Rare Neurodegenerative Diseases: Clinical and Genetic Update

Adv Exp Med Biol. 2017:1031:443-496. doi: 10.1007/978-3-319-67144-4_25.


More than 600 human disorders afflict the nervous system. Of these, neurodegenerative diseases are usually characterised by onset in late adulthood, progressive clinical course, and neuronal loss with regional specificity in the central nervous system. They include Alzheimer's disease and other less frequent dementias, brain cancer, degenerative nerve diseases, encephalitis, epilepsy, genetic brain disorders, head and brain malformations, hydrocephalus, stroke, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS or Lou Gehrig's Disease), Huntington's disease, and Prion diseases, among others. Neurodegeneration usually affects, but is not limited to, the cerebral cortex, intracranial white matter, basal ganglia, thalamus, hypothalamus, brain stem, and cerebellum. Although the majority of neurodegenerative diseases are sporadic, Mendelian inheritance is well documented. Intriguingly, the clinical presentations and neuropathological findings in inherited neurodegenerative forms are often indistinguishable from those of sporadic cases, suggesting that converging genomic signatures and pathophysiologic mechanisms underlie both hereditary and sporadic neurodegenerative diseases. Unfortunately, effective therapies for these diseases are scarce to non-existent. In this chapter, we highlight the clinical and genetic features associated with the rare inherited forms of neurodegenerative diseases, including ataxias, multiple system atrophy, spastic paraplegias, Parkinson's disease, dementias, motor neuron diseases, and rare metabolic disorders.

Keywords: Ataxia; Dementia; Genetic diagnosis; Metabolic disorders; Movement disorders; Neuromuscular.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • DNA Mutational Analysis
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genomics / methods*
  • Heredity
  • Humans
  • Mutation*
  • Neurodegenerative Diseases / diagnosis
  • Neurodegenerative Diseases / epidemiology
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / therapy
  • Phenotype
  • Predictive Value of Tests
  • Prognosis
  • Rare Diseases / diagnosis
  • Rare Diseases / epidemiology
  • Rare Diseases / genetics*
  • Rare Diseases / therapy
  • Risk Factors


  • Genetic Markers