Hajdu-Cheney syndrome
Encyclopedia
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.
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.
s (a class of osteoporosis drugs) to treat problems with bone resorption associated with the bone breakdown and skeletal malformations that characterize this disorder.
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
dominant congenital disorder
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
of the connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
characterized by severe and excessive bone resorption
Bone resorption
Bone resorption is the process by which osteoclasts break down bone and release the minerals, resulting in a transfer of calcium from bone fluid to the blood....
leading to osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
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
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
, 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
NOTCH2
Neurogenic locus notch homolog protein 2 also known as notch 2 is a protein that in humans is encoded by the NOTCH2 gene.NOTCH2 is associated with Alagille syndrome and Hajdu–Cheney syndrome.- Function :Notch 2 a member of the notch family...
that remove the PEST
PEST sequence
A PEST sequence is a peptide sequence which is rich in proline , glutamic acid , serine , and threonine . This sequence is associated with proteins that have a short intracellular half-life; hence, it is hypothesized that the PEST sequence acts as a signal peptide for protein degradation.The...
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 bisphosphonateBisphosphonate
Bisphosphonates are a class of drugs that prevent the loss of bone mass, used to treat osteoporosis and similar diseases...
s (a class of osteoporosis drugs) to treat problems with bone resorption associated with the bone breakdown and skeletal malformations that characterize this disorder.
External links
- Acroosteolysis dominant type at OrphanetOrphanetOrphanet is a European website providing information about orphan drugs and rare diseases. It contains content both for physicians and for patients. Its administrative office is in Paris. The organisation also publishes the open-access online journal Orphanet Journal of Rare Diseases.-External...
- Information on Hajdu–Cheney syndrome from a parent