What is 22q13 deletion / Phelan-McDermid Syndrome

TL;DR: Phelan-McDermid syndrome (also known as 22q13 deletion syndrome) is a rare genetic condition caused by the loss of a specific segment of the 22nd chromosome, leading to global developmental delays, absent or delayed speech, and autism spectrum features. Currently, 35 people living with Phelan-McDermid syndrome have shared their journeys on DiseaseMaps.org, providing a vital network of support for families navigating this diagnosis.

What causes Phelan-McDermid syndrome?

Phelan-McDermid syndrome is primarily caused by a deletion or mutation involving the terminal end of the long arm (q) of chromosome 22. This specific region contains the SHANK3 gene, which is critical for the development and function of synapses—the connections between nerve cells in the brain. When this gene is missing or disrupted, the brain struggles to communicate effectively, which explains why Phelan-McDermid syndrome is so closely linked to intellectual disability and communication challenges. In most cases, the deletion happens spontaneously (de novo) during the formation of reproductive cells, though it can occasionally be inherited from a parent who carries a balanced chromosomal rearrangement.

How does 22q13 deletion affect the body?

Because the genetic loss in 22q13 deletion affects fundamental brain development, the symptoms are widespread. While every individual’s experience is unique, the clinical presentation often includes:

• Significant speech delays: Many individuals with Phelan-McDermid syndrome have little to no expressive language.


• Hypotonia: Low muscle tone is common, often appearing in infancy and potentially causing delays in motor milestones like sitting or walking.


• Neurological differences: A high prevalence of epilepsy and an increased risk for autism spectrum disorder.


• Physical traits: Some individuals may have distinctive facial features, such as deep-set eyes, full eyelids, or large, fleshy hands.


• Gastrointestinal and sensory issues: Many children experience chronic constipation, sensory processing differences, or a decreased sensitivity to pain.

How common is Phelan-McDermid syndrome?

Phelan-McDermid syndrome is considered a rare disease, though its exact prevalence remains difficult to determine because it is frequently underdiagnosed or misdiagnosed as generalized autism. Estimates suggest the incidence may be as high as 1 in 8,000 to 15,000 births. Because the condition is genetic, it affects all genders and ethnicities equally. There is no geographic bias, as the condition arises from random genetic events rather than environmental factors.

What differentiates this from other conditions?

While 22q13 deletion shares symptoms with other neurodevelopmental disorders, the specific involvement of the SHANK3 gene provides a unique diagnostic signature. Unlike some other autism-related genetic conditions, Phelan-McDermid syndrome is often characterized by a lack of regression; developmental progress is typically slow but steady. Furthermore, the physical markers, such as the unique nail structure (dysplastic toenails) and the specific pattern of hypotonia, help clinicians distinguish this from idiopathic autism.

Next steps

• Consult a geneticist: A clinical geneticist can confirm the diagnosis through chromosomal microarray analysis.


• Build a care team: Seek specialists in neurology (for seizure management), speech therapy, and occupational therapy.


• Join the community: Connect with others by visiting the Phelan-McDermid syndrome community on DiseaseMaps.org to share experiences and resources.


• Stay informed: Follow updates from the Phelan-McDermid Syndrome Foundation regarding emerging clinical trials and research.

Medical disclaimer: This information is for educational purposes only and does not constitute professional medical advice, diagnosis, or treatment; always seek the advice of your physician or other qualified health provider with any questions regarding a medical condition.

References

• NIH GARD: Phelan-McDermid syndrome (https://rarediseases.info.nih.gov/)


• Orphanet: 22q13.3 deletion syndrome (https://www.orpha.net/)


• OMIM: Phelan-McDermid syndrome; PHMDS (https://omim.org/)


• Phelan-McDermid Syndrome Foundation: Clinical resources and patient support (https://pmsf.org/)