This is a group of disorders that encompasses at least six different genetic types, the most common probably being an X-linked muscular dystrophy characterized by the special feature of muscle contractures. That process is relatively benign in comparison with the Duchenne dystrophy, at least in so far as most affected individuals live into adulthood. It was described originally by Emery and Dreifuss and subsequently by Hopkins and by Merlini and their colleagues. The primary gene defect is a deficiency of the protein emerin, a constituent of the nuclear membrane, encoded by EMD on the X chromosome (Fig. 45-3). However, also described are autosomal dominant forms with mutations in the gene for laminin A/C (called LGMD 1B, obviously affecting both girls and boys), an additional X-linked form due to mutations in FHL-1 as well as sporadic and dominant mutations of other genes encoding for entirely disparate proteins. Making a complete understanding of this syndrome even more complex is the recent appreciation that many of cases have none of these mutations.
The age of onset varies from childhood to late adolescence or adulthood. Weakness affects first the upper arm and pectoral girdle musculature and later the pelvic girdle and the distal muscles in the lower extremities. The distinguishing feature of the most typical form of the disease is the early appearance of contractures in the flexors of the elbow, extensors of the neck, and posterior calf muscles. Facial muscles are affected occasionally. There is no hypertrophy or pseudohypertrophy, and cognition is unaffected. However, severe cardiomyopathy with variable sinoatrial and atrioventricular conduction defects is a common accompaniment.
The course of the myopathy is generally benign, more like that of Becker dystrophy, but weakness and contractures are severe in some cases and sudden cardiac death is a not infrequent occurrence. For this reason, close monitoring by a cardiologist and the prophylactic insertion of a pacemaker at the appropriate time may be lifesaving.
The less common types of Emery-Dreifuss dystrophy, as mentioned, may have a scapuloperoneal (FHL-1 gene) or humeroperoneal (laminin mutation).
Facioscapulohumeral Muscular Dystrophy (FSH, Landouzy-Dejerine Muscular Dystrophy, DUX4 Mutation)
This is a slowly progressive dystrophy involving primarily the musculature of the face and shoulders, often with long periods of nearly complete arrest. The pattern of inheritance is usually autosomal dominant. Almost all are of the facioscapulohumeral muscular dystrophy 1 (FSHD1) type; 5 to 10 percent are designated FSHD2, for which the mutation has recently been identified. The clinical presentations are very similar.