Is Hajdu-Cheney Syndrome hereditary?

Hajdu-Cheney Syndrome is a rare genetic disorder caused by mutations in the NOTCH2 gene. It follows an autosomal dominant inheritance pattern, meaning a single copy of the mutated gene is sufficient to cause the condition, though many cases occur as sporadic, de novo mutations in individuals with no family history.

Is Hajdu-Cheney Syndrome hereditary?

Hajdu-Cheney Syndrome is considered a genetic disorder because it is caused by a specific mutation in the NOTCH2 gene. While it can be hereditary—meaning passed from an affected parent to a child—it is frequently the result of a de novo (spontaneous) mutation. In cases where a parent is affected, there is a 50% chance of passing the NOTCH2 mutation to each offspring, consistent with autosomal dominant inheritance.

How is a diagnosis of Hajdu-Cheney Syndrome confirmed?

Genetic testing is the gold standard for confirming a diagnosis of Hajdu-Cheney Syndrome. Because the clinical presentation can overlap with other skeletal dysplasias, molecular testing is essential. If you or a family member suspects Hajdu-Cheney Syndrome, the following steps are typically involved:

• Clinical Evaluation: Assessment of characteristic features like acro-osteolysis (bone resorption in the fingers/toes) and craniofacial changes.


• Molecular Genetic Testing: Targeted sequencing or gene panel testing to identify pathogenic variants in the NOTCH2 gene.


• Genetic Counseling: Reviewing family history to determine if the mutation is inherited or a new occurrence.

What role does genetic counseling play for families?

Genetic counseling is vital for families managing Hajdu-Cheney Syndrome. Counselors help interpret complex genetic results and discuss reproductive options, such as prenatal diagnosis or preimplantation genetic testing (PGT) for future pregnancies. Because Hajdu-Cheney Syndrome is rare, counseling provides a space to address concerns regarding the 50% recurrence risk for affected parents and the implications for extended family members.

Next steps

• Consult with a clinical geneticist to discuss molecular testing for Hajdu-Cheney Syndrome.


• Connect with the Hajdu-Cheney Syndrome community on DiseaseMaps.org to share experiences with the 5 other members currently registered.


• Schedule a session with a genetic counselor to discuss family planning and inheritance risks.

Medical disclaimer: This information is for educational purposes only and does not replace professional medical advice, diagnosis, or treatment; always seek the advice of your physician.

References

• NIH Genetic and Rare Diseases Information Center (GARD): Hajdu-Cheney Syndrome


• OMIM (Online Mendelian Inheritance in Man): NOTCH2 gene and Hajdu-Cheney Syndrome (#102500)


• Orphanet: Hajdu-Cheney Syndrome (ORPHA:391)