Dr. Worman of Columbia University received equity from AlloMek Therapeutics and honorariums from MNG Laboratories for scientific advisory board membership.)
Dr. Ciafaloni of the University of Rochester received consulting fees from Biogen and Pfeizer and research grants from Sarepta and Santhera.)
This article includes discussion of Emery-Dreifuss muscular dystrophy, EDMD, Emery-Dreifuss syndrome, X-linked Emery-Dreifuss muscular dystrophy, and autosomal dominant Emery-Dreifuss muscular dystrophy. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
Emery-Dreifuss muscular dystrophy is a syndrome classically characterized by (1) slowly progressive muscle weakness and wasting in a scapulo-humeroperoneal distribution, (2) early contractures of the elbows, ankles, and posterior neck, and (3) dilated cardiomyopathy with conduction defects. Originally described as an X-linked disorder, Emery-Dreifuss muscular dystrophy-like phenotypes can arise from mutations in both autosomal and X chromosome genes including those encoding emerin and A-type lamins as well as in less frequent cases those encoding nesprin1, nesprin2, SUN1, SUN2, four-and-a-half-LIM protein 1, LUMA, and lamina-associated polypeptide 1. Although the skeletal muscle involvement can vary as a result of mutations in these genes, cardiomyopathy is the most prevalent and potentially life-threatening feature.
• Emery-Dreifuss muscular dystrophy can be inherited in an X-lined or autosomal manner and result from mutations in several different genes.
• Variations in the classical Emery-Dreifuss phenotype can occur as a result of mutations in the causative genes.
• Emery-Dreifuss muscular dystrophy should be considered in patients with muscular dystrophy and cardiac disease.
• Cardiomyopathy and conduction defects may require early intervention, and cardiologists should evaluate affected patients.
Historical note and terminology
Céstan and LeJonne at l'Hôpital de la Salpêtrière in Paris published what may have been the first case reports of Emery-Dreifuss muscular dystrophy at the beginning of the twentieth century (Céstan and LeJonne 1902). Emery and Dreifuss were the first to fully describe the X-linked form of the disease in a kindred from Virginia (Emery and Dreifuss 1966). Rowland and colleagues at Columbia University in New York reported an additional case in 1979 and applied the term "Emery-Dreifuss type” muscular dystrophy (Rowland et al 1979). Cases of autosomal inheritance were subsequently reported in the mid 1980s, showing this phenotype to derive from different genetic mutations (Miller et al 1985; Takamoto et al 1984).
Toniolo and colleagues identified EMD (formerly called STA) as the gene on chromosome Xq28 mutated in X-linked Emery-Dreifuss muscular dystrophy (Bione et al 1994). In 1999, Ketty Schwartz and collaborators demonstrated that mutations in LMNA on chromosome 1q21.3 cause autosomal dominant cases of Emery-Dreifuss muscular dystrophy (Bonne et al 1999). The protein products of these genes are localized to the nuclear envelope of virtually all somatic cells. Case reports have further implicated mutations in genes encoding other nuclear envelope proteins as causing Emery-Dreifuss-like phenotypes: mutations in SYNE1 and SYNE2 respectively encoding nesprin1 and nesprin2 (Zhang et al 2007; Chen et al 2017; Zhou et al 2017), TMEM43 encoding LUMA (Liang et al 2011), and TOR1AIP1 encoding lamina-associated polypeptide 1 (Kayman-Kurekci et al 2014), SUN1 and SUN2 (Meinke et al 2014). Mutations in FHL1 encoding four-and-a-half-LIM protein 1, a protein localized to the sarcolemma, sarcomere, and nucleus of muscle cells, have also been reported to cause Emery-Dreifuss muscular dystrophy (Quinzii et al 2008; Gueneau et al 2009). Hence, although historically considered a specific disease, more recent advances in genetics have shown that Emery-Dreifuss muscular dystrophy is best considered a syndrome that can result from alterations in several different genes.
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