Huntington Disease: Neurogenomic Trajectories & Care Innovations
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG trinucleotide expansion in the HTT gene. This dossier explores genotype-phenotype correlations, neuroimaging biomarkers, and emerging gene modulation therapies.
Global Prevalence
2.7 / 100K
Higher clusters in Western Europe, North America, South Africa
CAG Range
36–70+
Pathogenic expansions with juvenile onset >60 repeats
Clinical Trials
38 Active
Gene-silencing, small molecules, neuromodulation
Genomic Insights
Allele size influences age of onset. Reduced penetrance alleles (36-39 repeats) require nuanced counseling, while anticipation remains prominent in paternal transmission.
- • Triplet repeat primed PCR recommended for screening.
- • Haplotyping data informs ancestry-specific risk models.
- • Somatic instability metrics linked with disease progression.
Therapeutic Innovations
Gene Silencing Modalities
Tominersen (antisense oligonucleotide) undergoes optimized dosing regimens, while allele-selective ASOs target mutant HTT transcripts with minimal wild-type impact.
Cell & Neurotrophic Therapies
iPSC-derived neural progenitors, MSC infusions, and BDNF delivery vectors show early safety signals in multinational trials.
Integrated Care Approaches
Interdisciplinary HD clinics combine neurologists, genetic counselors, psychologists, and occupational therapists. Tele-neurology extends services to rural families.
- • Wearable tech for motor assessment (UHDI initiative).
- • Cognitive training and speech therapy integration.
- • Advance care planning with culturally tailored frameworks.