Juvenile Huntington’s disease

Juvenile Huntington’s disease (JHD) manifests in 1st–2nd decades of life and accounts for 2–9% of all cases of Huntington’s disease; its pathogenic mechanisms are related to genetic anticipation and imprinting. Typical features of JHD are akinesia and rigidity, and paternal inheritance and huntingtin mutations with particularly large number of CAG repeats (> 60); however, atypical cases exist, and maternal inheritance is possible. We report 6 families with 7 JHD cases confirmed by DNA testing; 4 patients, including two brothers, were clinicallyexamined. Three patients, one of the brothers among them, had an akinetic-rigid form with onset at 7–8 years; in the second brother the disease manifested at 20 years as a hyperkinetic form of the disease without dementia. This patient had mutation with 57 CAG repeats, while in the rest six patients the number ofrepeat copies varied from 63 to 81. All cases were familial, and anticipation in families was evident; in one child with JHD the disease manifested 4–5 years earlier than in the father, and in another family grandfather first noticed symptoms at 60 years, 6years after the JHD onset in his granddaughter. Such cases mask’ dominant inheritance and complicate the diagnosis. Three families showed rare maternal transmission of JHD: one of the affected mothers had JHD, and in two mothers the disease developed at 27–30 years and lasted for 3–9 years. In 4 clinically examined patients, JHD was supposed 7–18 years after its onset which shows underestimation of the disease in practice. JHD should be considered even in seemingly nonfamilial cases, and DNA testing for huntingtin mutations should be used more widely.