Genetics of Common Neurologic Diseases

Our understanding of the genetics of neurologic disorders is evolving rapidly. Genetic neurologic disorders are no longer simply the Mendelian disorders with obvious patterns of inheritance; or collections of rare metabolic and degenerative syndromes that are the purview of specialists alone. Rather, it is increasingly clear that genetic factors contribute to virtually every neurologic disorder, from stroke to seizure; from dementia to degenerative disk disease.

This generalization is based on analysis of even the most “etiologically simple” disorders (e.g., neurotrauma), which upon closer inspection, represent the complex interplay between inciting pathogens, compensatory and exacerbating responses, and restorative processes. In some instances, genetic variations are pathogenic, either directly or through gene-environment interaction. In other instances, genetic variations may influence the disease phenotype not as pathogens, but rather by modifying compensatory responses to nervous system injury or the capacities for neuroplasticity and recovery. Finally, genetic variations may influence the response to treatment.

This issue of Seminars in Neurology discusses the role of genetic factors involved in some of the most common neurologic disorders: headache, stroke, sleep disorders, Parkinson's disease, degenerative disk disease, vertigo, and dementia. Together, these disorders represent more than half of out-patient neurologic practice. Recognizing genetic syndromes among these common neurologic disorders has important implications for clinical care and counseling of these patients and their families. Moreover, recognizing the role of genetic factors in these disorders provides insight into their pathophysiology and deepens our awareness of individual variation in the manifestations of disease. This is an essential first step in a pharmacogenomic approach to developing individualized treatments for these common neurologic conditions.

I am grateful to Dr. Karen Roos for the opportunity to edit this volume; and to the contributing authors who have provided valuable, thought provoking, and lucid reviews.