About cheney syndrome

What is cheney syndrome?

Hajdu-Cheney syndrome (HCS) is a rare, heritable disorder of connective tissue; only about 50 cases have been reported in the medical literature. The breakdown of bone (osteolysis), especially the outermost bones of the fingers and toes (acroosteolysis), is a major characteristic of HCS.

In addition, patients with HCS frequently have skull deformities, short stature, joint laxity, reduction of bone mass (osteoporosis) and other signs. Most affected individuals have normal mental development but a small proportion show mild mental retardation.

Although the majority of cases are of unknown cause, the presence of multiple cases in one family suggests that autosomal dominant genetic transmission may be possible.



What are the symptoms for cheney syndrome?

The signs and symptoms of Hajdu-Cheney syndrome can vary greatly among affected individuals. The disorder is present at birth (congenital), but in some individuals the signs and symptoms may be more apparent during adolescence and adulthood.

Although researchers have been able to establish a clear syndrome with characteristic or “core” symptoms, much about the disorder is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genes influencing the disorder prevent physicians from developing a complete picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.

A characteristic finding is the breakdown of bone and tissue (osteolysis), particularly the outermost bones of the fingers and toes (acroosteolysis). This may be painless or can occur with inflammation, pain, Swelling and abnormal sensations like burning or tingling (paresthesia). In severe instances, the fingers and toes may be shortened and appear clubbed or rounded. Generally, the fingers are affected worse than the toes.

Some individuals also have a reduction of bone mass (osteoporosis), which predisposes individuals to fractures. Osteoporosis can be severe and fractures can be frequent. The bones of the spinal column, called the vertebrae, may be susceptible to compression fractures, in which the vertebrae collapse. This is extremely painful and can lead to spinal malformation. Some individuals may have abnormal sideways curvature of the spine (scoliosis) or an abnormal rounding of the spine (kyphosis) may occur. The long bones of the arms and legs can be misshapen or bowed. Because of these various skeletal problems, affected individuals may reach an adult height that is noticeably shorter than would otherwise be expected (short stature). Sometimes, these skeletal problems can become a significant impairment in daily life by late adolescent or early adulthood.

Individuals have distinctive facial features. Some features are noted during infancy or childhood, while others become more pronounced as affected individuals age. These features include eyes that are slightly farther apart than normal (mild hypertelorism); an abnormally wide space in between the upper and lower eyelids; a single, thick eyebrow over the eyes (synophrys); low-set ears, a high arched roof of the mouth (palate); a cleft palate; a Small jaw (micrognathia); flattening of the middle portion of the face; coarse hair; and a short neck. The range of motion of the neck may be limited.

There are also abnormalities of the skull including open sutures. An infant’s skull has seven bones and several joints called sutures. Sutures are made of tough, elastic fibrous tissue and separate the bones from one another. Sutures meet up (intersect) at two spots on the skull called fontanelles, which are better known as an infant’s “soft spots”. The seven bones of an infant’s skull usually fuse together until around age two or later. In affected adults, the occipital bone, which is located in the back of skull, may bulge outward, a condition called bathrocephaly.

Dental abnormalities are common including permanent teeth that get blocked as they try to emerge from the gums (impacted) and upper and lower teeth may not meet correctly when biting (malocclusion). There may be early loss of permanent teeth. The gums of affected individuals may be infected and swollen and bleed (periodontal disease).

Additional symptoms can include hearing loss, and joints that can be abnormally loose and flexible (joint hypermobility), and can be moved beyond their normal range. Various heart defects have been reported in some children. Abnormalities affecting the urinary tract can also occur. Some children experience protrusion of parts of the large intestine through an opening near the bellybutton (umbilical hernia).

Some affected individuals may have flattening of the base of the skull (platybasia). This may occur because the base of the skull is pushed upward because of basilar invagination. Basilar invagination occurs when the upper bones of the spinal column are located higher than normal, blocking the hole in the base of skull through which the spinal column passes. This blocks the flow of the fluid that surrounds the brain and spinal cord (cerebrospinal fluid). These conditions can cause excessive fluid accumulation and pressure within the brain (hydrocephalus), respiratory arrest, and sudden death.

A subset of affected individuals has polycystic kidney disease, which is the formation of cysts within the kidneys. This can cause Pain on both sides of the body between the last rib and hip (flank pain), blood in urine, and progressively poor function of the kidneys, which means that the kidneys will not be able to effectively remove waste products from the blood and excrete them in the urine.



What are the causes for cheney syndrome?

Hajdu-Cheney syndrome is associated with a change (mutation) in the NOTCH2 gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, absent, or have increased function. When there is increased function, this is called a gain-of-function mutation. In Hajdu-Cheney syndrome there is a gain of NOTCH2 protein function and increased activity of the protein. Depending upon the functions of the particular protein, this can affect many organ systems of the body.

The NOTCH2 gene produces a protein that is essential for the proper growth and development of the body. Because of the alterations to the NOTCH2 gene, the protein is stable and more effective. The exact manner that these gene changes result in the symptoms of Hajdu-Cheney syndrome is not fully understood.

The changes in the NOTCH2 gene that are associated with Hajdu-Cheney syndrome are inherited in an autosomal dominant manner but many sporadic cases occur. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.

In most individuals, physicians believe that the disorder occurs because of sporadic (de novo) genetic mutations that occur in the egg or sperm cell. In such situations, the disorder is not inherited from the parents and occurs randomly.



What are the treatments for cheney syndrome?

The treatment of Hajdu-Cheney syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, specialists who asses and treat disorders of the skeleton (orthopedists or orthopedic surgeons), specialists who assess and treat disorders of the heart (cardiologists), dental specialists, speech pathologists, specialists who asses and treat hearing problems (audiologists), and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment.

Genetic counseling is recommended for affected individuals and their families. Psychosocial support for the entire family is essential as well.

There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with Hajdu-Cheney syndrome.

Some individuals have been treated with medications that prevent bone resorption in order to treat osteoporosis. Normally, bone gradually breaks down (bone resorption) and then reforms, a process called bone turnover. It appears that excessive or accelerated bone turnover contributes to Hajdu-Cheney syndrome. The benefit of these medications has not been established.

Surgery may be necessary to treat various complications of Hajdu-Cheney syndrome including hydrocephalus, spinal cord abnormalities, cleft palate, and congenital heart defects. Hearing aids may be used to treat hearing loss.



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