HMSN-5

2008

What Is HMSN-5?

HMSN-5 is a type of CMT with an established locus but no confirmed causative gene identified to date. It follows an autosomal dominant inheritance pattern.

For HMSN-5, genetic evidence supports an autosomal dominant inheritance pattern, 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 HMSN-5 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 and reduced amplitudes, consistent with an axonal form of CMT.

HMSN-5 symptoms may include:

  • Weakness in the feet and lower legs
  • Muscle atrophy
  • Foot drop
  • Brisk 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

HMSN-5 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
HMSN-5

Classification
HMSN

Neuropathy Type
Axonal

Inheritance Pattern
autosomal dominant

Genetic Context

HGNC-Approved Gene Symbol
Gene is Unknown at This Time

Chromosome
4q34.3-q35.2

Zygosity of Responsible Variant
Heterozygous

Variant Mechanism

Unknown

Details

Mechanistic basis:
Gene unknown

Confidence:
High

Prediction:
HMSN-5 is a phenotype label rather than a genetic entity: the historical HMSN classification used it for CMT accompanied by pyramidal signs, and families answering that description have turned out to be genetically heterogeneous, with pyramidal involvement arising in more than one dominant disease. No single gene attaches to the designation, so the literature supports no mechanism for it as a unit.

Rationale:
Heterogeneity, not an unmapped locus, is what blocks a mechanism here. The designation collects diseases that share a clinical picture and differ in cause, so any allele class named for the group would in fact belong to one of its members, and nothing generalizes to HMSN-5 itself.

HMSN-5 OMIM Entry

HMSN-5 OMIM

More Info

HMSN-5 Research Opportunity

CMT Natural History Study

Original Discovery Publication

Publication Title

A Novel Locus for dHMN with Pyramidal Features Maps to Chromosome 4q34.3-q35.2

Authors

Muglia, M., Magariello, A., Citrigno, L., Passamonti, L., Sprovieri, T., Conforti, F. L., Mazzei, R., Patitucci, A., Gabriele, A. L., Ungaro, C., Bellesi, M., & Quattrone, A.

Publication Date
April 7, 2008

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

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