15 research outputs found
Twenty years on: Myoclonusâdystonia and Δâsarcoglycan â neurodevelopment, channel, and signaling dysfunction
Myoclonusâdystonia is a clinical syndrome characterized by a typical childhood onset of myoclonic jerks and dystonia involving the neck, trunk, and upper limbs. Psychiatric symptomatology, namely, alcohol dependence and phobic and obsessiveâcompulsive disorder, is also part of the clinical picture. Zonisamide has demonstrated effectiveness at reducing both myoclonus and dystonia, and deep brain stimulation seems to be an effective and longâlasting therapeutic option for medicationârefractory cases. In a subset of patients, myoclonusâdystonia is associated with pathogenic variants in the epsilonâsarcoglycan gene, located on chromosome 7q21, and up to now, more than 100 different pathogenic variants of the epsilonâsarcoglycan gene have been described. In a few families with a clinical phenotype resembling myoclonusâdystonia associated with distinct clinical features, variants have been identified in genes involved in novel pathways such as calcium channel regulation and neurodevelopment. Because of phenotypic similarities with epsilonâsarcoglycan geneârelated myoclonusâdystonia, these conditions can be collectively classified as âmyoclonusâdystonia syndromes.â In the present article, we present myoclonusâdystonia caused by epsilonâsarcoglycan gene mutations, with a focus on genetics and underlying disease mechanisms. Second, we review those conditions falling within the spectrum of myoclonusâdystonia syndromes, highlighting their genetic background and involved pathways. Finally, we critically discuss the normal and pathological function of the epsilonâsarcoglycan gene and its product, suggesting a role in the stabilization of the dopaminergic membrane via regulation of calcium homeostasis and in the neurodevelopmental process involving the cerebelloâthalamoâpallidoâcortical network