Hereditary Myelopathies

Continuum (Minneap Minn). 2018 Apr;24(2, Spinal Cord Disorders):523-550. doi: 10.1212/CON.0000000000000580.


Purpose of review: Hereditary myelopathies are very diverse genetic disorders, and many of them represent a widespread neurodegenerative process rather than isolated spinal cord dysfunction. This article reviews various types of inherited myelopathies, with emphasis on hereditary spastic paraplegias and spastic ataxias.

Recent findings: The ever-growing number of myelopathy-causing genes and broadening of phenotype-genotype correlations makes the molecular diagnosis of inherited myelopathies a daunting task. This article emphasizes the main phenotypic clusters among inherited myelopathies that can facilitate the diagnostic process. This article focuses on newly identified genetic causes and the most important identifying clinical features that can aid the diagnosis, including the presence of a characteristic age of onset and additional neurologic signs such as leukodystrophy, thin corpus callosum, or amyotrophy.

Summary: The exclusion of potentially treatable causes of myelopathy remains the most important diagnostic step. Syndromic diagnosis can be supported by molecular diagnosis, but the genetic diagnosis at present does not change the management. Moreover, a negative genetic test does not exclude the diagnosis of a hereditary myelopathy because comprehensive molecular testing is not yet available, and many disease-causing genes remain unknown.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Genetic Testing
  • Humans
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Muscle Spasticity / diagnosis
  • Muscle Spasticity / genetics*
  • Muscle Spasticity / pathology
  • Optic Atrophy / diagnosis
  • Optic Atrophy / genetics*
  • Optic Atrophy / pathology
  • Spastic Paraplegia, Hereditary / diagnosis
  • Spastic Paraplegia, Hereditary / genetics*
  • Spastic Paraplegia, Hereditary / pathology
  • Spinal Cord / pathology
  • Spinal Cord Diseases / diagnosis
  • Spinal Cord Diseases / genetics*
  • Spinal Cord Diseases / pathology
  • Spinal Neoplasms / diagnosis
  • Spinal Neoplasms / genetics*
  • Spinocerebellar Ataxias / diagnosis
  • Spinocerebellar Ataxias / genetics*
  • Spinocerebellar Ataxias / pathology

Supplementary concepts

  • Spastic Ataxia