The natural course of dominant intermediate Charcot-Marie-Tooth (CMT) disease neuropathy subtype C includes progressively worsening mobility and quality of life over time, a long-term follow-up study shows.
Titled “Longitudinal 16‐year study of dominant intermediate CMT type C neuropathy,” the study was published in the journal Muscle & Nerve.
Dominant intermediate CMT (DI-CMT) is a rare form of CMT characterized by nerve conduction velocities (the speed with which electrical signals move through nerves) that are “in between” those typically seen in other types of CMT — hence the term “intermediate.” “Dominant” refers to the mode of inheritance; in dominant inheritance, only one mutated gene (out of the two copies people inherit, one from each biological parent) is enough to cause the disease.
There are three subtypes of DI-CMT, depending on the particular gene that is mutated. DI-CMT neuropathy subtype C (DI-CMTC) is associated with mutations in a gene called YARS.
Because DI-CMTC is so rare, little is known about the specific characteristics of the disease or how they change over time.
This study reports clinical data for 13 people in a single family with DI-CMTC (five female, eight male) who underwent clinical evaluation on two occasions: once in 2000, and then again, 16 years later, in 2016. The participants ranged in age from 8 to 77 years old in 2000 and from 24 to 93 years in 2016.
The most common symptom of DI-CMTC in the group was leg weakness, which, according to the researchers, ranged “from occasional tripping to difficulty walking upstairs, uphill, or running.” The most common sign was weakness and atrophy in leg muscles. For reference, a symptom is what a patient reports; a sign is what a healthcare provider observes.
With the exception of cramps and foot deformities, which remained stable over time, all of the reported symptoms and signs progressed over the 16 years between the two evaluations. However, only worsening gait was statistically significant.
This was accompanied by statistically significant decreases in electrical activity within muscles, although this activity remained within the range of what is considered normal on both occasions.
Study participants also answered questions related to quality of life. Compared with what was recorded in 2000, they reported significantly poorer mobility, more pain and discomfort, and worse anxiety and depression in 2016.
Additionally, the number of participants with an impairment score (measurement of how much an individual is impaired) that was at least “moderate” increased from one patient in 2000 to eight patients in 2016.
“In 2000, the CMTNSv2 [Charcot–Marie-Tooth Neuropathy Score second version] score ranged from 0 to 11 (median, 6.08); in 2016, it ranged from 3 to 18,” the authors wrote.
“We demonstrate that, in a large family with DI-CMTC, motor and sensory symptoms and signs slowly progressed and contributed to worsening mobility, pain/discomfort, and [quality of life],” they concluded.