Is 22q13 deletion / Phelan-McDermid Syndrome hereditary?

TL;DR: Phelan-McDermid syndrome (22q13 deletion) is a genetic condition, but in the vast majority of cases, it is not hereditary; it arises from a de novo (spontaneous) genetic change occurring during the formation of reproductive cells or early embryonic development. While parents of an affected child are very rarely carriers, clinical genetic testing is essential for every family to confirm the specific chromosomal change and determine recurrence risks for future pregnancies.

Is Phelan-McDermid syndrome hereditary?

To understand Phelan-McDermid syndrome, it is important to distinguish between "genetic" and "hereditary." The condition is definitively genetic because it is caused by a deletion or mutation of the SHANK3 gene located on the terminal end of chromosome 22. However, it is not typically "hereditary" in the traditional sense, meaning it is rarely passed down from a parent to a child. In approximately 80% to 90% of cases, 22q13 deletion / Phelan-McDermid syndrome occurs as a de novo mutation, meaning the genetic change is brand new to the individual and was not inherited from either parent.

What is the risk of recurrence for parents?

For most families, the chance of having another child with Phelan-McDermid syndrome is very low, generally estimated at less than 1%. However, in a small percentage of cases, a parent may carry a balanced chromosomal rearrangement (such as a translocation) that involves the 22q13 region. If a parent carries such a rearrangement, the risk of recurrence in future pregnancies can be significantly higher. Because of this, it is standard practice to perform parental blood tests (karyotype or chromosomal microarray) to rule out a balanced translocation in the parents.

How is this condition diagnosed through genetic testing?

The diagnosis of 22q13 deletion / Phelan-McDermid syndrome is confirmed through specialized genetic testing. Because the deletion can be very small, older techniques like standard karyotyping may miss it. Current clinical recommendations include:

• Chromosomal Microarray (CMA): The gold standard for detecting the loss of genetic material at the 22q13.3 locus.


• Whole Exome or Genome Sequencing: Used if a microarray is negative but clinical suspicion remains high, as some cases are caused by point mutations within the SHANK3 gene rather than a large deletion.


• Parental Testing: Essential for all families to determine if the deletion is de novo or inherited from a parent with a balanced translocation.

What is the role of genetic counseling for families?

Genetic counseling is a vital step for any family navigating a diagnosis of 22q13 deletion / Phelan-McDermid syndrome. A genetic counselor helps families interpret complex test results, explains the implications for siblings and extended family members, and provides accurate information regarding reproductive options. For those within our community, including the 35 members on DiseaseMaps.org who have shared their experiences, counseling provides a space to address fears about recurrence and discuss prenatal diagnostic options, such as amniocentesis or chorionic villus sampling (CVS), for future pregnancies.

Next steps

• Consult with a board-certified clinical geneticist to review your family’s specific genetic reports.


• Request parental chromosomal microarray testing to confirm if the 22q13 deletion / Phelan-McDermid syndrome is de novo.


• Connect with the Phelan-McDermid Syndrome Foundation for resources, clinical trial information, and support.


• Engage with the community at DiseaseMaps.org to connect with other families navigating the same diagnosis.

Medical Disclaimer: This information is for educational purposes only and should not replace professional medical advice, diagnosis, or treatment from a qualified healthcare provider.

References

• NIH GARD: Phelan-McDermid syndrome overview and genetic causes.


• Orphanet: Clinical data and diagnostic guidelines for 22q13.3 deletion syndrome.


• OMIM (Online Mendelian Inheritance in Man): Detailed molecular data on the SHANK3 gene and 22q13.3 deletion.


• Phelan-McDermid Syndrome Foundation: Expert-reviewed resources for families and clinicians.