Emery-Dreifuss Muscular Dystr... Health Article

Autosomal dominant form

In some families, Emery-Dreifuss muscular dystrophy may be inherited in an autosomal dominant pattern. Autosomal dominant EDMD is known as Emery-Dreifuss muscular dystrophy 2 (EDMD2), Hauptmann-Thannhauser muscular dystrophy, and Scapuloilioperoneal atrophy with cardiopathy. Autosomal dominant disorders affect both sexes equally. In autosomal dominant conditions a person, male or female, requires only one faulty gene to produce disease. There are no unaffected carriers of EDMD2. In families with EDMD2, both males and females can be affected and father to son inheritance of the disease can occur. Every child of a person affected with EDMD2 has a 50% chance of inheriting the disease.

In families with EDMD2, affected members exhibit a later onset of the same symptoms as someone affected with X-linked EDMD. Symptoms begin between the ages of 17 and 42. EDMD2 and X-linked EDMD are caused by changes in different genes on different chromosomes.

Muscle biopsy of people with EDMD2 are found to have normal emerin levels. In families with EDMD2, the disease is caused by changes, or mutations, in a gene known as Lamin A/C, or LMNA. Lamin A/C is located in a specific area on the long arm of chromosome 1 known as 1q21.2.

Lamin A/C codes for two proteins, lamins A and C. Like emerin, these lamins are associated with the nuclear membrane. People with autosomal dominant EDMD2 have normal levels of emerin and low levels of these lamin proteins. Emerin and these lamins form an important protein complex in a cell's nuclear membrane. The exact role of this complex is unclear. Scientists theorize that this important complex of proteins stabilizes the nuclear membrane and plays a role in regeneration of muscle fibers.

Autosomal recessive form

As of early 2001 a single case of autosomal recessively inherited EDMD has been documented. EDMD of autosomal recessive inheritance has been named Emery-Dreifuss muscular dystrophy 3 (EDMD3). For someone to be affected with an autosomal recessive disease they must inherit two copies of a disease-causing gene, one from each parent. A parent who has only one gene associated with autosomal recessive EDMD is not affected by the disease and is known as a carrier of the disease. Two carriers of autosomal recessive EDMD have a 25% chance to have a child affected with the disorder in each pregnancy.

Like EDMD2, EDMD3 is caused by mutations in the Lamin A/C gene located on the long arm of chromosome 1 at an area designated as 1q21.2. The single known mutation associated with EDMD3 has not been found to also lead to EDMD2.

The single known patient with autosomal recessively inherited EDMD (EDMD3) displayed symptoms similar to those of X-linked and autosomal dominant EDMD without any heart involvement. He had difficulties when he started walking at 14 months of age. At five years of age, his contractures were so severe that he could not stand. At age 40, he was confined to a wheelchair and exhibited severe widespread muscle wasting. He displayed normal intelligence and did not have any heart problems. His carrier parents had no heart, skeletal, or muscle abnormalities.

Demographics

X-linked EDMD is estimated to occur in one in 100,000 births. EDMD2 and EDMD3 are far less common. Only one case of EDMD3 has been documented.

Only males exhibit full symptoms of X-linked EDMD. EDMD2 and EDMD3 may occur in males and females. X-linked EDMD and EDMD2 have been documented in many countries. There does not appear to be a single founder of these diseases, as many families have distinctly different backgrounds and different diseasecausing mutations.

Signs and symptoms

Emery-Dreifuss muscular dystrophy is recognized by a classic triad of symptoms: contractures at a young age, progressive muscle weakness and degeneration involving the upper arms and lower legs, and cardiac (heart) muscle disease.