# Undetected Neuromuscular Disease in Patients after Heart Transplantation

## TL;DR

Some heart transplant patients may have undiagnosed neuromuscular diseases that affect both heart and muscle function.

## Contribution

This study identifies genetic causes of muscle weakness in heart transplant patients using exome sequencing and clinical assessments.

## Key findings

- Seven out of 39 patients reported new-onset muscle weakness and motor limitations.
- Three patients had genetic variants in genes related to muscle function like nexilin, myosin heavy chain, and SPG7.
- 10% of patients showed clinical signs of myopathy potentially due to genetic causes.

## Abstract

(1) Heart transplantation (HTX) improves the overall survival and functional status of end-stage heart failure patients with cardiomyopathies (CMPs). The majority of CMPs have genetic causes, and the overlap between CMPs and inherited myopathies is well documented. However, the long-term outcome in skeletal muscle function and possibility of an undiagnosed underlying genetic cause of both a cardiac and skeletal pathology remain unknown. (2) Thirty-nine patients were assessed using open and standardized interviews on muscle function, a quality-of-life (EuroQol EQ-5D-3L) questionnaire, and a physical examination (Medical Research Council Muscle scale). Whole-exome sequencing was completed in three stages for those with skeletal muscle weakness. (3) Seven patients (17.9%) reported new-onset muscle weakness and motor limitations. Objective muscle weakness in the upper and lower extremities was seen in four patients. In three of them, exome sequencing revealed pathogenic/likely pathogenic variants in the genes encoding nexilin, myosin heavy chain, titin, and SPG7. (4) Our findings support a positive long-term outcome of skeletal muscle function in HTX patients. However, 10% of patients showed clinical signs of myopathy due to a possible genetic cause. The integration of genetic testing and standardized neurological assessment of motor function during the peri-HTX period should be considered.