Juvenile Huntington’s disease

Abstract

Juvenile Huntingtons disease (JHD) manifests in 1st2nddecades of life and accounts for 29% of all cases ofHuntingtons disease; its pathogenic mechanisms are related togenetic anticipation and imprinting. Typical features of JHDare akinesia and rigidity, and paternal inheritance and huntingtinmutations with particularly large number of CAG repeats( 60); however, atypical cases exist, and maternal inheritanceis possible. We report 6 families with 7 JHD cases confirmed byDNA testing; 4 patients, including two brothers, were clinicallyexamined. Three patients, one of the brothers among them, hadan akinetic-rigid form with onset at 78 years; in the secondbrother the disease manifested at 20 years as a hyperkinetic formof the disease without dementia. This patient had mutation with57 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 thedisease manifested 45 years earlier than in the father, and inanother family grandfather first noticed symptoms at 60 years, 6years after the JHD onset in his granddaughter. Such casesmask dominant inheritance and complicate the diagnosis.Three families showed rare maternal transmission of JHD: oneof the affected mothers had JHD, and in two mothers the diseasedeveloped at 2730 years and lasted for 39 years. In 4clinically examined patients, JHD was supposed 718 yearsafter its onset which shows underestimation of the disease inpractice. JHD should be considered even in seemingly nonfamilialcases, and DNA testing for huntingtin mutationsshould be used more widely.

Keywords

• juvenile huntington’s disease
• huntingtin
• dna testing
• cag repeats
• anticipation
• clinical variability
• genetic counseling