What is Phelan-McDermid Syndrome? PDF Print E-mail

Phelan-McDermid Syndrome, sometimes called 22q13 Deletion Syndrome, is a genetic condition caused by the deletion of the terminal end of chromosome 22 or mutation of the SHANK3 gene. In most cases, the condition is not inherited, but results from a de novo (spontaneous) mutation.

What is the SHANK3 gene?

SHANK3 structurally supports synapses, the communication hubs between neurons. It gives instructions for making a protein (PROSAP2) that facilitates neuronal communication. The SHANK3 protein also helps create dendrites, which are specialized extensions from neurons that are essential for the transmission of nerve impulses.

How does the deletion happen?

The deletion can result from a simple break in the chromosome, an unbalanced translocation, a ring chromosome, or other structural changes involving chromosome 22.

Unbalanced translocation? Ring chromosome?

An unbalanced translocation occurs when a piece of one chromosome breaks off and reattaches to another chromosome. A ring chromosome is caused when the two ends of a chromosome fuse together, creating a circle.

What are the core features of PMS?

The most common characteristics found in those with PMS are intellectual disability of varying degrees, delayed or absent speech, symptoms of autism spectrum disorder, low muscle tone, motor delays and epilepsy.

Are all cases of PMS the same?

Deletion sizes, SHANK3 gene mutations and the clinical features of Phelan-McDermid Syndrome are all highly variable. Nonetheless, studies suggest that individuals with larger deletions are more likely than those with smaller deletions to have characteristic body features, neonatal hypotonia, neonatal feeding problems, atypical reflexes and greater delays in meeting developmental milestones.

How are cases of PMS diagnosed?

Chromosomal microarray (including array comparative genomic hybridization [CGH] and SNP microarray), is the most common method for diagnosing Phelan-McDermid Syndrome. Fluorescence in situ hybridization (FISH) or chromosome analysis may detect larger deletions and are necessary to identify translocations and ring chromosomes. If a diagnosis of Phelan-McDermid Syndrome is suspected, but no deletion of 22q13 is detected through microarray, targeted DNA sequencing may detect mutations of the SHANK3 gene.

What’s needed for testing?

Deletions, rings, translocations and mutations can be detected from blood samples as well as from skin cells or cells used for prenatal testing.

How many cases of PMS are there?

We're not sure and we don't have a reliable estimate. There are cases that we don't know about or that have not been diagnosed using the most sophisticated chromosomal testing.

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