PONM04 Myofibrillar myopathy caused by a mutation in the desmin gene: expanding the phenotype

Abstract

BackgroundMyofibrillar myopathy (MFM) is a group of morphologically distinct muscle disorders, with genetic and phenotypic variability. When a mutation in the desmin gene is found, it is termed a desminopathy. These patients often present with distal muscle weakness in the lower limbs spreading to involve proximal muscle groups. Cardiomyopathy may be a prominent finding. To our knowledge, vocal cord palsy has not been described in this condition.Case DescriptionA 48-year-old man presented at the age of 39 years with progressive, predominantly distal, lower limb weakness and bilateral ankle contractures. He developed a cardiomyopathy and arrhythmias. Three men in his family were similarly affected and passed away in their fifties. Recently, he presented with hoarseness with bilateral vocal cord palsies confirmed on laryngoscopy.Results of InvestigationsLimb EMG confirmed an active myopathic process. The muscle biopsy showed fibre size variation and rimmed vacuoles. Genetic testing identified a heterozygous mutation in the desmin gene (c.1346A>C (p.Lys449Thr)).DiscussionVocal cord palsy has been described in the autosomal dominant myopathy: vocal cord and pharyngeal weakness with distal myopathy (VCPDM). However, it has not been described in association with a desminopathy and therefore expands the phenotype of this myofibrillar myopathy subgroup.

Nebulin binding impedes mutant desmin filament assembly

“…Although desminopathy shows clinical heterogeneity and variable age of onset, recurrent symptoms of this disease include progressive distal myopathy and muscle weakness, arrhythmia, conduction defects, heart failure, cardiomyopathy, dysphagia, and respiratory insufficiency (van Spaendonck-Zwarts et al ., 2010). Of interest, desminopathy is also linked to vocal cord palsy and pharyngeal distal myopathy (Albertyn et al ., 2010). Recognized histological phenotypes such as cytosolic protein aggregates, myofibril dissolution, rubbed-out fibers, and rimmed vacuoles are characteristically found in biopsies from human muscle tissues (Shinde et al ., 2008; Claeys et al ., 2009; McLendon and Robbins, 2011).…”

Clinical and Myopathological Characteristics of Desminopathy Caused by a Mutation in Desmin Tail Domain

“…This substitution has previously been mentioned in one of the patients with myofibrillar myopathy at the Mayo clinic [16] and recently in a short communication describing a single patient [17], but no detailed phenotypic information was provided. The c.1346A>C (p.Lys449Thr) mutation is located in the tail domain of the desmin molecule.…”

Expanding Spectrum of Desmin-Related Myopathy, Long-term Follow-up, and Cardiac Transplantation

“…A summary of all pathogenic or likely pathogenic genetic variants is shown in Table 1, as well as all phenotypes described to date for patients in the literature carrying the same variants as our patients. 5,17,22,[26][27][28][29][30][31][32][33][34] We report 3 novel variants: c.735+1G>C, c.346A>G predicting Asn116Ser, and Arg212Ter in association with DRM. Four variants (Ser46Phe, Ser2lle, Ser46Tyr, and Ser13Tyr) are in the head domain; 1 (Asn116Ser) is in the Coil1A region; 4 (Leu370Pro, Arg406Trp, Arg355Pro, Leu346-Pro) are in the 2B region; and 2 (Lys449Thr, Arg454Trp) are in the tail region.…”