CMTDIB

DNM2 | 2005

What Is CMTDIB?

CMTDIB is a type of CMT caused by autosomal dominant mutations in the DNM2 gene. This gene provides instructions for making dynamin-2, a protein involved in membrane trafficking and the maintenance of peripheral nerve structure. Mutations in the DNM2 gene disrupt this function, leading to impaired nerve signal transmission.

CMTDIB is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.

Clinical Features

The age of symptom onset in CMTDIB 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.

CMTDIB 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

CMTDIB 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
CMTDIB

Classification
CMTDI

Neuropathy Type
Intermediate

Inheritance Pattern
autosomal dominant

Genetic Context

HGNC-Approved Gene Symbol
DNM2

Gene Full Name
Dynamin 2

Chromosome
19p13.2

Zygosity of Responsible Variant
Heterozygous

Variant Mechanism
Toxic Gain of Function (GoF)

ClinVar Pathogenic Variants

View CMTDIB ClinVar Variants

CMTDIB OMIM Entry

CMTDIB OMIM

DNM2 OMIM Entry

DNM2 OMIM

More Info

CMTDIB Research Opportunity

CMT Natural History Study

Original Discovery Publication

Publication Title

Mutations in the Pleckstrin Homology Domain of Dynamin 2 Cause Dominant Intermediate Charcot-Marie-Tooth Disease

Authors

Züchner, S., Noureddine, M., Kennerson, M., Verhoeven, K., Claeys, K., De Jonghe, P., Merory, J., Oliveira, S. A., Speer, M. C., Stenger, J. E., Walizada, G., Zhu, D., Pericak-Vance, M. A., Nicholson, G., Timmerman, V., & Vance, J. M.

Publication Date
January 30, 2005

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

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