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Review
. 2016 Aug;14(4):126-31.
doi: 10.1007/s11914-016-0311-6.

Hajdu-Cheney Syndrome, a Disease Associated with NOTCH2 Mutations

Ernesto Canalis  1 , Stefano Zanotti  2
Affiliations
Review

Hajdu-Cheney Syndrome, a Disease Associated with NOTCH2 Mutations

Ernesto Canalis et al. Curr Osteoporos Rep. 2016 Aug.

Abstract

Notch plays an important function in skeletal homeostasis, osteoblastogenesis, and osteoclastogenesis. Hajdu-Cheney syndrome (HCS) is a rare disease associated with mutations in NOTCH2 leading to the translation of a truncated NOTCH2 stable protein. As a consequence, a gain-of-NOTCH2 function is manifested. HCS is inherited as an autosomal dominant disease although sporadic cases exist. HCS is characterized by craniofacial developmental defects, including platybasia and wormian bones, osteoporosis with fractures, and acro-osteolysis. Subjects may suffer severe neurological complications, and HCS presents with cardiovascular defects and polycystic kidneys. An experimental mouse model harboring a HCSNotch2 mutation exhibits osteopenia secondary to enhanced bone resorption suggesting this as a possible mechanism for the skeletal disease. If the same mechanisms were operational in humans, anti-resorptive therapy could correct the bone loss, but not necessarily the acro-osteolysis. In conclusion, HCS is a devastating disease associated with a gain-of-NOTCH2 function resulting in diverse clinical manifestations.

Keywords: Acro-osteolysis; Bone remodeling; Fractures; Hes; Notch.

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Conflict of interest statement

Conflict of Interest

Ernesto Canalis and Stefano Zanotti declare that they have no conflict of interest.

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