Hereditary myopathy with early respiratory failure (HMERF): Still rare, but common enough

Abstract

Phenotypic and genetic/allelic heterogeneity is a feature of many neuromuscular disorders, titinopathies being one of them. Hereditary Myopathy with Early Respiratory Failure (HMERF) has been considered an extremely rare disease with definite clinicopathologic hallmarks, and geographically restricted to the Northern European population with one single titin gene defect identified in previous years. The recent availability of massive parallel sequencing techniques, allowing the screening of all coding regions of the genome in undiagnosed patients, together with a growing awareness of the main muscle MRI features of the disease, has led to the discovery of a number of HMERF families and new titin mutations in the last five years. We reviewed the clinical, pathological and muscle imaging findings that are still cornerstones for the diagnosis of this disease, as well as the most recent molecular genetic findings. HMERF is more common and geographically widespread than previously expected, and the knowledge of the whole phenotypic and molecular spectrum of HMERF can increase the number of diagnosed patients considerably.

Characterization of Chinese patients with myofibrillar myopathy from a single center: expanding the clinico-genetic spectrum

“…The c. 95134T>C missense mutation of patient 14 was first associated with HMERF in three Scandinavian families [3] and later in various ethnic groups including the Chinese population [4][5][6][7][8][9][10]. It is noteworthy that over 100 reported cases of HMERF, peripheral nerves were considered spared [31]. Our patient is the first HMERF patient that shows peripheral nerve involvement, which is consistent with an axonal sensorimotor polyneuropathy pattern.…”

Is Gene-Size an Issue for the Diagnosis of Skeletal Muscle Disorders?

“…Mutations in the last exons can result in a dominant form, the Tibial Muscular Dystrophy, a late onset distal myopathy [20]. Missense mutations in a specific exon (exon 344) have been associated with an adult onset hereditary myopathy with early respiratory failure (HMERF) [21,22].…”

Clinical Reasoning: A 54-year-old man with dyspnea and muscle weakness

“…Differential diagnoses include adult Pompe disease, myofibrillar myopathies, limb-girdle muscular dystrophy, facioscapulohumeral muscular dystrophy, mitochondrial myopathies, myasthenia gravis, and amyotrophic lateral sclerosis. 2,10 There is no disease-modifying treatment; therapy includes the use of orthoses and mobility aids, physiotherapy, and respiratory support. 10 Our case highlights the importance of considering early neuromuscular respiratory insufficiency as a distinctive syndrome leading to a challenging and broad differential diagnosis.…”

“…2,10 There is no disease-modifying treatment; therapy includes the use of orthoses and mobility aids, physiotherapy, and respiratory support. 10 Our case highlights the importance of considering early neuromuscular respiratory insufficiency as a distinctive syndrome leading to a challenging and broad differential diagnosis. Identifying the underlying condition has implications regarding specific and symptomatic treatment.…”