Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Microdeletion 22q13.3 (Phelan-McDermid Syndrome) [Q93]

OMIM number: 606232

Dr. med. Imma Rost

Scientific Background

The microdeletion 22q13.3 affects the terminal end of the long arm of chromosome 22, not the region 22q11.2 known from the context of the DiGeorge syndrome. Some patients have deletions detectable under the light microscope, others very small deletions that can be detected by FISH analysis or array CGH. In approximately a third of all cases, the deletion is a consequence of a chromosomal translocation.

The major sign of the deletion 22q13.3 is a marked muscular hypotonia, which is usually already present in the newborn. Therefore, this microdeletion can be included in the differential diagnosis of a severe hypotonia occurring in newborns. Moreover, a developmental delay mainly affecting speech develops later on, potentially a lack of expressive speech. Normal or above-average body size is characteristical. Some patients show autistic behaviour. There are minor dysmorphic features that are uncharacteristic and seem to vary according to the size of the deletion: dolichocephaly, dysplastic ears, epicanthal fold, ptosis, periorbital fullness, smooth philtrum, full lips, pointed chin, syndactyly of the toes II-III, dysplastic toenails. Slightly less than a third of all patients suffer from seizures.

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