Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder with non-specific clinical features. The main symptoms are hypotonia, intellectual disability (ID), absent or delayed speech together with minor dysmorphic features.
More than half of the patients exhibit autism spectrum disorders (ASD). PMS is a contiguous gene syndrome resulting from deletion of the distal long arm of chromosome 22.
The type and the size of the deletion can vary from one patient to another. In the vast majority of the cases, the deletion is de novo.

There is a gradient of severity in PMS. Some patients have difficulty to walk or may have a severe intellectual disability while other patients can speak and go to high school.

The size of the deletion seems to contribute to the presence of some features (speech problems are more frequent in patients with large deletions). In contrast, seizures, hypotonia, birth weight, and gestational age at birth do not seem to correlate with deletion size.

Among the genes located at 22q13, we previously identified deleterious de novo mutations of the SHANK3 gene in patients with ASD and ID. SHANK3 codes for a synaptic scaffolding protein that plays an important role in the formation of dendrites and glutamatergic synapses. While SHANK3 has been extensively studied as a candidate gene for the neurological symptoms of PMS, it is clear that many other genes in the region are involved in the pathogenesis of PMS.

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