Patients with Charcot-Marie-Tooth disease (CMT) type 2S may benefit from lifelong respiratory surveillance, a case report suggests.
The study, “Charcot Marie Tooth disease type 2S with late onset diaphragmatic weakness: An atypical case,” was published in the journal Neuromuscular Disorders.
CMT2S is caused by genetic mutations in the IGHMBP2 gene. But more than 60 mutations in this gene have also been linked to spinal muscular atrophy with respiratory distress type 1 (SMARD1), which is fatal for most infants before they’ve reached a year old.
As opposed to SMARD1, which is characterized by nerve cell damage and diaphragmatic weakness, CMT2S has not been associated with respiratory dysfunction but rather manifests by slowly progressive weakness and sensory loss.
In a recent case study, U.K. researchers reported an atypical case of CMT2S involving a boy who developed diaphragm (respiratory muscle) weakness at 9 years old.
The boy had an unremarkable perinatal history and did not have any alterations in the first examinations performed at birth and six weeks after birth. He had no family history of neurological problems.
At 6 months old, he started to develop deformities in both feet without alteration of the upper limbs. At 15 months, he underwent surgery to correct his foot deformities by releasing his Achilles tendon, followed by putting the leg in plaster, and boots and bar treatment, for resolving ankle contractures.
When he was 21 months old, he started to also develop upper limb involvement, with his hands persistently in a clawed posture. By 2 years old, he was able to walk with support, but he never achieved independent walking.
He showed progressive weakness in both his upper and lower limbs, and was dependent on a wheelchair by the time he was 8. At 11 years old, he showed muscle weakness, affecting the distal limbs more severely, and he also had poor trunk and head control. At this point, he also showed mild learning difficulties.
Throughout his development, he was disinterested in food and always had a small appetite, leading to a low weight and requiring him to be fed with the help of a tube inserted into the stomach at 7 years old.
Evaluation of the response of his nerve fibers revealed that he had very small motor responses, and had absent or very small and slightly delayed sensitivity in his lower and upper limbs. These clinical findings were consistent with a diagnosis of CMT.
Genetic analysis showed that he had two mutations in the IGHMBP2 gene that had been inherited from his healthy parents. One of the identified mutations had already been reported in CMT2 and SMARD1 patients, while the other variant had not previously been described.
By 8 years old, he started to develop a rapidly progressive S-shaped spinal curvature, and he also started to lose control of his head. With the appearance of these new manifestations, the clinical team started to follow the progression of his respiratory function, measured by forced vital capacity (FVC) every six months and an annual sleep study.
At this point, he had reasonable lung function, with FVC at about 51% of what was expected for his health status and with normal breathing patterns.
At 9 years old, after a family trip abroad, he developed a chest infection with abnormal accumulation of liquids in the left side. Although the problem was resolved after the liquid was drained and the lung could inflate normally, he continued to struggle to breathe, an issue that worsened with the use of a brace for his spine curvature.
His FVC levels deteriorated to only 19% of expected values, and a marked deterioration was also noted in his breathing pattern. Given his severe respiratory impairment, he started immediately to breathe through a mask BiPAP ventilation system. With this respiratory support, he showed a slight improvement in FVC and gas exchange values.
By 10.4 years of age, his respiratory function deteriorated again so he underwent urgent spinal surgery.
Previous studies have reported that CMT2S is a less severe condition than SMARD1 due to residual IGHMBP2 protein function. However, this is the first reported case of a CMT2S patient with paralysis of the diaphragm.
The clinical team believes that the respiratory failure in this patient could be due not only to the evolving diaphragmatic weakness that was not effectively diagnosed but also because of his rapidly progressive scoliosis.
“This emphasizes the importance of regular respiratory surveillance for patients with CMT2S,” they said.