Unravelling the mysteries of juvenile Huntington's disease

Abstract

Huntington's disease (HD) is one of the most common autosomal dominant disorders worldwide and one of the most devastating neurological diseases. The prevalence of HD is about 1 in 10 000 and it affects about 200 000 individuals in the Europe and about 100 000 in the USA. The symptoms of HD can start at any age, but usually appear after the age of 40 years. The disease is called juvenile HD when it starts before the age of 20 years. HD with onset under 10 years of age is indeed quite rare, probably representing no more than 0·5% of all patients with HD. This disorder is even more distressing when it affects children, both because of the inherent effect on the parents' lives and because the early-onset form has more severe and rapidly progressive symptoms than the adult-onset form, and the disease might not be promptly recognised owing to lack of experience in most centres. In fact, HD in children is a completely different clinical disorder, which is mostly explained by larger expansions of trinucleotide CAG repeats (usually larger than 80 CAGs)—which was known clinically as “anticipation” long before the identification of the causative gene and the current understanding of the molecular mechanisms underlying CAG repeat disorders. Overall, this book edited by Quarrell and colleagues is a concise yet comprehensive, updated, and well-referenced review of all the relevant aspects of juvenile HD, which are hard to find elsewhere. The editors did a great job in assembling this book. The first two chapters provide an excellent description of the experiences of families whose lives “have been so irrevocably and relentlessly altered by juvenile HD”. These experiences are not easy matters to talk or think about; however, the text is useful in helping others understand what families go through with this distressing disorder. The following chapters review the history of juvenile HD, discuss its pathology, biochemistry, and molecular mechanisms, and outline the role of mutation instability, animal models, clinical findings, and management of the disease. There is also a chapter about the clinical features of early and juvenile onset of other polyglutamine disorders, including autosomal dominant ataxias (eg, spinocerebellar ataxia) and dentatorubral-pallidoluysian atrophy. The book concludes with psychosocial factors and appendices with proposed scales for juvenile HD, which are adequately discussed and are very useful for researchers, clinicians, and health-care professionals. As noted in the foreword of the book, “despite the number of people worldwide with HD, finding health-care professionals who understand the profound complexities of treating HD is extremely difficult”, and finding experts on the less common and more complicated form of juvenile HD “is impossible in many parts of the world”. For this reason, this book is important for health-care professionals who specialise in these neurological disorders. The text provides an excellent reference for all aspects of HD and the most common trinucleotide repeat disorders, and is recommended for neurologists, movement disorders specialists, paediatricians, geneticists, and students, as well as for caregivers of individuals with HD.