CMT-SCYL1

SCYL1 | 2015

What Is CMT-SCYL1?

CMT-SCYL1 is a type of CMT caused by autosomal recessive mutations in the SCYL1 gene. This gene provides instructions for making a protein involved in the transport of materials within nerve cells. Mutations in the SCYL1 gene disrupt this function, leading to impaired nerve signal transmission.

CMT-SCYL1 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-SCYL1 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.

CMT-SCYL1 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-SCYL1 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-SCYL1

Classification
Unclassified Subtypes

Neuropathy Type
Axonal

Inheritance Pattern
autosomal recessive

Genetic Context

HGNC-Approved Gene Symbol
SCYL1

Gene Full Name
Scy1 Like Pseudokinase 1

HGNC Gene Alias(es)
NTKL

Chromosome
11q13.1

Zygosity of Responsible Variant
Homozygous

Variant Mechanism
Loss of Function (LoF)

ClinVar Pathogenic Variants

View CMT-SCYL1 ClinVar Variants

SCYL1 OMIM Entry

SCYL1 OMIM

More Info

CMT-SCYL1 Research Opportunity

CMT Natural History Study

Original Discovery Publication

Publication Title

Disruptive SCYL1 Mutations Underlie a Syndrome Characterized by Recurrent Episodes of Liver Failure, Peripheral Neuropathy, Cerebellar Atrophy, and Ataxia

Authors

Schmidt, W. M., Rutledge, S. L., Schüle, R., Mayerhofer, B., Züchner, S., Boltshauser, E., & Bittner, R. E.

Publication Date
December 3, 2015

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

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