Phelan-McDermid Syndrome

What is Phelan-McDermid Syndrome?

Phelan-McDermid syndrome (also know as 22q13.3 deletion syndrome) is a rare genetic condition caused by a deletion or other structural change of the terminal end of chromosome 22 in the 22q13 region or a disease-causing mutation of the SHANK3 gene.

Although the range and severity of symptoms may vary, Phelan-McDermid syndrome is generally thought to be characterized by neonatal hypotonia (low muscle tone in the newborn), normal growth, absent to severely delayed speech, moderate to profound developmental delay, and minor dysmorphic features.

What are the symptoms of Phelan-McDermid Syndrome?

People who have Phelan-McDermid syndrome often show symptoms in very early childhood, sometimes at birth and within the first six months of life.

Symptoms may include:

Hypotonia (low or weak muscle tone)
Developmental delay (late to rolling over, sitting up, walking, or talking)
Heart defects (such as a hole in the heart)
Kidney defects
Common facial characteristics like:
- Dolichocephaly (a head shape that is longer than usual, from front to back)
- Flat midface
- Wide brow
- Wide nasal bridge
- Deep-set eyes
- Full cheeks
- Puffy eyelids
- Long eyelashes
- Bulbous nose
Seizures

About 75% have been diagnosed with an Autism Spectrum Disorder.

What causes Phelan-McDermid Syndrome?

Phelan-McDermid syndrome is caused by the deletion or disruption of the segment of the long arm (q) of chromosome 22 that is identified as 22q13.

Most cases are due to a spontaneous (de novo) break, for unknown reasons.

How is Phelan-McDermid Syndrome diagnosed?

A type of genetic test called chromosomal microarray is the most common method for diagnosing Phelan-McDermid Syndrome.

The main types of microarray technology includes:

aCGH (array comparative genomic hybridization)
SNP array (single nucleotide polymorphism)

Both of these tests will find loss or gain of chromosome material including very small changes. This means they can detect loss or gains that result from simple deletions or duplications, unbalanced translocation, ring chromosomes, and any structural change that results in a loss/gain of material.

However, these tests cannot ‘see’ the structure of the chromosome so they cannot tell if a translocation or ring chromosome is present. Fluorescence in situ hybridization (FISH) or chromosome analysis ( karyotype) may detect larger deletions and they study the structure of the chromosome.

DNA sequencing tests may detect mutations in the SHANK3 gene. Sequencing tests look for spelling errors by proofreading the letters than make up the gene.

What are the treatments for Phelan-McDermid Syndrome?

There is no cure or treatment specifically for Phelan-McDermid syndrome, but there are ways to manage many of the symptoms, per the doctor’s advice and direction.