What is Hajdu-Cheney Syndrome

Hajdu-Cheney syndrome is an extremely rare genetic connective tissue disorder characterized by progressive bone loss (acro-osteolysis), distinct craniofacial features, and skeletal abnormalities. It is caused by specific mutations in the NOTCH2 gene, which disrupt essential signaling pathways involved in bone remodeling and development.

What are the primary symptoms of Hajdu-Cheney syndrome?

The clinical presentation of Hajdu-Cheney syndrome is multisystemic. The most diagnostic feature is acro-osteolysis, which is the progressive resorption (dissolving) of the terminal bones in the fingers and toes. Other common clinical manifestations include:

• Skeletal abnormalities: Severe osteoporosis, early-onset fractures, and delayed closure of the fontanelle.


• Craniofacial features: A distinct appearance including low-set ears, a short neck, and dental anomalies like premature tooth loss or hyperdontia.


• Neurological/Systemic: Potential for basilar invagination (where the base of the skull pushes into the spinal canal) and cardiovascular issues.

What causes Hajdu-Cheney syndrome?

Hajdu-Cheney syndrome is caused by gain-of-function mutations in the NOTCH2 gene. Unlike many genetic conditions that are recessive, this syndrome follows an autosomal dominant inheritance pattern, meaning a single copy of the mutated gene is sufficient to cause the condition. In many cases, it occurs as a "de novo" mutation, meaning it is not inherited from either parent.

How rare is this condition?

Hajdu-Cheney syndrome is exceptionally rare, with fewer than 100 cases reported in medical literature worldwide. Because it is so uncommon, it is often underdiagnosed or misdiagnosed as other skeletal dysplasias. Currently, 5 people within the DiseaseMaps.org community have identified themselves as living with Hajdu-Cheney syndrome, providing a vital space for peer support.

How is it differentiated from other conditions?

What distinguishes Hajdu-Cheney syndrome from other acro-osteolysis syndromes is the specific combination of early-onset osteoporosis and the unique craniofacial profile. Genetic testing is the gold standard for confirmation, as clinical symptoms can overlap with conditions like pycnodysostosis or Torg-Winchester syndrome.

Next steps

• Consult with a clinical geneticist to confirm a diagnosis through NOTCH2 sequencing.


• Schedule a baseline skeletal survey and neurological evaluation to monitor for basilar invagination.


• Connect with others on DiseaseMaps.org to share experiences and coping strategies for this rare diagnosis.

Medical disclaimer: This information is for educational purposes and should not replace professional medical advice, diagnosis, or treatment.

References

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


• Orphanet: Rare disease database entry for Hajdu-Cheney syndrome.


• OMIM (Online Mendelian Inheritance in Man): Entry #102500.


• National Library of Medicine (PubMed): Clinical reviews on NOTCH2-related disorders.