Clinical Information

Huntington disease (HD) is an autosomal dominant progressive neurodegenerative disorder associated with progressive involuntary and voluntary motor disturbances (chorea, dystonia, dysarthria, gait disturbance, postural instability, oculomotor dysfunction), cognitive decline leading to dementia, and a wide range of neuropsychiatric problems including apathy, depression, anxiety, and other behavioral disturbances. Onset occurs typically in the late 30's to early 40's, but rare individuals may present with juvenile onset.

Huntington disease is caused by a CAG (cystine, adenine, guanine) repeat expansion in the HTT gene and is associated with genetic anticipation, whereby repeat sizes may expand with transmission to subsequent generations. Correlation exists between the size of the CAG repeat and disease onset and severity, with larger alleles associated with earlier onset and more severe disease presentation. Full penetrance HTT expansions are greater than 39 repeats, while normal alleles are less than 27 repeats. Allele sizes between 36 and 39 repeats are associated with reduced penetrance of clinical HD symptoms. Intermediate alleles (27-35 repeats) are not typically associated with clinical symptoms; however, both reduced penetrance and intermediate alleles may expand into the full penetrance range with transmission to offspring.

Identification of a disease-associated repeat expansion has important implications for family members. Testing of at-risk individuals is possible, but it is recommended that predictive testing be performed in conjunction with appropriate pre- and post-test counseling. Additionally, presymptomatic testing of minors is strongly discouraged.