Titinopathy, an atypical respiratory failure

BMJ Case Rep. 2020 Sep 9;13(9):e235378. doi: 10.1136/bcr-2020-235378.


Hereditary myopathy with early respiratory failure is a neuromuscular disease with an autosomal dominant inheritance pattern. Clinical presentation is characterised by proximal and distal muscle weakness, exertional dyspnoea and generalised fatigue. There is no disease-modifying therapy and the prognosis is unknown. Herein we present a case of a 40-year-old woman with long-standing asthenia and apathy and, more recently, daytime sleepiness, dyspnoea and difficulty in walking. A hypercapnic respiratory failure with severe acidemia was identified. The muscle biopsy showed the presence of cytoplasmatic bodies and rimmed vacuoles, suggestive of a hereditary myopathy with early respiratory failure disease. The genetic study confirmed this diagnosis identifying a heterozygous mutation on c.95134T>C (p.Cys31712Arg) in exon 343 in the titin gene. The patient was discharged home under supportive treatment with non-invasive ventilation.

Keywords: muscle disease; neurology; neuromuscular disease; respiratory medicine.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Asthenia* / diagnosis
  • Asthenia* / etiology
  • Biopsy / methods*
  • Connectin / genetics*
  • Diagnosis, Differential
  • Dyspnea* / diagnosis
  • Dyspnea* / etiology
  • Female
  • Genetic Diseases, Inborn* / diagnosis
  • Genetic Diseases, Inborn* / genetics
  • Genetic Diseases, Inborn* / physiopathology
  • Humans
  • Muscle Weakness* / diagnosis
  • Muscle Weakness* / etiology
  • Muscle, Skeletal / pathology*
  • Muscular Diseases* / diagnosis
  • Muscular Diseases* / genetics
  • Muscular Diseases* / physiopathology
  • Mutation
  • Palliative Care
  • Respiratory Insufficiency* / diagnosis
  • Respiratory Insufficiency* / genetics
  • Respiratory Insufficiency* / physiopathology


  • Connectin
  • TTN protein, human

Supplementary concepts

  • Hereditary Myopathy with Early Respiratory Failure