Researchers have identified a new type of Charcot-Marie-Tooth disease (CMT): Recessive Intermediate CMT E, or CMTRIE. This rare subtype is caused by mutations in both copies of a gene called KCTD11.
CMTRIE joins a small but growing group of intermediate CMT subtypes. “Intermediate” refers to how fast signals travel through the nerves. In these types of CMT, nerve conduction speeds are not slow enough to be considered demyelinating (CMT1), and not fast enough to be considered axonal (CMT2). Instead, they fall in the middle, typically between 25 and 45 meters per second.
Intermediate classification is based on nerve conduction results only and does not reflect how severe the disease is or how quickly it progresses.
CMTRIE follows an autosomal recessive inheritance pattern. This means that a person must inherit two copies of the mutated gene — one from each parent — to have the condition. Like other types of CMT, symptoms may include muscle weakness, sensory loss, balance problems, and foot deformities. Nerve conduction studies and nerve biopsies (usually performed only in a research setting) may show signs of both axonal and demyelinating changes.
This is the fourth named recessive intermediate CMT subtype, joining:
- CMTRIA, caused by mutations in GDAP1
- CMTRIC, caused by mutations in PLEKHG5
- CMTRID, caused by mutations in COX6A1
Adding CMTRIE to the list helps expand genetic testing options and improves the chances of finding a diagnosis for families who, despite all attempts, do not have a genetic confirmation of their CMT.
This discovery was presented at the 2025 Annual Meeting of the Peripheral Nerve Society (PNS) in Edinburgh, Scotland, this past May, and is currently published as a preprint while undergoing peer review. CMTA is following this research closely and will share updates as more becomes available. You can read the full preprint publication here.
Published on: July 31, 2025