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.
The symptoms associated with Camurati-Engelmann disease vary greatly from case to case even among affected family members. Some affected individuals may exhibit few or no symptoms of the disorder (asymptomatic), others may exhibit significant disability.
The age of onset of Camurati-Engelmann disease also varies greatly from case to case. Most cases become apparent during early childhood. However, symptoms may become apparent as early as three months of age or as late as the sixth decade of life.
Camurati-Engelmann disease is characterized by bone pain, especially in the long bones of the upper legs (femurs). In many cases, muscle weakness and pain in the legs may result in an unusual “waddling” walk (gait). In some cases, bone pain is even severe enough to prevent walking. In about half of the affected individuals, hardening (sclerosis) of the bones at the base of the skull occurs, possibly leading to vision and hearing impairment and facial paralysis.
In some cases, fatigue, headaches, poor appetite, exophthalmos (abnormal protrusion of the eyeball), reduced subcutaneous fat, and/or swelling of the lower legs may also be associated with Camurati-Engelmann disease. In rare cases, the liver and spleen may be enlarged (hepatosplenomegaly).
Camurati-Engelmann disease is inherited as an autosomal dominant trait. Some cases of Camurati-Engelmann disease occur without a previous family history of the disorder, resulting instead from a spontaneous genetic change (i.e., new mutation). The inheritance of this mutation is autosomal dominant.
Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed “dominating” the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child. The risk is the same for each pregnancy.
Investigators have determined that most cases of Camurati-Engelmann disease are caused by disruption or changes (mutations) in the transforming growth factor-beta-1 (TGFB1) gene.
The TGFB1 gene is located on the long arm (q) of chromosome 19 (19q13.1). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q.” Chromosomes are further subdivided into bands that are numbered. For example, “chromosome 19q13.1” refers to band 13.1 on the long arm of chromosome 19.
Camurati-Engelmann disease is a rare disorder affecting males and females in equal numbers. The disorder usually becomes apparent before 30 years of age; in many cases, onset is before 10 years of age. More than 100 cases have been reported in the medical literature.
Treatment of Camurati-Engelmann disease usually involves the use of low-doses of steroid drugs such as cortisone, prednisone or deflazacort to relieve the symptoms. Surgical correction (osteotomy) of lower limb abnormalities has been performed in some cases. Eye surgery to decompress the optic nerves is usually ineffective and is usually not recommended.
Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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