Rare Genetic Diseases: Camurati-Engelmann Disease
Camurati-Engelmann disease is a rare genetic disorder occurring in only 300 individuals worldwide. It is characterized as a skeletal condition with abnormally thick bones (hyperostosis) in the arms, legs, and skull.
The thick limb bones can lead to bone pain and muscle weakness in the arms and legs. The pain may worsen with stress, activity, or cold weather. The individuals affected by Camurati-Engelmann disease suffer from joint deformities (contractures), flat feet (pes planus) as well as swelling and redness (erythema) of the limbs, and abnormal curvature of the spine. The age at which the first symptom presents varies among the individuals.
The characteristic facial features are caused by the abnormally thick skull and include an unusually large head (macrocephaly), lower jaw (mandible) as well as prominent forehead (frontal blossing), and bulging eyes with shallow eye sockets (ocular proptosis). ¼ of the patients have neurological problems, such as headaches, hearing loss, and impaired vision, caused by the thickened skull which increases the pressure on the brain or compresses the spinal cord.
The alteration responsible for the disorder is located in the TGFB1 gene. In a healthy individual, the gene produces a protein called transforming growth factor beta-1. TGFbeta1 protein triggers chemical signals that regulate various cell activities. Among these are growth and division (proliferation) of the cells, the maturation (differentiation) of the cells to carry out a specific function, and controlled cell death (apoptosis). The protein is particularly abundant in the skeleton, where it regulates bone and cartilage formation.
The mutation results in overly active TGFbeta1, which leads to increased signaling culminating in more bone formation. Camurati-Englemann disease is inherited in an autosomal dominant pattern which means that one copy of the altered gene in each cell is sufficient to cause the disorder. Some individuals who have the altered gene never develop the condition. This situation is known as reduced penetrance.
The Camurati-Engelmann disease is somewhat treatable with glucocorticoids, a medicine that improves bone strength and treats multiple side effects.
