(OMIM phenotype number #102500)

Hajdu-Cheney syndrome is a very rare connective tissue disorder, caused by heterozygous mutation in the NOTCH2 gene. It has autosomal dominant inheritance or in some cases may occur due to spontaneous de novo mutation. The disease has been associated with mutations in exon 34 of NOTCH2 upstream the PEST domain, leading to the creation of a truncated and stable NOTCH2 protein with enhanced NOTCH2 signaling activity. Notch receptors, single-pass transmembrane proteins determining cell fate, have an important role in skeletal development and homeostasis. Clinical manifestations include: transverse band of acro-osteolysis involving the phalanges of both hands and feet, severe osteoporosis short stature, deformities involving skull, mandible, spine and other bones, and wormian bones, neurological symptoms, and cardiovascular defects and polycystic kidneys. The comlications, that may occur are: kyphoscoliosis, basilar invagination, and bone fractures due to bone softening.

Treatment is symptomatic. Bone antiresorptive and anabolic agents have been tried to treat the osteoporosis, but their benefit has not been established.


NOTCH2 gene, 1p12p11 (OMIM gene/locus number #600275).


Short stature, coarse and dysmorphic facies, bowing of the long bones, vertebral anomalies Facial features include hypertelorism, bushy eyebrows, micrognathia, small mouth with dental anomalies, low-set ears, and short neck. Progressive focal bone destruction, including acroosteolysis and generalized osteoporosis. Additional and variable features include hearing loss, renal cysts, and cardiovascular anomalies.


Fig. 43-year-old female patient with Hajdu-Cheney syndrome. Frontal radiograph of right hand (A) shows transverse band of osteolysis involving distal phalanx of second and third finger and middle phalanx of fifth finger. There is near complete osteolysis of distal phalanx of thumb. Marginal erosion is noted at distal interphalangeal joint of fourth finger. Radiograph of left hand (B) shows transverse osteolysis involving distal phalanx of thumb, second and third finger and middle phalanx of fifth finger. The fourth finger is spared. The soft tissues around the tips of terminal phalanges of both hands appear normal. No periarticular or any soft tissue calcification is seen in both hands.

Reproduced from J Radiol Case Rep. 2014 Sep 30;8(9):1-8 under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License.


  1. Palav S, Vernekar J, Pereira S, et al. Hajdu-Cheney syndrome: a case report with review of literature. J Radiol Case Rep. 2014 Sep 30;8(9):1-8.
  2. Canalis E, Zanotti S. Hajdu-Cheney syndrome: a review. Orphanet J Rare Dis. 2014 Dec 10;9:200.
  3. Zanotti S, Canalis E. Notch signaling in skeletal health and disease. Eur J Endocrinol. 2013 May 8;168(6):R95-103.
  4. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  5. http://www.omim.org