MICRODELETION 22q13.3 (PHELAN MCDERMID SYNDROME)

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Description

Scientific background

Microdeletion 22q13.3 affects the terminal end of the long arm of chromosome 22 which is not the region 22q11.2 known from DiGeorge syndrome. Some patients have deletions detectable by light microscopy, while others have deletions that can only be detected by FISH analysis or CMA (chromosomal microarray). In approximately one third of patients, the deletion is a consequence of a chromosomal translocation.

 

The leading symptom of deletion 22q13.3 is a pronounced muscle hypotonia which is usually already present in a newborn. Therefore, this microdeletion can be included as a differential diagnosis of severe hypotonia in a newborn. In addition, a developmental delay occurs later on which mainly affects speech and may even lead to the absence of expressive speech. Normal to large body measurements are characteristic. Autistic behavior has been described in some patients. External features are discrete and inconspicuous and seem to vary depending on the size of the deletion: dolichocephaly, auricular dysplasia, epicanthus, ptosis, periorbital soft tissue fullness, deformed philtrum, full lips, pronounced chin, syndactyly of toes II-III, dysplastic toenails. Seizures occur in nearly one third.

 

The smallest overlapping deletion region contains the SHANK3/ProSAP2 gene whose haploinsufficiency is thought to cause most of the neurological symptoms of Phelan-McDermid syndrome. The gene product functions as a scaffolding protein in postsynaptic structures of excitatory synapses and binds to neuroligins that are also associated with autistic disorders.

 

References

Harony-Nicolas et al. 2015, J Child Neurol 30(14):1861 / Sykes NH et al. 2009, EJHG 17 :1347 / Phelan MC 2008, OJRD 3 :14 / Cusmano-Ozog K et al. 2007, AM J Med Genet 145C :393 / Lindquist SG et al. 2005, Clin Dysmorphol 14:55 / Manning MA et al. 2004, Pediatrics 114, 2:451 / Phelan MC et al. 2001, Am J Med Genet 101:91

GENES

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