To describe a case of Charcot-Marie-Tooth Disease Type 2Z caused by MORC2 gene mutation characterized by respiratory insufficiency.

Charcot-Marie-Tooth disease (CMT) is a heterogenous group of hereditary neuropathies, with diversity in pathogenesis and clinical manifestations. Respiratory symptoms due to diaphragmatic dysfunction in CMT are rare but have been described. In 2016, the MORC2 gene was implicated in a family with hereditary axonal sensorimotor polyneuropathy. Additional reports have since expanded the phenotype associated with this gene mutation. Some of the unusual characteristics reported have included proximal limb involvement, intellectual disability, and imaging evidence of cerebellar atrophy and white matter changes. Respiratory insufficiency has been described in one patient with MORC2 gene mutation who had a spinal muscular atrophy-type phenotype, but to our knowledge, has not been reported in any of the sensorimotor neuropathy cases.

A literature review was performed in PubMed for published cases of MORC2 gene-related CMT.

A 28 year-old woman presented with progressive leg weakness, gait dysfunction, and dyspnea since childhood. Her neurologic exam was significant for distally-predominant weakness, length-dependent vibration loss, and reduced deep tendon reflexes throughout. Nerve conduction studies and electromyography revealed a symmetric, length-dependent polyneuropathy with primarily axonal involvement. Pulmonary function testing demonstrated low maximal inspiratory pressure, low maximal expiratory pressure, and cough peak flow, which is consistent with a neuromuscular etiology. Genetic testing revealed a pathologic variant in exon 9 of the MORC2 gene (c.754C>T.; p.Arg252Trp also known as p.Arg190Trp).

Respiratory insufficiency is a rare complication of Charcot-Marie-Tooth disease, which has previously been described in CMT1A, and may also be one of the clinical features that sets CMT2Z apart. Patients should be screened appropriately for respiratory dysfunction to help guide diagnosis, ensure the best possible outcome, and further characterize this group of diseases.