Neurogenetics and genetic and genomic testing

Jacinda B Sampson MD PhD (Dr. Sampson of Stanford University is a co-investigator for clinical trials sponsored by Bristol Meyers Squibb, PTC Therapeutics, and Sarepta.)
Jill Goldman MS MPhil CGC (Jill Goldman of Columbia University Medical School has no relevant financial relationships to disclose.)
Sarah Teed (Sarah Teed of Memorial Sloan Kettering Hospital has no relevant financial relationships to disclose.)
Emma Ciafaloni MD, editor. (

Dr. Ciafaloni of the University of Rochester received consulting fees from Biogen and Pfeizer and research grants from Sarepta and Santhera.

Originally released September 27, 2013; last updated January 15, 2018; expires January 15, 2021


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 (Alonso-Fernandez and Colon 2009)



Episodic neurologic symptoms-including seizure

Avoidance of precipitating medications (Granick 1966)


Wilson disease

Neurodegeneration, liver failure

Chelation therapy (Walshe 1973)


Metachromatic leukodystrophy

Cognitive decline, neuropathy

Bone marrow transplant (Bayever and Ladisch 1985)


Duchenne muscular dystrophy

Delay, loss of ambulation

Corticosteroids (Karpati and Acsadi 1994)


Fabry disease

Recurrent stroke

Enzyme replacement (Schiffmann et al 2001)


Pompe disease

Respiratory failure from muscular dystrophy

Enzyme replacement (Amalfitano et al 2001)


Friedreich ataxia


Idebenone (Hausse et al 2002)


Nonsense-mediated Duchenne muscular dystrophy

Slow decline in walking speed

Ataluren (Bushby et al 2014; Haas et al 2015)


Exon 51-skip amenable Duchenne muscular dystrophy

Increased dystrophin expression



Spinal muscular atrophy


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