Which are the symptoms of 22q13 deletion / Phelan-McDermid Syndrome?

TL;DR: Phelan-McDermid syndrome (22q13 deletion) is primarily characterized by global developmental delay, absent or severely delayed speech, and neonatal hypotonia. Symptoms vary widely based on the size and location of the genetic deletion, but most individuals experience lifelong challenges with communication, sensory processing, and intellectual development.

What are the most common symptoms of Phelan-McDermid syndrome?

The clinical presentation of Phelan-McDermid syndrome is highly variable, yet certain features appear consistently across the population. Because this condition is caused by a deletion or mutation in the SHANK3 gene, it often manifests as a neurodevelopmental disorder. Common clinical observations include:

• Absent or severely delayed speech: Most individuals with Phelan-McDermid syndrome have limited or no functional verbal communication.


• Hypotonia: Low muscle tone is frequently present from birth, often leading to delayed motor milestones such as sitting, crawling, and walking.


• Distinctive facial features: While subtle, these may include long eyelashes, a long head shape (dolichocephaly), fleshy hands, and deep-set eyes.


• Intellectual disability: Most patients exhibit a range of cognitive impairments, typically falling into the moderate to profound range.


• Autism Spectrum Disorder (ASD): A significant majority of individuals with Phelan-McDermid syndrome meet the clinical criteria for autism.

How does 22q13 deletion syndrome impact daily quality of life?

Daily life for families affected by Phelan-McDermid syndrome is often shaped by sensory processing differences and gastrointestinal issues. Many individuals experience a high pain threshold, which can make it difficult for caregivers to identify injury or illness. Furthermore, sleep disturbances are reported in a large percentage of patients, which can significantly impact the well-being of the entire family. Seizure disorders affect approximately 25% to 40% of individuals, requiring careful monitoring and management by a neurologist.

How do symptoms change or progress over time?

The trajectory of Phelan-McDermid syndrome is not static. While early life is often dominated by hypotonia and feeding difficulties, adolescence may bring new challenges. Some individuals may experience a regression in skills, particularly in communication or social interaction. Conversely, many continue to make gradual developmental gains throughout adulthood with consistent support. It is important to note that the 35 members of our DiseaseMaps.org community highlight that personalized, early intervention therapies are crucial for maximizing long-term functional independence.

When should families seek immediate medical attention?

Given the potential for comorbidities, families should seek urgent medical evaluation if they observe sudden changes in behavior, unexplained lethargy, or signs of acute gastrointestinal distress, as these can sometimes mask underlying issues like bowel obstructions or status epilepticus. Because individuals with Phelan-McDermid syndrome may not be able to verbalize pain, any sudden change in irritability or physical function should be taken seriously by a medical professional.

Next steps

• Consult with a clinical geneticist to confirm the specific size and location of the 22q13 deletion.


• Schedule regular evaluations with a neurologist, especially if there are concerns regarding seizures or sleep disorders.


• Engage with speech and occupational therapists who specialize in neurodevelopmental disorders.


• Join the Phelan-McDermid Syndrome community on DiseaseMaps.org to connect with other families and share experiences regarding symptom management.

Medical disclaimer: This content is for informational 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 Genetic and Rare Diseases Information Center (GARD): Phelan-McDermid syndrome.


• Orphanet: 22q13.3 deletion syndrome.


• OMIM (Online Mendelian Inheritance in Man): SHANK3 gene and associated deletions.


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