Practical Genetic Counseling, 7th Edition

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First published in Great Britain in 1981 by John Wright Ltd
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Third edition 1988
Reprinted 1991
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Contents
Preface vii
Acknowledgements viii

PART I General Aspects of Genetic Counselling

1. Genetic Counselling: an Introduction 3
2. Genetic Counselling in Mendelian Disorders 23
3. Common Disorders and Genetic Counselling 54
4. Chromosome Abnormalities 63
5. Molecular Genetics and Genetic Counselling 81
6. Dysmorphology and Genetic Syndromes 91
7. Carrier Testing and Genetic Prediction 102
8. Prenatal Diagnosis and Reproductive Aspects of Medical Genetics 115
9. Special Issues in Genetic Counselling 135
10. The Genetic Counselling Clinic 150

Part II Genetic Counselling: Specific Organ Systems

11. Neuromuscular Disorders 167
12. Central Nervous System Disorders 179
13. Disorders of Mental Function 201
14. Disorders of Bone and Connective Tissue 216
15. Oral and Craniofacial Disorders 234
16. The Skin 242
17. The Eye 253
18. Deafness 265
19. Cardiovascular and Respiratory Disorders 271
20. The Gastrointestinal Tract 287
21. Renal and Urinary Tract Disease 297
22. Endocrine and Reproductive Disorders 305
23. Inborn Errors of Metabolism 317
24. Disorders of Blood and Immune Function 325
25. Genetic Risks in Cancer 334
26. Environmental Hazards 348

Part III Genetic Counselling: the Wider Picture

27. Population Aspects of Genetic Counselling and Genetic Screening 361
28. Genetics and Society 375

Appendix: Useful Information in Connection with Genetic Counselling 385

Glossary 389
Index 395
 To
Elaine
and to
Matthew
Emma Jane
Nicholas
Katy Thi
Lucy
and
Osiris
Preface
This seventh edition of Practical Genetic Counselling is also the final one, at least in its
present form. Most of the book’s value over the years has come from it reflecting the
experience of someone directly involved in genetic counselling and its problems. Since I
am no longer in active clinical practice, it seems best to let this final edition stand for
what I consider to be the main foundations of present-day genetic counselling, rather
than attempt myself to continue it into the future.
It is now 30 years since I wrote the first edition of the book, and more than 40 years
since I began to practice Medical Genetics. During this time it has been truly amazing
to see what has altered in terms of what we are able to do. Looking back, it seems almost
unbelievable that when I started in the field there was no prenatal diagnosis, almost no
carrier detection, let alone presymptomatic testing, while human molecular genetics
was non-existent, as were its practical applications of mutation detection and linked
DNA markers.
At another level, though, much has remained unchanged. The problems and ques-
tions that families bring to us are largely the same, and so are the main approaches used
in genetic counselling to try to help them. New laboratory advances have greatly
extended what we are able to do, but have not removed the need for the practice of
genetic counselling, and of clinical genetics generally, to rest on these long established
foundations, and on sound psychological principles for the way in which we interact
with those we see.
I wrote the original edition of this book primarily for those who were not experts or
specialists in the field, and have been surprised to find that those working in Medical
Genetics have also found it useful, particularly trainees and, increasingly, non-medical
genetic counsellors. I suspect that this is because the book is short and written in simple
language, and has never attempted to provide the details that can be found in larger
volumes.
One final aspect that has brought me particular pleasure has been the book’s wide
use, often in translation, across the world, including countries where previously genetic
counselling was non-existent or very different in its approaches. I have often felt
humbled by the appreciation that people from such countries have shown to me and I
hope that, in turn, Practical Genetic Counselling has made a contribution to forging
even closer links between members of the international community of workers in the
field.

Peter Harper, Cardiff, February 2010

Acknowledgements
As with previous editions, I owe a great debt to my Cardiff colleagues, who have
provided suggestions and comments and especially to Angus Clarke, who has contrib-
uted greatly to the ‘Further reading’ given at the end of each chapter. Selwyn Roberts
has again helped with cytogenetic advice and Buddug Williams with web information.
A number of people have sent me helpful suggestions and corrections and I feel par-
ticularly honoured to have received detailed comments from Dr F. Clarke Fraser, one of
the pioneers of Medical Genetics.
The publishers, Hodder Arnold, have been unfailingly helpful and efficient in seeing
this volume through to its final form, as has Oxford University Press in the United
States, while I am most grateful to Joanne Richards for her help in reorganizing the text
and preparing it for publication.
 PA R T I

General Aspects
of Genetic Counselling
This page intentionally left blank
CH A P T ER 1

Genetic Counselling: an Introduction

What do we mean by ‘genetic counselling’? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

The history and development of genetic counselling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Constructing a family tree . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Diagnostic information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Genetic risk estimation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
The basis of risk estimation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Communication and genetic counselling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
The back-up to genetic counselling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Support in the context of genetic counselling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Further reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

WHAT DO WE MEAN BY ‘GENETIC COUNSELLING’?

Although most people working in the field of medicine are familiar with the term
‘genetic counselling’ and have some idea what it means, it is surprisingly rare to see it
actually defined. Closer enquiry among patients and colleagues shows a wide variation
in people’s concepts of what the process of genetic counselling actually entails. Some
envisage an essentially supportive – even psychotherapeutic – role, akin to that of coun-
selling processes in the social field; others see genetic counselling as primarily
concerned with special diagnostic tests in inherited disease; yet others regard it as a
complex mathematical process involving the estimation of risk.
All these views of genetic counselling contain a considerable element of truth, but
none fully identifies what the overall process of genetic counselling actually involves.
Even within the group of professionals for whom genetic counselling is a major activity,
there are varied opinions as to its proper role and scope, but in essence it is a composite
activity, made up of a series of key elements that individually are very different, but which
together constitute a process that is highly distinctive in its character and its ethos.
Previous editions of this book have given various definitions of genetic counselling,
but all of them are cumbersome and unsatisfactory. It is more meaningful to list here
the principal elements of genetic counselling, and these are given in Box 1.1.
This chapter outlines these main elements, which are then dealt with in more detail
in subsequent chapters of the book. It is the satisfactory synthesis of these various aspects
that makes up genetic counselling as a specific process. A thoughtful and valuable dis-
cussion of the process of genetic counselling is given by Clarke (see ‘Further reading’).
4 Practical Genetic Counselling

Box 1.1 Genetic counselling: the main elements

Diagnostic and clinical aspects

Documentation of family and pedigree information
Recognition of inheritance patterns and risk estimation
Communication and empathy with those seen
Information on available options and further measures
Support in decision-making and for decisions made

THE HISTORY AND DEVELOPMENT OF GENETIC

COUNSELLING
The origins of genetic counselling need to be seen within the context of the overall
history of human genetics, a topic until recently neglected, but which is given by
McKusick’s introductory chapter for Emery and Rimoin’s textbook and more recently
in my own Short History of Medical Genetics (see ‘Further Reading’).
Although human genetics research had begun to develop strongly in the first half of
the twentieth century, its application at that time was confused and, to an extent, dis-
credited by the abuses of eugenics. It was not until the Second World War that the first
genetic counselling clinics were opened in America, in Michigan in 1940 and in
Minnesota in 1941. In the UK, the Hospital for Sick Children in Great Ormond Street,
London, developed the first such clinic in 1946. By 1955 there were over a dozen centres
in North America and there has been a steady development since that time. As with
many pioneering developments, the early centres were often the work of far-sighted
eccentrics. Sheldon Reed, in his book Counselling in Medical Genetics, first published in
1955, gives a delightful description of Edward Dight, responsible for endowing the
Dight Clinic in Minneapolis, who lived in a house built in a tree and who failed to file
income tax returns. Reed also wrote a brief historical article on genetic counselling.
Reed’s book gives a vivid picture of the main areas covered in the early years of genetic
counselling, and it was Reed himself who first introduced the term. Many of the problems
are unchanged today and his examples of individual cases show that the fears and concerns
of families have altered little. In other respects, there have been profound changes in the
50 years since the book was written. Carrier detection was rarely possible and prenatal
diagnosis entirely non-existent, as was oral contraception, so the options open to patients
at risk were limited; either they took the risk or they did not. An even more important
change has been that of the general climate of opinion among the public and the medical
profession, in particular a greater openness in relation to family disorders.
Reed’s case histories illustrate the background of ignorance and prejudice with which
his patients had to cope, and it is no wonder that he found them grateful, even when he
could only give them pessimistic advice. He comes across as a caring and sensitive person,
upholding the concept of non-directiveness and turning his back completely on eugenics.
It is of interest that the most common cause of referral to the Dight Clinic was regard-
ing skin colour and whether a child for adoption would ‘pass for white’. Several other
problems among the 20 most common causes for referral listed by Reed are infrequently
encountered today, including eye colour, twinning and rhesus haemolytic disease.
 Genetic Counselling: an Introduction 5

The last of these provides a real example of advance in treatment and prevention; the
others reflect changes in social attitudes. Many others of Reed’s most common problems
remain equally important today, including mental handicap, schizophrenia, facial
clefting, neural tube defects and Huntington’s disease.
Most of the early genetic counselling clinics were run by non-medical scientists (like
Reed himself) or by those who were not experienced clinicians. With the growth in knowl-
edge of genetic disorders and the appearance of medical genetics as a distinct specialty
in the 1960s, genetic counselling progressively became medicalized, representing one of
the key components of clinical genetics. It was not, though, until later that the importance
of a firm psychological basis was recognized and became an essential part of genetic
counselling, the writings of Seymour Kessler making a particular contribution to this.
From around 1970, beginning in America, non-medical genetic counsellors with a
specific training in the field have become increasingly prominent, the graduate course
based at Sarah Lawrence College, New York, becoming the model for other centres in
America and Britain. As the demand for genetic counselling has grown, it has become
clear that not all consultations require the clinical expertise of the medical geneticist,
though careful coordination and mutual respect of the two groups are essential for an
optimal genetic counselling service.
At the time when I wrote the first edition of this book, 30 years ago, I had in mind the
general hospital clinician or family doctor as the main likely reader and the main provider
of genetic counselling, at least for relatively straightforward situations. It has been inter-
esting that only a few general clinicans have developed such a role; this is perhaps in part
because of lack of time, the most precious commodity for good genetic counselling. Also
it may reflect the fact that many clinicians wish to spend most of their time seeing and
managing sick patients, whereas much of genetic counselling involves the problems of
entirely healthy relatives. As genetics progressively spreads out in its applications beyond
specialist centres, there is a growing need for clinicians in different medical fields to
engage actively with the genetic counselling needs of those whom they see and also to
link more closely with their local medical genetics and genetic counselling centre.

CONSTRUCTING A FAMILY TREE

Collecting genetic information is the first and most important step in genetic counsel-
ling, and is best achieved by drawing up a family tree or pedigree. The use of clear and
consistent symbols allows genetic information to be set out much more clearly than
does a long list of relatives.
Drawing a satisfactory pedigree is not difficult, although it is remarkable how rarely
those clinicians without an interest in genetics will attempt the process. A clearly drawn
pedigree has a certain aesthetic appeal, but its chief value is to provide an unambiguous
and permanent record of the genetic information in a particular family. Although
computer programs exist, they are no substitute, in the author’s view, for a clearly drawn
pedigree constructed by hand at the time of the interview. A recent publication from the
UK Genetics Education Centre gives a clear and helpful guide to drawing a pedigree,
largely similar to the account given here.
6 Practical Genetic Counselling

Male, female (unaffected)

Sex unknown

Affected male and female

3 Three unaffected males

Examined personally
Deceased (and affected)

Individual without offspring

Consanguineous marriage

Offspring with parentage unacknowledged or different from expected

Abortion (spontaneous or induced)

Twins

Monozygotic twins

Heterozygote (autosomal recessive)

Heterozygote (X-linked)

Propositus

Figure 1.1 Symbols used in drawing a pedigree.

Figure 1.1 shows the main symbols used in constructing pedigrees. The symbols
shown for the sexes (䊐, 䊊) are preferred to the alternatives ( , ), which tend to be
confused at a distance. Heterozygous carriers can be denoted by half-shaded symbols or,
in the case of an X-linked disorder, by a central dot. Although the sign for an early
abortion (spontaneous or induced) can also be used for a stillbirth, it is preferable to
denote the sex of the latter with an appropriate symbol and indicate beneath the symbol
that it was a stillbirth. The previous use of a broken line for an offspring from outside
marriage is no longer appropriate. ‘Illegitimacy’ is no longer a meaningful concept in
most Western societies, but employing a broken line in a pedigree is still useful to repre-
sent the situation where parentage is unknown or unacknowledged.
The proband – also called the propositus (male) or proposita (female) – should be
clearly indicated with an arrow. The proband is the individual through whom the family
is ascertained. Large families will commonly have several probands. The proband is
generally an affected individual, but the person primarily seeking advice may well not
be affected. The term ‘consultand’ is conveniently used for this individual.
Multiple marriages and complex consanguinity can cause problems in constructing
a pedigree, and artistry will have to be sacrificed for accuracy in such cases. It is usually
 Genetic Counselling: an Introduction 7

Figure 1.2 Two examples of the ‘working pedigree’. These two pedigrees – one simple, the other
more extensive – show how family data can be easily and clearly recorded at the time of the interview.
A simple lined sheet is used; more detailed information on individuals can be recorded at the foot of
the pedigree or on the back. Identifying details have been deleted.

wise to start near the middle of the pedigree sheet and to leave more room than one
thinks will be needed, so that particularly prolific family branches do not become
crowded out. Figure 1.2 shows examples of the ‘working pedigree’, one simple and one
more complex.
The following practical points deserve emphasis.
• Enquire specifically about infant deaths, stillbirths and abortions. These may be
highly relevant, especially if structural abnormalities prove to have been present;
the fact that the information had not been volunteered may be significant. Thus
two children ‘lost at birth’ by the mother of a woman seen for counselling proved to
have both had spina bifida, a fact that considerably altered the risks.
8 Practical Genetic Counselling

• Consanguinity should be directly asked about and may be the clue that suggests
autosomal recessive inheritance (see Chapter 9). Equally, though, the background
level for consanguinity in the general population concerned must be taken into
account before attributing the problem to consanguinity.
• Mistaken or unacknowledged paternity must be borne in mind, especially in a
puzzling situation. A family doctor or nurse, particularly in a small community,
may well be able to clarify this possibility, but increasingly families are more open
about it, recognizing its importance in the context of genetic risk. Definitive tests of
paternity based on DNA (see Chapter 5) can help to resolve these problems more
easily, but DNA-based diagnostic tests may equally produce new difficulties by the
detection of unsuspected non-paternity.
• Always take at least basic details about both sides of the family, even in a
dominantly inherited disorder clearly originating from one side. Unexpected
findings may emerge. The family that insists that there is ‘nothing on our side’
should be regarded with suspicion until this is verified. Taking details about both
sides may also help to avoid feelings of guilt or blame resting exclusively on one
member of a couple, always an important factor, but particularly in some cultural
and social situations.
• Record dates of birth where possible rather than ages. Note the date when the
pedigree was drawn up.
• Record maiden names of women. This is especially significant for X-linked
disorders, where the surname of affected members is likely to change with each
generation.
• Note the addresses of key relevant members, though this is best done on a separate
sheet. This may prove invaluable in obtaining hospital records or in later contact
with relatives.
Most of the above points are obvious, yet it is surprising how often vital information is
not obtained unless a systematic approach is used.
In constructing a pedigree, it is not generally necessary to trace a person’s
ancestry back more than three or four generations; medical details often become
inaccurate at this early period. Sometimes, though, it may be important to link
kindreds or to establish a common ancestor, in which case genealogical records will
be useful. These are surprisingly abundant in many European countries, especially
Scandinavia. In the UK, a useful guide to the different sources has been produced
(see Bevan and Duncan, ‘Further reading’). Even in mobile populations such as in
America, the growth in interest in family history has considerably increased people’s
knowledge of their ancestors.

DIAGNOSTIC INFORMATION

It has already been emphasized that a clear diagnosis is the essential basis for accurate
genetic counselling. Unfortunately, this basis is all too often a shaky one, and one of the
principal tasks of anyone involved in genetic counselling is to ensure that it is made as