Inflammatory myopathy in the context of an unusual overlapping laminopathy.

Cristina Guillín-Amarelle,David Araújo-Vilar,Sofía Sánchez-Iglesias,Elena Pintos,Antonio Mera,Julio Pardo,Felipe F Casanueva,Leticia Rodríguez-Cañete,Ana Castro-Pais

doi:10.20945/2359-3997000000048

Cristina Guillín-Amarelle, David Araújo-Vilar + Show 7 more

Open Access

https://doi.org/10.20945/2359-3997000000048

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Abstract

Laminopathies are genetic disorders associated with alterations in nuclear envelope proteins, known as lamins. The LMNA gene encodes lamins A and C, and LMNA mutations have been linked to diseases involving fat (type 2 familial partial lipodystrophy [FPLD2]), muscle (type 2 Emery-Dreifuss muscular dystrophy [EDMD2], type 1B limb-girdle muscular dystrophy [LGMD1B], and dilated cardiomyopathy), nerves (type 2B1 Charcot-Marie-Tooth disease), and premature aging syndromes. Moreover, overlapping syndromes have been reported. This study aimed to determine the genetic basis of an overlapping syndrome in a patient with heart disease, myopathy, and features of lipodystrophy, combined with severe metabolic syndrome. We evaluated a 54-year-old woman with rheumatoid arthritis, chronic hypercortisolism (endogenous and exogenous), and a history of cured adrenal Cushing syndrome. The patient presented with a complex disorder, including metabolic syndrome associated with mild partial lipodystrophy (Köbberling-like); mild hypertrophic cardiomyopathy, with Wolff-Parkinson- White syndrome and atrial fibrillation; and limb-girdle inflammatory myopathy. Mutational analysis of the LMNA gene showed a heterozygous c.1634G>A (p.R545H) variant in exon 10 of LMNA. This variant has previously been independently associated with FPLD2, EDMD2, LGMD1B, and heart disease. We describe a new, LMNA-associated, complex overlapping syndrome in which fat, muscle, and cardiac disturbances are related to a p.R545H variant.

Highlights

Mutations in the LMNA gene (NM_170707.2) have been associated with a broad spectrum of diseases [1], including type 2 familial partial lipodystrophy (FPLD2), LMNA-related metabolic syndrome, type 2 Emery–Dreifuss muscular dystrophy (EDMD2), type 1B limb-girdle muscular dystrophy (LGMD1B), conduction-system diseases and dilated cardiomyopathy (DCM1A), and progeroid syndromes
The LMNA gene encodes lamins A and C, and LMNA mutations have been linked to diseases involving fat, muscle, nerves, and premature aging syndromes
This study aimed to determine the genetic basis of an overlapping syndrome in a patient with heart disease, myopathy, and features of lipodystrophy, combined with severe metabolic syndrome

Summary

Introduction

Mutations in the LMNA gene (NM_170707.2) have been associated with a broad spectrum of diseases [1], including type 2 familial partial lipodystrophy (FPLD2), LMNA-related metabolic syndrome, type 2 Emery–Dreifuss muscular dystrophy (EDMD2), type 1B limb-girdle muscular dystrophy (LGMD1B), conduction-system diseases and dilated cardiomyopathy (DCM1A), and progeroid syndromes. FPLD2 begins in women during puberty, with a phenotype of fat loss in the limbs and buttocks, fat accumulation in the face and neck, well-defined musculature, phlebomegaly, insulin resistance, atherogenic dyslipidemia, and high cardiovascular risk [2]. The differential diagnosis includes Cushing’s syndrome and truncal obesity. Previous studies have described a LMNA-associated metabolic syndrome with a Köbberling-like fat distribution [3,4]. EDMD2 is characterized as a progressive skeletal muscle weakness associated with early joint contractures. LGMD1B causes muscular weakness in the spine and pelvic girdle [1]

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