Co‐morbidity of Emery–Dreifuss muscular dystrophy and a congenital myasthenic syndrome possibly affecting the phenotype in a large Bedouin kindred

Abstract

Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked humero-peroneal muscular dystrophy associated with contractures and cardiomyopathy. In a 90 member family, we found 11 affected male individuals, three of whom displayed areflexia and neurogenic electromyographic changes. Muscle biopsy performed in one case demonstrated type grouping suggestive of a neurogenic disorder. These three individuals and another family member, who suffers from mild, static limb weakness but is clinically and genetically unaffected by EDMD showed an abnormal incremental response of over 100% to tetanic stimulation. In contrast, one affected family member showed myopathic features on needle electromyography and no definite pathology in repetitive stimulation studies. The diagnosis of EDMD was established by demonstrating a 1712_1713insTGGGC mutation in the emerin gene. This family apparently expresses co-morbidity of EDMD with an exceptionally mild form of pre-synaptic congenital myasthenic syndrome resembling the Lambert-Eaton myasthenic syndrome (LEMS). The superimposed pre-synaptic disorder may have contributed to the development of the neurogenic features demonstrated in these patients.

X-linked Emery–Dreifuss muscular dystrophy manifesting with adult onset axial weakness, camptocormia, and minimal joint contractures

“…It is noteworthy that any muscular condition associated with cardiac arrhythmias in early adulthood should guide to diagnosis of conditions affecting the nuclear membrane and other arrhythmogenic cardiomyopathies. Among the 6 reported patients, 2 had muscle biopsy that, similarly to our patient, showed non dystrophic findings including atrophic muscle fibers [22], type grouping and type 1 fiber predominance [20] with absent emerin [21]. Of note we describe the absence of type 2B fibers that was not reported previously.…”

“…The majority (66.6%) harbor truncating mutations (out-of-frame large or small deletions/insertions, nonsense mutations) causing absent or rarely faint emerin (out-of-frame large or small deletions/insertions, nonsense mutations) with western blot studies. The mutation harbored by our patient is a 5 nucleotides (TGGGC) duplication introducing a frameshift after aminoacid 218, was already reported in 6 affected individuals from 3 families of German, Japanese and Israeli origin [20][21][22]. None of them had camptocormia.…”

“…None of them had camptocormia. These patients presented a typical EDMD phenotype with elbows and ankles contractures [20] in association with stiff neck in one case [22]. Cardiac involvement was always present, varying from 1 st degree to complete atrio-ventricular block requiring pacemaker with supraventricular arrhythmias and heart dilation.…”