Hajdu-Cheney syndrome was first described as cranioskeletal dysplasia 1 in 1948. It is a very rare connective tissue disorder with only 50 cases reported in the literature 2.
It is mostly diagnosed in adulthood or adolescence with the presence of a positive family history. There has been no link between severity of disease and age of diagnosis 3. Clinical features include:
- short stature; premature loss of dentition; short webbed neck
- pseudoclubbing; shortening of digits; pain in digits
- optical atrophy; optic disc oedema
- hearing loss (conductive or sensorineural)
- frontal and occipital headaches (due to basilar invagination)
- craniofacial features: frontal bossing, widely spaced eyes, micrognathia, long philtrum, flat nasal bridge, coarse hair, low set ears and a low hairline
Diagnosis involves genetic testing searching for the truncating mutation in the terminal exon of NOTCH2.4
- congenital heart disease (VSD, ASD, PDA, Mitral regurgitation)
- polycystic kidney disease
- recurrent respiratory tract infections
Hands and feet
- transverse band of osteolysis in distal phalanges is characteristic.
- distal to proximal osteolysis is also seen
- bathrocephaly (bulging of squamous occipital bone)
- delayed closure of sutures
- thickening of mastoids
- aplasia of the frontal sinus
- J-shaped enlarged sella
- platybasia with or without basilar invagination
- hypoplastic maxilla
- malalignment of teeth
- wide mandibular angle
Treatment and prognosis
Management is symptomatic and involves regular follow-up. Prevention of osteoporosis, vitamin D and bisphosphonates may also have a role 6.
These involve other causes of acro-osteolysis and can be differentiated radiologically 5. Amongst others, they include the following:
- 1. Hajdu N, Kauntze R. Cranio-Skeletal Dysplasia. British Journal of Radiology. 1948 Jan 1;21(241):42-8.
- 2. Simpson MA, Irving MD, Asilmaz E et-al. Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. Nat. Genet. 2011;43 (4): 303-5. doi:10.1038/ng.779 - Pubmed citation
- 3. Palav S et al. Hajdu – Cheney Syndrome: A case report with review of literature. Journal of Radiology Case Reports. 2014 Sep 8(9):1-8.
- 4. Zhao W, Petit E, Gafni RI et-al. Mutations in NOTCH2 in patients with Hajdu-Cheney syndrome. Osteoporos Int. 2013;24 (8): 2275-81. doi:10.1007/s00198-013-2298-5 - Free text at pubmed - Pubmed citation
- 5. Stathopoulos IP, Trovas G, Lampropoulou-Adamidou K et-al. Severe osteoporosis and mutation in NOTCH2 gene in a woman with Hajdu-Cheney syndrome. Bone. 2013;52 (1): 366-71. doi:10.1016/j.bone.2012.10.027 - Pubmed citation
- 6. O'Reilly MA, Shaw DG. Hajdu-Cheney syndrome. Ann. Rheum. Dis. 1994;53 (4): 276-9. Free text at pubmed - Pubmed citation