Emery-Dreifuss muscular dystrophy

Emery-Dreifuss muscular dystrophy (EDMD) is a progressive muscle-wasting disorder defined by early contractures of the Achilles tendon, spine, and elbows. EDMD is also distinctive for its association with defects of the cardiac conduction system that can result in sudden death. It can be inherited in an X-linked, autosomal dominant, or autosomal recessive fashion and is caused by mutations in proteins of the nuclear membrane. Mutations in the EMD gene, which encodes emerin, a transmembrane protein found at the inner nuclear membrane, are responsible for X-linked EDMD. The most common etiology of autosomal dominant EDMD is an LMNA gene mutation; LMNA encodes the intermediate filament protein lamins A and C, which constitute the major scaffolding protein of the inner nuclear membrane. Murine models of LMNA gene mutations have helped to identify different mechanisms of disease. Loss of LMNA function leads to nuclear fragility as well as other defects, such as abnormal nuclear function. Additional genes encoding nuclear membrane proteins such as SYNE1 and SYNE2 have also been implicated in EDMD, and in some cases their importance for cardiac and muscle function has been supported by animal modeling.