Phenotypic variability in huntington's disease

Identification of such candidate genes, which act as a genetic modifier in the pathogenesis of HD, will allow for the development of treatment options that can modulate the disease process and, thus, delay or prevent the symptom onset in the individuals carrying mHTT gene. The triad of chorea, cognitive and neuropsychiatric disturbance is considered to be the characteristic of HD, but in the absence of HTT gene mutation, one should consider HD phenocopies as alternative diagnosis including Huntington disease like 2 (HDL-2) and dentatorubral pallidoluysian atrophy, spino-cerebellar ataxia (types 2, 3, 12 and 17), neuroacanthocytosis and C9orf72 expansions. The most promising disease-modifying approaches that are under trial include therapies aimed at lowering levels of mHTT by targeting either the DNA or RNA of the mHTT gene using anti-sense oligonucleotides (ASOs), RNA interference (RNAi) or small molecule splicing inhibitors.