Molecular genetics of infantile nervous system channelopathies

Gardiner, Mark

doi:10.1016/j.earlhumdev.2006.09.013

« Previous Next »Early Human Development
Volume 82, Issue 12 , Pages 775-779, December 2006

Molecular genetics of infantile nervous system channelopathies

Royal Free and University College Medical School, University College London, Institute of Child Health, Department of Paediatrics and Child Health, The Rayne Building, 5 University Street, London, WC1E 6JJ, United Kingdom

Abstract

Inherited or de novo mutations in at least a dozen genes encoding ion channels may present as paroxysmal disorders during the neonatal period or first year of life.

These channelopathies include genes encoding voltage-gated channels specific for sodium (SCN1A, SCN2A, SCN1B, SCN9A) and potassium (KCNQ2, KCNQ3) which account for a variety of epilepsy phenotypes ranging from mild, such as Benign familial neonatal seizures (BFNS) to severe, such as Dravet syndrome (severe myoclonic epilepsy of infancy, SMEI) and the rare and unusual syndrome paroxysmal extreme pain disorder (PEPD).

Ligand-gated channels involved include the GABA_A receptor in a variety of epilepsy phenotypes and the human glycine receptor. Mutations in five genes encoding subunits of this receptor and accessory molecules underlie hyperekplexia or stiff-baby syndrome.

All these conditions are rare but correct diagnosis is of value not only for genetic counselling but to allow the specific treatment which is available.

KEYWORDS: Epilepsy;, Ion channels;, Channelopathy;, Neonatal