Rare Respiratory Complications Found in Man With CMT2A

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Multiple respiratory complications, including a collapsed lung and diaphragm dysfunction, were identified in a man with Charcot-Marie-Tooth disease type 2 (CMT2) that was associated with an MFN2 gene mutation, according to a recent case study.

“To our knowledge, this is the first demonstration of a CMT patient carrying an MFN2 gene abnormality with multiple respiratory complications, thus raising a possibility that MFN2 dysfunction might cause several types of respiratory disorders,” the researchers wrote.

The report, “Multiple respiratory complications in a patient with Charcot-Marie-Tooth disease with MFN2 mutation,” was published in Respiratory Medicine Case Reports.

CMT2 is caused by genetic mutations that disrupt the structure and function of axons, the projections on nerve cells that transmit signals to the muscles and other nerves. Common symptoms include muscle wasting and decreased sensations. Respiratory problems are rarely reported.

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Mutations in MFN2 are the most common cause of CMT2, accounting for about 25% of cases. CMT2 caused by MFN2 mutations are classified as the 2A CMT subtype (CMT2A).

Researchers from Japan reported a 49-year-old man who had been diagnosed with CMT in childhood and whose symptoms included difficulty walking and damage to his motor and sensory nerves. He also had muscle loss that had progressively worsened, limb deformities, and no deep tendon reflexes.

Based on these symptoms, the man had been diagnosed with CMT, which was confirmed with a MFN2 mutation found on genetic testing.

The man continued to experience worsening muscle weakness and lost his ability to walk at age 18. He became wheelchair-dependent at 30 and began to feel shortness of breath at 46, when he started waking up in the night with excessive sweating.

He arrived at the researchers’ clinic complaining of extreme weight loss. A physical exam revealed that his chest appeared sunken (funnel chest).

Chest imaging showed dysfunction of the diaphragm, the muscle involved in pulling air into the lungs during breathing. Normally, the diaphragm moves to allow air into the lungs, however, the man’s diaphragm was motionless, particularly on his right side.

He also had a collapsed lung, which occurs when air escapes and puts pressure outside the lung, preventing it from expanding during breathing. He also had cysts, which may have caused the collapse.

The movement of the diaphragm is controlled by the phrenic nerve, which runs from the neck to the diaphragm. In nerve function tests, stimulation of the phrenic nerve did not cause the man’s diaphragm to move, meaning the nerve was paralyzed, the researchers said.

The man’s breathing ability was significantly restricted, consistent with his diaphragm abnormalities.

Polysomnography, a test used to monitor brain activity during sleep, showed that the man had mild sleep apnea, which happens when breathing intermittently stops and starts again during sleep. His oxygen levels reached as low as 79% while he slept.

Non-invasive positive pressure ventilation therapy (NPPV), which helps a person breathe through the use of a tight-fitting mask that delivers oxygen, was introduced and the man’s sleep problems eased.

According to the team, this patient was unique, as both diaphragm dysfunction and thoracic abnormalities are rare in CMT2A patients.

While rare, the few other CMT cases that have described respiratory issues have often involved phrenic nerve paralysis, but no other cases have reported collapsed lungs. Diaphragm dysfunction, while relatively common in other CMT types, including types 1, 2C, and 4, is not typical for CMT2A, the researchers noted.

They hypothesized the man’s MFN2 mutation is linked to his respiratory symptoms, but noted that it’s possible he has other genetic mutations that have not yet been identified that account for some of his symptoms.

“It would be helpful for pulmonologists and neurologists to be aware of these facts in patients with CMT, because respiratory complications in patients with CMT might be more frequent than expected. A careful examination should be performed if respiratory symptoms including [breathing difficulty] are observed in CMT patients in clinical settings,” they concluded.