22q13.2q13.32 genomic regions associated with severity of speech delay, developmental delay, and physical features in Phelan–McDermid syndrome

Sarasua, Sara M.; Dwivedi, Alka; Boccuto, Luigi; Chen, Chin Fu; Sharp, Julia L.; Rollins, Jonathan D.; Collins, Julianne S.; Rogers, R. Curtis; Phelan, Katy; DuPont, Barbara R.

doi:10.1038/gim.2013.144

Cited by 80 publications

(97 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Improved understanding of the effect of neighboring genes in the region may also aid in better prediction of disease course. Although previous studies have been relatively small and report conflicting results from genotype-phenotype correlations, there is evidence from several studies that larger deletion sizes, and hence more genes affected, are associated with more severe phenotypes [10,26,61].…”

Section: Discussionmentioning

confidence: 99%

“…The reported prevalence of seizures in PMS ranges up to approximately 40 % [10,26,45,46,52,54,56,[58][59][60][61], but most case series are retrospective relying on parent report or medical record review instead of prospective analysis of electroencephalographic results. Brain magnetic resonance imaging is typically recommended because structural brain abnormalities have been reported in approximately 75 % of patients described in the literature [10,26,45,55,62].…”

Section: Medical Featuresmentioning

confidence: 99%

See 1 more Smart Citation

Phelan–McDermid Syndrome and SHANK3: Implications for Treatment

2015

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Medical Featuresmentioning

confidence: 99%

Phelan–McDermid Syndrome and SHANK3: Implications for Treatment

2015

View full text Add to dashboard Cite

“…Terminal deletions have typically nonrecurrent breakpoints and can extend up to 9 Mb (Bonaglia et al, 2011; Sarasua et al, 2014a; Soorya et al, 2013). Studies on genotype-phenotype correlations have converged on an association between the size of the deleted region and the number and/or severity of clinical manifestations (Luciani et al, 2003; Sarasua et al, 2014a; Sarasua et al, 2014b; Sarasua et al, 2011; Soorya et al, 2013; Wilson et al, 2003), although the specific findings on phenotypic variables are not completely consistent across studies. A report on 30 individuals carrying ring 22 chromosome found that the deletion size correlated with certain dysmorphic features and with the severity of developmental and speech delay (Jeffries et al, 2005).…”

Section: The Etiology Underlying Phelan Mcdermid Syndromementioning

confidence: 99%

Phelan McDermid Syndrome

et al. 2015

View full text Add to dashboard Cite

Phelan McDermid syndrome (PMS) or 22q13.3 deletion syndrome is a rare neurodevelopmental disorder characterized by generalized developmental delay, intellectual disability, absent or delayed speech, seizures, autism spectrum disorder, neonatal hypotonia, physical dysmorphic features, and recurrent medical comorbidities. In most cases, individuals with PMS have terminal deletions of the chromosomal region 22q13.3 encompassing SHANK3, a gene encoding a structural component of excitatory synapses indispensable for proper synaptogenesis and neuronal physiology. Here, we review the clinical aspects of the syndrome and the genetic findings shedding light onto the underlying etiology. We also provide an overview on the evidence from genetic studies and mouse models that supports SHANK3 haploinsufficiency as a major contributor of the neurobehavioral manifestations of PMS. Finally, we discuss how all these discoveries are uncovering the pathophysiology of PMS and are being translated into clinical trials for novel therapeutics ameliorating the core symptoms of the disorder.

show abstract

“…Syndromic autism is definied by an identified neurological disorder, harboring a set of associated phenotypes, where the genetic cause is known and gene mutation is identified. Syndromic forms of ASD are Timothy syndrome (TS), Fragile X syndrome (FXS), Angelman syndrome (AS), Prader-Willi syndrome (PWS), Phelan-McDermid and Rett syndrome (RTT) [5,[88][89][90][91] . Studies using iPSC technology have already been reported for all of these diseases.…”

Section: Autismmentioning

confidence: 99%

“…Phelan-McDermid syndrome (PMDS) is a rare disorder associated with deletions in chromosome 22q13 [91,111] . PMDS is a monogenic form of ASD with a frequency of at least 0.5% of ASD cases and is resulted by deletions in SH3 and multiple ankyrin repeat domains 3 (SHANK3) [112] .…”

Section: Phelan-mcdermid Syndromementioning

confidence: 99%