Objective:

To describe a case of hereditary myopathy with early respiratory failure (HMERF)  and discuss reported cases of this condition.

Background:

 HMERF is a rare myopathy resulting from a mutation on the TTN region of the titin gene. It can be confused with other diseases presenting with early respiratory complaints like amyotrophic lateral sclerosis, myasthenia gravis and adult onset Pompe disease. Thus, a high degree of suspicion should be maintained for an adequate diagnosis. A case report and a thorough review of PubMed-reported cases were conducted.

Design/Methods:

A 53-year-old male reported progressive lower extremity weakness and dyspnea. Previous pulmonary function tests and chest fluoroscopy showed a restrictive pattern and reduced diaphragmatic movement, respectively. On examination, he had  steppage gait and muscle strength was reduced in anterior tibialis, iliopsoas and hamstring muscles. Electromyography showed myopathic findings in iliopsoas and gastrocnemius muscles. A lumbar MRI demonstrated patchy fatty atrophy of iliopsoas and lumbar paraspinals muscles. Next generation sequencing revealed a heterozygous titin gene (TTN) mutation c.95187G> C (p.Trp31729Cys) consistent with the diagnosis of HMERF.

Results:

24 cases of HMERF( 18-74 years old ) were identified.. The earlier age of onset was 14 years. Most cases presented with limb muscle weakness but 8 began with an initial respiratory complaint. Dyspnea and nocturnal symptoms of hypoxia were prominent and pulmonary function tests reveal a restrictive pattern with a reduced forced vital capacity.  The diagnosis was made primarily based on genetic findings although EMG showing myopathic changes and muscle biopsy showing cytoplasmic bodies and rimmed vacuoles provide additional diagnostic support. On average, patients required non-invasive ventilation 3.5 years post-symptom onset.

Conclusions:

HMERF should be considered in the differential diagnosis of an adult with concomitant respiratory and limb muscle weakness.