Hajdu–Cheney syndrome

Hajdu–Cheney syndrome, also called acroosteolysis with osteoporosis and changes in skull and mandible, arthrodentoosteodysplasia and Cheney syndrome, is an extremely rare autosomal dominant congenital disorder of the connective tissue characterized by severe and excessive bone resorption leading to osteoporosis and a wide range of other possible symptoms. Approximately 70 cases have been reported worldwide.

Characteristics
Hajdu–Cheney syndrome causes short stature and extreme bone flexibility. The disorder can also cause mild cognitive delays, such as delayed speech acquisition. Fetuses with Hajdu–Cheney syndrome often will not be seen to unclench their hands on obstetrical ultrasound. They may also have low set ears and their eyes may be farther apart than on a usual child, called hypertelorism. Children's heads can have some deformities in their shape and size (plagiocephaly). Early tooth loss and bone deformities, such as serpentine tibias and fibulas, are also common in those affected.

Genetics
Hajdu–Cheney syndrome is inherited in an autosomal dominant pattern. This means that the defective gene responsible for the disorder is located on an autosome, and only one copy of the gene is sufficient to cause the disorder, when inherited from a parent who has the disorder.

Mutations within the last coding exon of NOTCH2 that remove the PEST domain and escape the nonsense-mediated mRNA decay have been shown to be the main cause of the Hajdu–Cheney syndrome.

Treatment
Since about 2002, some patients with this disorder have been offered drug therapy with bisphosphonates (a class of osteoporosis drugs) to treat problems with bone resorption associated with the bone breakdown and skeletal malformations that characterize this disorder.