# Hereditary Myopathy With Early Respiratory Failure Associated With an Incidental COL4A5 Variant: A Case Report

## TL;DR

A man with muscle weakness and breathing issues was diagnosed with a rare genetic disorder, with an additional unrelated gene variant found.

## Contribution

This case report highlights the importance of genomic testing in diagnosing rare neuromuscular disorders and interpreting incidental genetic findings.

## Key findings

- A pathogenic TTN variant confirmed hereditary myopathy with early respiratory failure (HMERF) in a patient.
- An incidental COL4A5 variant was detected but lacked clinical correlation.
- Genomic testing was crucial for diagnosing an atypical neuromuscular presentation.

## Abstract

Hereditary myopathy with early respiratory failure (HMERF) is a rare autosomal dominant disorder caused by TTN variants. COL4A5 mutations are linked to X‐linked Alport syndrome.

A 34‐year‐old male developed progressive lower limb weakness, gait disturbance, nocturnal hypoventilation, and calf hypertrophy. Family history revealed similar symptoms in his mother and sister. Examination showed absent reflexes; MRI demonstrated muscle atrophy and fatty replacement; needle electromyography (EMG) was performed and showed findings consistent with advanced myopathy; however, it was not used as a primary diagnostic tool. Whole‐exome sequencing identified a pathogenic TTN variant (c.95126C > G, p.Pro31709Arg), confirming HMERF. A hemizygous COL4A5 variant (c.4891C > T, p.Arg1631Cys) was also detected but lacked clinical correlation.

This case illustrates a classic HMERF phenotype confirmed genetically, with an incidental COL4A5 variant of uncertain significance. It underscores the importance of genomic testing in atypical neuromuscular presentations and the need for cautious interpretation of incidental findings.