How do I know if I have 22q13 deletion / Phelan-McDermid Syndrome?

TL;DR: Phelan-McDermid syndrome (22q13 deletion) is typically diagnosed through genetic testing after an individual presents with global developmental delay, absent or severely delayed speech, and neonatal hypotonia. If you suspect you or a loved one has this condition, you should request a chromosomal microarray analysis from a clinical geneticist to identify the specific deletion on the long arm of chromosome 22.

What are the early signs of Phelan-McDermid syndrome?

Phelan-McDermid syndrome is a rare genetic condition caused by the loss of the terminal end of chromosome 22 or a mutation in the SHANK3 gene. In infants and children, the most common clinical markers include significant hypotonia (low muscle tone), which often leads to delayed motor milestones like rolling over or walking. Parents frequently notice that their child has absent or severely delayed expressive speech, often accompanied by social-emotional challenges similar to those seen in autism spectrum disorder. Physical features, while variable, can include large, fleshy hands, dysplastic toenails, and a high pain threshold, which are hallmark indicators of 22q13 deletion.

How can I identify patterns for Phelan-McDermid syndrome?

Self-assessment for Phelan-McDermid syndrome involves looking for a constellation of symptoms rather than a single trait. Because this condition spans a wide spectrum of severity, symptoms can vary significantly. Key patterns to document include:

• Developmental milestones: Significant delays in speech and motor development that do not seem to be catching up with age-matched peers.


• Neurological markers: A history of neonatal hypotonia or the onset of seizures, which affect approximately 40% to 75% of individuals with Phelan-McDermid syndrome.


• Behavioral profile: Persistent social deficits, repetitive behaviors, or sleep disturbances that persist despite standard interventions.


• Physical traits: Distinctive facial features or subtle physical findings that a pediatrician might overlook during routine exams.

Which tests should I ask my doctor about?

If you are concerned about 22q13 deletion, it is vital to move beyond standard blood work. You must specifically request a chromosomal microarray (CMA). Standard karyotyping often misses small deletions; a microarray is the gold-standard test to detect the microdeletions associated with Phelan-McDermid syndrome. If the microarray is negative but clinical suspicion remains high, a clinical geneticist may recommend SHANK3 gene sequencing to rule out point mutations.

How do I advocate for a diagnosis?

When speaking to your physician, bring a documented list of developmental milestones and physical symptoms. Frame your request clearly: "Given the history of global developmental delay and hypotonia, I am concerned about a potential chromosomal microdeletion. Could we refer to a geneticist for a chromosomal microarray?" If your concerns are dismissed, do not hesitate to seek a second opinion from a specialist at a university-affiliated medical center or a genetics clinic. You are the expert on your or your child's health; persistence is often necessary when navigating rare conditions.

Next steps

• Consult with a clinical geneticist to discuss whether your symptoms align with the criteria for Phelan-McDermid syndrome.


• Join our community at DiseaseMaps.org, where 35 members currently share their experiences and insights regarding this diagnosis.


• Connect with the Phelan-McDermid Syndrome Foundation (PMSF) for disease-specific resources and support.


• Keep a detailed medical diary of all symptoms, including seizure activity, sleep patterns, and developmental progress, to share with your care team.

Medical disclaimer: This information is for educational purposes only and does not constitute medical advice; always consult with a qualified healthcare professional regarding any medical diagnosis or treatment.

References

• NIH Genetic and Rare Diseases (GARD) Information Center: Phelan-McDermid syndrome.


• Orphanet: 22q13.3 deletion syndrome (ORPHA:2610).


• OMIM (Online Mendelian Inheritance in Man): Phelan-McDermid syndrome (#606232).


• Phelan-McDermid Syndrome Foundation (PMSF): Clinical and family resources.