in ASD (Gauthier et al, 2008; Uchino & Waga, 2013).…”