CMTRIE

KCTD11 | 2025

What Is CMTRIE?

CMTRIE is a type of CMT caused by autosomal recessive mutations in the KCTD11 gene. This gene provides instructions for making a protein involved in regulating cellular signaling and protein turnover within nerve cells. Mutations in the KCTD11 gene disrupt this function, leading to impaired nerve signal transmission.

CMTRIE is autosomal recessive, meaning that both copies of the gene must have a mutation to cause this subtype.

Clinical Features

The age of symptom onset in CMTRIE is variable, ranging from childhood to adulthood. Symptoms typically begin in the lower extremities and progress over time to involve the upper limbs. Nerve conduction studies usually show somewhat slowed conduction velocities, consistent with an intermediate form of CMT.

CMTRIE symptoms may include:

  • Weakness in the feet and lower legs
  • Muscle atrophy
  • Foot drop
  • Reduced or absent reflexes
  • Reduced sensation
  • A steppage-style walking pattern
  • Foot deformities, including high arches, and hammertoes (clawed toes)
  • Progressive involvement of the hands and forearms
  • Difficulty with fine motor skills and manual dexterity
  • Additional symptoms not listed here

Disease Course

CMTRIE shows wide variability in severity and progression. Some individuals are mildly affected, while others develop a more severe disease. Disease progression is generally slow, and life expectancy is not reduced.

Clinical Basics

Subtype
CMTRIE

Classification
CMTRI

Neuropathy Type
Intermediate

Inheritance Pattern
autosomal recessive

Genetic Context

HGNC-Approved Gene Symbol
KCTD11

Gene Full Name
potassium channel tetramerization domain containing 11

HGNC Gene Alias(es)
C17ORF36

Chromosome
17p13.1

Zygosity of Responsible Variant
Homozygous or Compound Heterozygous

Variant Mechanism

Loss of Function (LoF)

Details

Mechanistic basis:
Complete loss

Confidence:
Medium

Prediction:
Mouse and cell data predict recessive loss in CMTRIE: KCTD11 serves as a substrate adaptor for the Cullin3 E3 ubiquitin ligase, and the recessive truncating and missense variants yield a protein cleared by autophagic degradation, so its substrates go un-ubiquitinated. A Kctd11-knockout mouse reproduces the myelin defect seen in patients, tying the phenotype to absence of the adaptor rather than to any activity of the mutant form.

Rationale:
Rapid degradation of the mutant adaptor is the decisive observation: the variant protein does not persist long enough to occupy Cullin3 or to act on the product of the other allele, leaving depletion as the operative lesion. The knockout mouse phenotype carries that argument further. Replication rests on a small number of families, holding the grade short of high.

ClinVar Pathogenic Variants

View KCTD11 ClinVar Variants

KCTD11 OMIM Entry

KCTD11 OMIM

More Info

CMTRIE Research Opportunity

CMT Natural History Study

Original Discovery Publication

Publication Title

Bi-allelic Mutations in KCTD11 Cause a New Form of Autosomal Recessive Intermediate Charcot-Marie-Tooth Disease

Authors

Gadacha, J., Haidar, Z., Roeckel-Trévisiol, N., Pauset, A., Castro, C., Provost, C., Hamzé, Z., Humbert, C., Bertaux, K., Lenfant, N., Masingue, M., de Becdelièvre, A., Konyukh, M., Bonello, N., Lia, A., Delmont, E., Bertini, A., Quartesan, I., Facchini, S., Cortese, A., Reilly, M.M., Houlden, H., Pareyson, D., Pisciotta, C., Attarian, S., Urtizberea, A., Mégarbané, A., Jabbour, R., Bernard-Marissal, N., Delague, V.

Publication Date
July 4, 2025

Updated: July 18, 2026 | By: K. Raymond

The Dorsal Root

More From The Dorsal Root


A Name That Does Too Much Work

Jean-Martin Charcot's name appears throughout medicine, but nowhere does it create more confusion than in the foot. Learn why the CMT foot and Charcot neuroarthropathy, also known as Charcot foot, share a name yet differ in how they develop, appear, and are managed.


When Medicine Lost Its Compass

Evidence failed not because it was wrong, but because it was weaponized. I lived the downstream effects of that failure for more than a decade. This is what happens when medicine forgets that data always ends in a human being.


Error 404: Gene Not Found

CMT genetic testing often fails to identify the cause of the disease, even when comprehensive panels are used. Here, we discuss why this happens, what genetic tests can and cannot do, and why a negative result still matters.