About camurati-engelmann disease

What is camurati-engelmann disease?

Camurati-Engelmann disease is a rare genetic disorder characterized by progressive widening and malformation of the shafts of the long bones (diaphyseal dysplasia). Major symptoms may include bone pain, particularly in the legs; skeletal abnormalities; and/or weakness and underdevelopment (hypoplasia) of various muscles. Pain and weakness of the leg muscles may result in an unusual "waddling" walk (gait). Camurati-Engelmann disease is inherited as an autosomal dominant trait.

What are the symptoms for camurati-engelmann disease?

The first signs and symptoms of CED are usually limb pain, a waddling gait, muscle weakness, and extreme tiredness. If the bones at the base of the skull are affected, the individual may experience headaches, hearing loss, vision problems, vertigo, tinnitus, and even facial paralysis. Additional musculoskeletal features include scoliosis, joint contractures, knock knees, and flat feet. The individual may also present with abnormally long limbs in proportion to the height of their body, a decrease in muscle mass and body fat, visible prominence of the long bones in the legs, and rarely delayed puberty. While the first signs and symptoms can appear at varying ages, most appear during childhood or adolescence.

The signs and symptoms of CED can be extremely variable even among affected family members. Some individuals with a TGFB1 mutation do not develop signs or symptoms of the disease or evidence of increased bone density on X-ray examination (i.e., reduced penetrance).

What are the causes for camurati-engelmann disease?

CED is caused by mutations in TGFB1 which encodes transforming growth factor beta-1 protein. This protein helps control the growth and proliferation of cells, the process by which the cells mature and begin to specify (differentiate), cell movement, and cell directed self-destruction (apoptosis). The specific protein plays a huge role during prenatal development in the formation of blood vessels, the regulation of muscle tissue and body fat development, wound healing, and immune system function. The protein is most abundant in skeletal tissue and the extracellular matrix that provides structural support and nutrients to the surrounding cells.

Normally, TGFB1 is inactive until a chemical signal is sent to turn it on. TGFB1 mutations that cause CED result in the gene being always turned on and active. This leads to increased bone density and decreased fat and muscle tissue, contributing to the symptoms listed above. Most individuals with CED have a TGFB1 mutation identified on molecular genetic testing, but some affected individuals do not.

CED is inherited as an autosomal dominant condition. This occurs when only a single copy of the mutated gene is needed to cause a specific disorder. The altered gene can be inherited from either parent, or can be a new mutation in the affected individual. The risk of transmitting the disease to the offspring of an affected parent is 50%, and is the same for males and females. Rarely, the disease can come from a spontaneous genetic mutation in the egg or sperm cell. In these people, the disease isn’t inherited from the one of the parents, but the individual can still pass it to their offspring.

What are the treatments for camurati-engelmann disease?

Treatment for CED consists of management of symptoms. To manage the pain caused by the thickening of the bones, individuals may be treated with corticosteroids, and non-steroidal anti-inflammatory drugs (NSAIDs). Corticosteroids have shown benefits in affected individuals. Although they are helpful to improve walking, the major side effects of taking corticosteroids long term may outweigh the benefits of the drugs. Some of these side effects include high blood sugar, increased risk of infections, and suppressed adrenal hormone production. Losartan has been reported to reduce limb pain and increase muscle strength in some individuals. No formal studies have been completed on the efficacy of losartan and data are limited on the long term effects and benefits of this drug.

For those with hearing problems caused by the thickening of the bones of the base of the skull, decompression surgery in which a small piece of the base of the skull is removed has been done in some individuals with mixed results. This procedure can result in an increased risk of complications as well as the possibility for bone to re-grow after the surgery.

What are the risk factors for camurati-engelmann disease?

CED is inherited as an autosomal dominant condition. This occurs when only a single copy of the mutated gene is needed to cause a specific disorder. The altered gene can be inherited from either parent, or can be a new mutation in the affected individual. The risk of transmitting the disease to the offspring of an affected parent is 50%, and is the same for males and females. Rarely, the disease can come from a spontaneous genetic mutation in the egg or sperm cell. In these people, the disease isn’t inherited from the one of the parents, but the individual can still pass it to their offspring.

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