Table Of ContentJ uvenile Huntington’s
disease
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J uvenile
Huntington’s
disease
(and other trinucleotide
repeat disorders)
E dited by
O liver W. J. Quarrell
H elen M. Brewer
F erdinando Squitieri
R oger A. Barker
M artha A. Nance
G . Bernhard Landwehrmeyer
1
1
Great Clarendon Street, Oxford ox2 6dp
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D edication
This book is dedicated to all young people with juvenile Huntington’s
disease (JHD) and their families, especially those who have contributed
to this book or who were in the minds of the authors who contributed.
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P reface
W hy study juvenile Huntington’s disease?
J uvenile Huntington’s disease (JHD) is not a separate entity and, as will
be clear in this book, the definition of onset before the age of 20 years is
a convenience rather than a representation of a biological phenome-
non. JHD is a way of describing one end of the phenotypic spectrum of
HD. There have been studies, although few in number, focusing on
JHD; in addition, JHD is mentioned in books, book chapters, and other,
more general, studies of HD. Given this, why a book devoted to JHD?
T his project started following the formation of the European
Huntington’s Disease Network (EHDN). A number of working groups
were formed within the EHDN, one of which was on JHD. The working
group identified the need to gather information on this aspect of HD in
one place. To that end, an international meeting was convened in
London in November 2006; this formed the basis for the book. It does
mean that we have a starting point for clinicians who care for families
with the juvenile form of HD; in addition it should be a starting point
for researchers in identifying what is already known; more importantly,
this project has identified gaps in our knowledge.
C linicians interested in HD, laboratory based and social scientists,
together with members of the patients’ organizations form a commu-
nity. There has always been a close relationship between clinicians, sci-
entists and patients’ organizations, with meetings frequently involving
all of the above groups. This valuable working relationship is reflected
in this book, with the first two chapters being contributions from one
person with JHD and a number of parents/carers describing their per-
spective of the condition. Personal accounts of HD exist, but it is par-
ticularly useful to gather in one place accounts specifically about JHD.
Listening to, or reading, the experiences of patients and families is a
valuable method of extending knowledge and learning.
viii PREFACE
T he first few chapters focus on historical, clinical, and pathological
features of JHD. The next chapters have a more basic scientific nature.
It is important to realize that HD is part of a family of related disorders
characterized by an expansion of a CAG repeat sequence in the coding
part of the gene, so it is relevant to consider juvenile onset in these con-
ditions. The later chapters return to more clinical matters and areas for
future development, such as delays in reaching a diagnosis, psychoso-
cial issues, and problems with clinical rating scales.
I n recent years, much has been learnt from animal models of HD; the
overwhelming majority have very large expansions of the trinucleotide
CAG repeat mutation and can be said to be modelling the juvenile form
of the condition. We can anticipate future therapeutic interventions
being evaluated in these animal models. It is timely to draw together
information on those with young onset HD, many of whom also have
large trinucleotide repeat expansions. Currently, there are no evi-
denced-based guidelines for the management of JHD. JHD is relatively
rare, but with the use of web-based technology and international
research networks in Europe, North America, and elsewhere we can
start to address some of the gaps in our knowledge. The development of
reliable relevant rating scales is essential for including patients at the
young onset end of the phenotypic spectrum in intervention studies.
This is going to be crucial as and when we have treatments which poten-
tially alter the natural history of the condition. We need to be in a posi-
tion both to develop evidenced-based guidelines and to evaluate future
interventions for younger affected patients. Summarizing our current
knowledge of JHD in this book is one part of realizing that goal.
O liver W. J. Quarrell
Foreword: Juvenile
Huntington’s Disease
By Nancy S. Wexler, Ph.D.
Huntington’s disease is one of the most common Mendelian genetic
diseases in the world. Its prevalence includes those who are currently
symptomatic as well as those destined to develop symptoms in the
future. In Europe, Australia, New Zealand and the Americas, its preva-
lence is about 1 in 10,000 individuals who demonstrate symptoms at
any one time. But twice that number will become symptomatic in the
future.
In the European Union, Huntington’s disease affects approximately
150,000 to 200,000 individuals and in the U.S. about 100,000 people.
One-third of these people are individuals who currently have symp-
toms. The other two-thirds are carrying a copy of the expanded, abnor-
mal HD gene and will eventually, and inevitably, develop symptoms in
the future. Of all Huntington’s disease gene-carriers, about 10% will
develop symptoms after age 60 years old and about 10% will follow the
wrenching path of juvenile onset.
Everything aches in us when we see a child who is sick.
Children who suffer from juvenile Huntington’s disease are often the
exact opposite of their adult counterparts – even their parents. Instead
of the wild, flailing movements of all parts of the body, known as chorea,
children with juvenile Huntington’s disease are like tiny automatons,
rigid in all parts of their bodies. Their movements are stiff and slow –
like wooden puppets. Their eyes are dipped in glue. They can barely
move their pupils from side to side. And their facial expressions are
frozen in wax. Once they start to smile, it takes forever to fully bloom
and cover their faces. And then it slowly fades, like the Cheshire cat.
Even though some adults with Huntington’s disease develop symptoms
of rigidity and slowness, occasionally toward the end of their illness,
