What is Phelan-McDermid syndrome?
Phelan-McDermid syndrome (PMS), also known as 22q13.3 deletion syndrome, is caused by a loss of a piece of chromosome 22 near the end of the chromosome at a location designated q13.3. The symptoms of PMS can vary from person to person but it is typically characterized by low muscle tone, global developmental delay/intellectual disability, motor skills delay, delayed or absent speech and autism spectrum disorder (ASD).
Who gets Phelan-McDermid syndrome?
There are over 1400 cases of PMS. The exact incidence is unknown.
What causes Phelan-McDermid syndrome?
PMS is caused by a deletion or mutation at the terminal end of the long arm of chromosome 22. The chromosomal region that is typically deleted contains the SHANK3 gene. As a result, people with PMS have only one copy of the SHANK3 gene in each cell rather than two copies. The SHANK3 gene provides instructions for making the SHANK3 protein that is found in many organs. It is especially important for brain functioning and development as the protein is most abundantly found there. Thus it is thought that a reduction in the amount of SHANK3 protein caused by a loss of the SHANK3 gene is responsible for many features associated with PMS.
How is Phelan-McDermid syndrome diagnosed?
There are no clinical diagnostic criteria for PMS. PMS is diagnosed through genetic testing, such as high-resolution chromosome analysis and fluorescence in situ hybridization or more commonly, chromosomal microarray or gene sequencing.
Most instances of PMS are a result of de novo chromosomal abnormality. This means that the deletion happened randomly at conception. In some cases, there is an unbalanced translocation that causes loss of SHANK3 whereas a parent has a balanced translocation without loss of SHANK3. Parental genetic testing is required to rule out balanced translocations that place subsequent offspring at risk. Chromosome analysis and prenatal testing are possible options.
What is the treatment for Phelan-McDermid syndrome?
Effective treatments are available for a variety of symptoms that occur with PMS. Medications for seizure management, behavioral interventions, and medications for anxiety and hyperactivity are available, as well as behavioral interventions, physical and occupational therapy, and speech therapy for moderating PMS symptoms.
Frequent follow-up with care providers to monitor for changes and new abnormalities is recommended.