Phelan-McDermid syndrome

=Phelan-McDermid Syndrome = Phelan-McDermid Syndrome (PMS), also known as 22q13 deletion syndrome, is a rare genetic disorder caused by the deletion or mutation of the terminal end of chromosome 22. This condition is characterized by developmental delay, intellectual disability, and absent or severely delayed speech.

Genetics

Phelan-McDermid Syndrome is typically caused by a deletion of the terminal end of chromosome 22, specifically at the 22q13.3 region. This deletion affects the SHANK3 gene, which is crucial for synaptic function and neuronal communication. In some cases, mutations in the SHANK3 gene without a deletion can also lead to PMS.

SHANK3 Gene

The SHANK3 gene encodes a protein that is part of the postsynaptic density in neurons. This protein plays a critical role in the formation and maintenance of synapses, which are essential for communication between neurons. Disruption of SHANK3 can lead to the neurological and developmental symptoms observed in PMS.

Symptoms

Individuals with Phelan-McDermid Syndrome may exhibit a range of symptoms, including:

• Developmental delay
• Intellectual disability
• Absent or delayed speech
• Hypotonia (low muscle tone)
• Motor skill deficits
• Behavioral issues, such as autism spectrum disorder-like behaviors
• Sleep disturbances

Diagnosis

Diagnosis of PMS is typically confirmed through genetic testing, such as chromosomal microarray analysis or whole exome sequencing, which can identify deletions or mutations in the 22q13 region.

Management

There is currently no cure for Phelan-McDermid Syndrome. Management focuses on addressing the symptoms and may include:

• Speech therapy
• Occupational therapy
• Physical therapy
• Behavioral interventions
• Educational support

Research

Ongoing research is focused on understanding the role of the SHANK3 gene in neuronal function and exploring potential therapeutic approaches. Studies are also investigating the broader genetic and phenotypic spectrum of PMS.

See Also

• Chromosome 22
• Genetic Disorders
• Autism Spectrum Disorder
• Phelan, K., & McDermid, H. E. (2012). The 22q13.3 Deletion Syndrome (Phelan-McDermid Syndrome). Molecular Syndromology, 2(3-5), 186-201.
• Wilson, H. L., Wong, A. C., Shaw, S. R., Tse, W. Y., Stapleton, G. A., Phelan, M. C., ... & Marshall, J. (2003). Molecular characterization of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3/PROSAP2 in the major neurological symptoms. Journal of Medical Genetics, 40(8), 575-584.

NIH genetic and rare disease info

• NIH info on Phelan-McDermid syndrome

Phelan-McDermid syndrome is a rare disease.