dHMN-VWA1

VWA1 | 2021

What Is dHMN-VWA1?

dHMN-VWA1 is a type of CMT caused by autosomal recessive mutations in the VWA1 gene. This gene provides instructions for making a protein of the extracellular matrix that supports the structure surrounding motor nerve cells. Mutations in the VWA1 gene disrupt this function, leading to impaired nerve signal transmission.

dHMN-VWA1 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 dHMN-VWA1 is variable, ranging from childhood to adulthood. As a motor neuropathy, dHMN-VWA1 primarily affects the most distal points, with weakness and atrophy of the feet and hands, and little to no involvement of the sensory nerves. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT.

dHMN-VWA1 symptoms may include:

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

Disease Course

dHMN-VWA1 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
dHMN-VWA1

Classification
dHMN/HMN

Neuropathy Type
Axonal

Inheritance Pattern
autosomal recessive

Genetic Context

HGNC-Approved Gene Symbol
VWA1

Gene Full Name
Von Willebrand Factor a Domain Containing 1

HGNC Gene Alias(es)
WARP

Chromosome
1p36.33

Zygosity of Responsible Variant
Homozygous or Compound Heterozygous

Variant Mechanism
Loss of Function (LoF)

ClinVar Pathogenic Variants

View dHMN-VWA1 ClinVar Variants

dHMN-VWA1 OMIM Entry

dHMN-VWA1 OMIM

VWA1 OMIM Entry

VWA1 OMIM

More Info

dHMN-VWA1 Research Opportunity

CMT Natural History Study

Original Discovery Publication

Publication Title

An Ancestral 10-bp Repeat Expansion in VWA1 Causes Recessive Hereditary Motor Neuropathy

Authors

Pagnamenta, A. T., Kaiyrzhanov, R., Zou, Y., Da’as, S. I., Maroofian, R., Donkervoort, S., Dominik, N., Lauffer, M., Ferla, M. P., Orioli, A., Giess, A., Tucci, A., Beetz, C., Sedghi, M., Ansari, B., Barresi, R., Basiri, K., Cortese, A., Elgar, G., Fernandez-Garcia, M. A., … Houlden, H.

Publication Date
January 18, 2021

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

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