Coexistence of X-linked recessive Emery-Dreifuss muscular dystrophy with inclusion body myositis-like morphology

Abstract

We reported three cases (two familial and one sporadic) of X-linked Emery-Dreifuss muscular dystrophy (EDMD), genetically documented. Two patients demonstrated a typical inclusion body myositis (IBM)-like morphology. The third patient had only minor changes. Patients had elbow and ankle contractures, progressive wasting of humeroperoneal muscles and cardiac failure (pacemaker implantation in all). There was a mutation within the Xq28 gene and complete absence of emerin in the nuclear membrane. Mononuclear cell infiltrations, rimmed vacuoles, amyloid deposits, as well as cytoplasmic and nuclear tubulofilamentous muscle inclusions were most unusual findings. Coexistence of IBM-like morphology and X-linked recessive EDMD might indicate that pathological features of IBM are nonspecific and may be present in other neuromuscular disorders.

Pathophysiology of inflammatory and autoimmune myopathies

“…These proteins may accumulate in the cytoplasm of muscle fibers due to malfunctioning of the proteasome machinery, direct toxicity of monomers or oligomers of aberrant proteins and generation of cell stress, as described by Askanas et al [1][2][3]7]. Many of the noted accumulations however do not appear specific for IBM because they are also found in other vacuolar myopathies especially myofibrillar, hereditary IBM or even in chronic neurogenic conditions such as the postpolio syndrome [89][90][91][92][93][94][95][96]. Autophagic processing, which is relevant to degradation of intracellular proteins, may also play a role since the vacuoles have autophagic properties [97] involved in processing of APP/ b-amyloid.…”

Nuclear membrane proteins are present within rimmed vacuoles in inclusion‐body myositis

“…VCP has a range of postulated functions that include nuclear assembly,18, 29 but the precise mechanism of disease in IBMPFD has not been determined. Rimmed vacuoles have also been reported in Emery–Dreifuss muscular dystrophy associated with emerin mutations 15. Our findings in IBM together with these observations in other disorders suggest that rimmed vacuoles may be lesions closely associated with nuclear abnormalities.…”

Untangling the complexity of limb‐girdle muscular dystrophies

“…An implantable cardioverter‐defibrillator (ICD) has been shown to be effective in preventing sudden cardiac death due to ventricular arrhythmias in patients with laminopathy . Rimmed vacuoles are common in transportinopathy‐3, but are only rarely reported in emerinopathy and laminopathy …”