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  • Updated 10.07.2019
  • Released 09.27.2013
  • Expires For CME 10.07.2022

Neurogenetics and genetic and genomic testing



Neurogenetics encompasses heritable disorders in all the subspecialties of neurology and is an ever-growing field. New technologies such as next-generation sequencing (including whole exome or whole genome sequencing) are expanding testing options, discovering new mutations, and creating challenges in counseling, interpreting, and reporting results to the patient. Yet, next-generation sequencing does not detect many neurogenetic disorders. This article summarizes the types of genetic tests currently available and the resources for choosing appropriate and economical testing are discussed.

Key points

• Deciding on the genetic tests to order can be simplified by narrowing the differential diagnosis and defining the patient’s phenotype.

• Next-generation sequencing of the whole exome is useful for testing for multiple candidate genes simultaneously or for discovering new, rare disorders.

• Whole exome sequencing is not suitable for detecting polynucleotide repeat disorders or large insertion/deletions.

• Genetic counseling, informed consent, and insurance preauthorization must be obtained before performing genetic testing.

Historical note and terminology

Genetic disorders affecting the nervous system typically present first to the general neurologist at any point in the patient’s lifespan. Neurogenetic disorders are a component of every neurologic subspecialty. The heritable nature of certain neurogenetic disorders was appreciated well before the discovery of DNA. Diagnosis by biochemical assays for metabolic and enzymatic defects, or histologic changes on muscle biopsy well preceded the description of DNA. Indeed, the precedent for treatment of neurogenetic disorders with metabolic defects began before clinical genetic tests became available.

Table 1. Timeline of Therapies of Neurogenetic Disorders

Year therapy






Cognitive decline

Dietary restriction, phenylalanine (02)



Episodic neurologic symptoms-including seizure, neuropathy

Avoidance of precipitating medications (17)


Wilson disease

Neurodegeneration, liver failure

Chelation therapy (41)


Metachromatic leukodystrophy

Cognitive decline, neuropathy

Bone marrow transplant (Bayever and Ladisch 1985)


Duchenne muscular dystrophy

Muscle degeneration, cardiomyopathy

Corticosteroids (25)


Fabry disease

Stroke, cardiomyopathy, renal failure

Enzyme replacement (36)


Pompe disease

Respiratory failure from muscular dystrophy

Enzyme replacement (03)


Nonsense-mediated Duchenne muscular dystrophy

Slow decline in walking speed

Ataluren (09; 21)


Exon 51-skip amenable Duchenne muscular dystrophy

Increased dystrophin expression

ExonDys51 (28)


Spinal muscular atrophy

Increased survival motor neuron (SMN) expression

Nusinersen (16)

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