Patients with highly expanded (HE) juvenile Huntington disease (characterized by 80 or more repeats) differ significantly in their clinical presentation compared with patients with low expansion (LE, median of about 60 repeats), and adult-onset Huntington disease. These differences suggest a new classification may be valuable for the understanding of this particularly aggressive form of the disease, according to a study published in The Lancet Neurology.
This study aimed to gather data on the clinical characteristics of juvenile Huntington disease and to examine the effect of CAG repeat size on disease presentation, progression, and survival. Researchers performed a retrospective review of patients from several international databases for patients with Huntington disease.
Researchers examined medical records for 580 patients, gathering data on neurological, behavioral, and nonmotor symptoms, including those uncommon in adult-onset Huntington disease. Cross-sectional data from disease onset was collected, as well as longitudinal data regarding disease progression. After reassessing CAG mutation information, researchers classified patients as HE or LE.
Study investigators compared symptoms at onset and during disease progression for both subgroups. Longitudinal progression of the disease was evaluated using the longitudinal change in Total Motor Score measured by the Unified Huntington’s Disease Rating Scale.
Researchers found significant differences in the presenting symptoms of the two subgroups. For the HE patients, the most common initial symptom was gait disturbances (8 of 10 patients [80%]), and this differed from the LE subgroup’s data (7 of 26 patients [27%]; P =.0071). The most common initial symptom for the LE subgroup was loss of hand dexterity (11 of 26 patients [42%]), whereas no patients in the HE group experienced this as an initial presenting symptom (0 of 10 patients [0%]; P=.0160). Other marked differences were 0% development delay for patients in the LE subgroup vs 90% in the HE subgroup (P <.0001). Disease progression occurred more rapidly in juvenile Huntington disease (n=14) than in adult-onset Huntington disease (n=52; generalized estimating equation model, P =.0003). Other findings included reduced survival for juvenile patients and brain abnormalities not previously described in adult-onset Huntington disease.
Limitations for the study include small sample size, the retrospective nature of the data, and differences in pathophysiology for juvenile vs adult patients. The authors conclude that CAG length can translate into different disease presentations and different rates of progression. This result suggests that a reclassification of juvenile Huntington disease is warranted to account for the differences in clinical and biological manifestations of the disease.
Multiple authors declare associations with the pharmaceutical industry. Please see original reference for a full list of authors’ disclosures.
Fusilli C, Migliore S, Mazza T, et al. Biological and clinical manifestations of juvenile Huntington’s disease: a retrospective analysis [published online September 19, 2018]. Lancet Neurol. doi: 10.1016/S1474-4422(18)30294-1