Dreifuss and Hogan are credited with the initial groundwork on EDMD, when in 1961 they described an unusual X-linked form of MD in a large family with muscle wasting disease initially thought to be milder forms of Duchenne and Becker muscular dystrophies [10]. It was only in 1966 that Alan Emery and Fred Dreifuss identified EDMD as a separate disease entity [11].
Emery-Dreifuss muscular dystrophy is a rare type of muscular dystrophy with a worldwide incidence of 1 in 100,000, often presenting in late childhood and adulthood [3, 4]. It has three main genetic patterns; X-linked recessive, autosomal dominant, and autosomal recessive [5, 6]. The X-linked EDMD is the most common pattern, occurring due to mutation in the emerin gene chromosomes (Xq28) [5]. Emerin protein is located in the inner nuclear membrane of body cells, dominant in skeletal and cardiac muscles [12]. Mutation in the emerin gene causes premature termination of translation in emerin mRNA affecting protein synthesis, and causing aberration of nuclear functioning [12]. The autosomal dominant and recessive patterns of EDMD are due to mutations of the Lamin A/C genes [6]. Lamin A/C proteins forms part of the inner nuclear membrane, important in the mechanical stability of the nuclear envelop [13] and cell signalling [14].
Skeletal muscle involvement in EDMD present clinically with early contractures (involving the ankles, elbows, para-spinal muscles), weakness and wasting of scapulohumeropareoneal pattern [7, 8]. Muscles weakness may occur at the second decade and may be preceded by contractures. The main muscles affected are biceps, paravertebral, glutei, semitendinosus, adductor major, and gastrocnemius [15]. Walking difficulties and gait disturbances like in our case are common in autosomal dominant EDMD [16]. Cardiac conduction abnormalities and cardiomyopathy are the main cardiac complications of EDMD [17]. Cardiac conduction abnormalities common in EDMD include; supraventricular, and ventricular tachyarrhythmia, and atrio-ventricular block [17]. The presence of cardiac arrhythmias like in our case necessitates expert cardiologist consultation. Cardiomyopathies (more common in the autosomal dominant EDMD) [16] is a primary cause of heart failure and usually precedes cardiac arrhythmias.
Muscular dystrophies similar to EDMD include; Duchenne muscular dystrophy (DMD), Becker dystrophy (BMD), congenital muscular dystrophies, FSHD, LGMD [8]. The presence of weakness, hypotonia, and difficulty in running, jumping, or calf hypertrophy [18] should prompt investigation of DMD. However, these findings were absent in our patient. Also the scarcity of contractures in DMD [18] makes it less likely. Other possible diagnosis like congenital myopathies usually present with hypotonia and weakness at the neonatal period, which is not the case in our patient. Physical abnormalities like facial abnormalities, high palate, scoliosis, and delayed developmental mile stones are common in congenital myopathies [18], but absent in our patient. Fascio-scapula-humeral muscular dystrophy (FSHD) a dominantly inherited muscular dystrophy was a potential differential in our case. However, its association with facial weakness (ability to close the eyes tightly, or smile), slow progression of weakness, mental retardation, and absence of contractures made it less likely [18]. Limb-girdle muscular dystrophy (LGMD), another genetic form of muscular dystrophy is similar to EDMD. It predominantly causes weakness of the lower extremities. Although girdle, shoulder and neck muscle weakness can occur [18], contractures are less likely. Poliomyelitis usually presents with flaccid paralysis, making it less likely in our case.
Creatine kinase levels are normal or mildly elevated (<5 times the upper limit) in EDMD, as evident in our case. CK levels greater than 10 times the upper limit are associated with DMD, and BMD [19]. EMG is not required for diagnosis [20, 21]. Histological findings are nonspecific, displaying variability in muscle fibre diameters [20] as in our case. Molecular genetic studies are used to detect mutations of the genes. ECG and echocardiography play vital roles to diagnose cardiac complications. A team approach involving a neurologist, pulmonologist, cardiologist, orthopedic surgeon, physical therapist, and counsellors ensures quality care. Emphasis is laid on surgical and nonsurgical management of contractures, and pacemaker implantations to prevent sudden death from cardiac complications [21].
Our case emphasizes the importance of community outreach programs in the recognition of rare diseases like EDMD, as this was the historical background in the discovery of this disease [10]. Although EDMD has no definitive treatment, early diagnosis and interventions play an important role in improving the wellbeing of the patients [22]. Early recognition of EDMD helps in minimizing contractures through early physical therapy and stretching exercises [22]. However, this was not the case in our patient as the contractures had markedly progressed resulting in the patient being handicapped and consequently bed bound. Also the presence of cardiac signs on ECG puts the patient at risk of sudden death from cardiac complications like arrhythmias and other cardiac myopathies. Early recognition of these cardiac complications is required for timely cardiac interventions like pacemaker implantation to prevent sudden cardiac death [22]. Genetic and clinical screening of family members is also warranted as it plays an important role in early recognition of family members at risk [22]. However, genetic studies were not done in our case because of limited resources. Furthermore, scientific research in recognizing the genes, mutations, and risk factors associated with EDMD should be encouraged in the development of novel gene therapies in the management of EDMD. The development and support of organizations involved in the recognition, awareness and management of muscular dystrophies in resource limited settings will play a good role in finding and assisting poor children with EDMD.
Emery-Dreifuss muscular dystrophy is a rare disabling genetic muscular disease, and a cause of paralysis, and sudden death from cardiac complications. A high index of suspicion is required, to pose a diagnosis in patients with paralysis in resource limited settings. Prompt diagnosis and management is essential to prevent the progression of cardiac and orthopedic complications and improve the prognosis of this disease.
