Hajdu Cheney syndrome ... (Hajdu-Cheney syndrome) - Gen NOTCH2.

Hajdu Cheney syndrome is a rare disorder that can affect many parts of the body, especially bones. Signs and symptoms of the disease may include acro-osteolysis, osteoporosis, compression fractures of the vertebrae, scoliosis or kyphosis. Affected individuals also have abnormalities of the skull bones, including the bones of the face. Often the shape of the skull is described as dolichoceplhalic. In addition, the bone in the back of the skull bulges outward, causing a protrusion called prominent occiput. For its part, the distinctive facial features include widely spaced eyes and tilted down, low - set ears, midface hypoplasia, a long philtrum and cleft palate or ogival. Other characteristics of Hajdu Cheney syndrome found in some affected individuals include joint abnormalities and hypermobility, dental problems, hearing loss, deep, gravelly voice, excessive body hair, recurrent childhood infections, heart defects and abnormalities such as polycystic kidney kidneys. Some people with this disease have developmental delay in childhood, but delays are usually mild.

The most serious complications of Hajdu Cheney syndrome, occurring in about half of all people affected are anomalies known as platybasia and basilar invagination. These abnormalities can lead to serious neurological problems including headaches, abnormal vision and balance, hydrocephalus, abnormal breathing and sudden death. Signs and symptoms of Hajdu Cheney syndrome vary greatly among affected individuals, even among members of the same family. Many of the features of the disease, acro-osteolysis and as some of the characteristic facial features are not present at birth but manifested in childhood or later. The risk of intussusception basilar platybasia and also increases over time.

The features of Hajdu Cheney syndrome overlap significantly with a condition called serpentine fibula syndrome, or polycystic kidney disease (SFPKS). Although used various alterations be considered, the two conditions are associated with mutations in the same gene. Based on these similarities, many researchers now consider SFPKS syndrome and Hajdu-Cheney Syndrome are variants of the same disease.

This process is due to mutations in the gene NOTCH2, located on the short arm of chromosome 1 (1p13-p11). This gene encodes a protein called Notch2, a member of the family of Notch receptors. The binding of a ligand to Notch2 receptor transmits signals that are important for development and normal function of many tissues throughout the body, both before and after birth. In particular, the Notch2 signaling is important for the development of cells destined to form part of the heart, liver, kidneys, teeth, bones and other structures in a growing embryo. After birth, the Notch2 signaling is involved in immune system function, tissue repair and bone remodeling.

They are associating several mutations in the gene with NOTCH2 Hajdu-Cheney Syndrome. The identified mutations are present in exon 34. These mutations lead to an abbreviated version of Notch2 receptor in the domain PEST missing. Without this domain, the receiver can not divide normally, and Notch2 signaling within the cell continues after stopping due. Because NOTCH2 genetic mutations related Hajdu-Cheney Syndrome cause abnormal increase of Notch2 signaling, are described as "gain of function mutations." Although it is unclear how excess signaling Notch2 is related to the various features of Hajdu Cheney syndrome is likely to skeletal disease characteristics, including acro-osteolysis, osteoporosis and distinctive facial features, they are probably due to the development and abnormal bone remodeling. Excess signaling through the hyper Notch2 receptor can increase the removal of aged bone, reducing the formation of new bone, or both. It is less clear how the hyperactive receptor contributes to the other signs and symptoms of this disease.

The Hajdu-Cheney Syndrome is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell NOTCH2 is sufficient to express the disease. Most cases are due to new mutations in the gene and occur in people with no history of disease in your family. Less often, an affected person inherits the mutation from an affected parent.

Tests in IVAMI: in IVAMI perform detection of mutations associated with Hajdu Cheney syndrome by complete PCR amplification of the exons of the gene NOTCH2 and subsequent sequencing. The most frequent mutation is located in exon 34, so we offer the possibility of starting the test with this exon and, if found, would not have to continue studying the other exons, thus reducing time implementation and cost.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).