Genetic neurological channelopathies: molecular genetics and clinical phenotypes

Abstract

Evidence accumulated over recent years has shown that genetic neurological channelopathies can cause many different neurological diseases. Presentations relating to the brain, spinal cord, peripheral nerve or muscle mean that channelopathies can impact on almost any area of neurological practice. Typically, neurological channelopathies are inherited in an autosomal dominant fashion and cause paroxysmal disturbances of neurological function, although the impairment of function can become fixed with time. These disorders are individually rare, but an accurate diagnosis is important as it has genetic counselling and often treatment implications. Furthermore, the study of less common ion channel mutation-related diseases has increased our understanding of pathomechanisms that is relevant to common neurological diseases such as migraine and epilepsy. Here, we review the molecular genetic and clinical features of inherited neurological channelopathies.

Keywords: CHANNELS; GENETICS; MOLECULAR BIOLOGY.

Figure 1

(A) Structure of the α subunit of the voltage-gated sodium channel Na_V1.1 encoded by SCN1A. The subunit is composed of four domains (I–IV), which are each composed of six transmembrane subunits (S1–S6)—the positive gating charges in the S4 subunit are marked as is the pore region (between S5 and S6). (B) Schematic representation of ion channel in open and closed states.