CMT-ABHD12

ABHD12 | 2010

What Is CMT-ABHD12?

CMT-ABHD12 is a type of CMT caused by autosomal recessive mutations in the ABHD12 gene. This gene provides instructions for making an enzyme that regulates lipid signaling molecules important to nervous system function. Mutations in the ABHD12 gene disrupt this function, leading to impaired nerve signal transmission.

CMT-ABHD12 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 CMT-ABHD12 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 slowed conduction velocities, consistent with a demyelinating form of CMT.

CMT-ABHD12 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

CMT-ABHD12 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
CMT-ABHD12

Classification
Unclassified Subtypes

Subtype Alias
PHARC

Neuropathy Type
Demyelinating

Inheritance Pattern
autosomal recessive

Genetic Context

HGNC-Approved Gene Symbol
ABHD12

Gene Full Name
Abhydrolase Domain Containing 12, Lysophospholipase

Chromosome
20p11.21

Zygosity of Responsible Variant
Homozygous or Compound Heterozygous

Variant Mechanism
Loss of Function (LoF)

ClinVar Pathogenic Variants

View CMT-ABHD12 ClinVar Variants

CMT-ABHD12 OMIM Entry

CMT-ABHD12 OMIM

ABHD12 OMIM Entry

ABHD12 OMIM

More Info

CMT-ABHD12 Research Opportunity

CMT Natural History Study

Original Discovery Publication

Publication Title

Mutations in ABHD12 Cause the Neurodegenerative Disease PHARC: An Inborn Error of Endocannabinoid Metabolism

Authors

Fiskerstrand, T., H’mida-Ben Brahim, D., Johansson, S., M’zahem, A., Haukanes, B. I., Drouot, N., Zimmermann, J., Cole, A. J., Vedeler, C., Bredrup, C., Assoum, M., Tazir, M., Klockgether, T., Hamri, A., Steen, V. M., Boman, H., Bindoff, L. A., Koenig, M., & Knappskog, P. M.

Publication Date
August 26, 2010

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

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