Chromosome Abnormalities and Genetic Counseling

649 Pages·2011·7.8 MB·English

by  R.J. McKinlay Gardner

chromosome abnormalities
and genetic counseling
OXFORD MONOGRAPHS ON MEDICAL GENETICS
General Editors:
judith g. hall peter s. harper louanne hudgkins evan eichler charles j. epstein†* arno g. motulsky
Former Editors:
charles scriver martin bobrow j.a. fraser roberts c.o. carter h an brenner
1. R.B. McConnell: Th e genetics of gastrointestinal disorders
2. A.C. Kopéc: Th e distribution of the blood groups in the United Kingdom
3. E. Slater and V.A. Cowie: Th e genetics of mental disorders
4. C.O. Carter and T.J. Fairbank: the genetics of locomotor disorders
5. A.E. Mourant, A.C. Kopéc, and K. Domaniewska-Sobezak: Th e distribution of the human blood groups and other polymorphisms
6. A.E. Mourant, A.C. Kopéc, and K. Domaniewska-Sobezak: Blood groups and diseases
7. A.G. Steinbert and C.E. Cook: Th e distribution of the human immunoglobulin allotypes
8. D. Tills, A.C. Kopéc, and R.E. Tills Th e distribution of the human blood groups and other polymorphisms: Supplement I
9. D.Z. Loesch: Quantitative dermatoglyphics: classifi cation, genetics, and pathology
10. D.J. Bond and A.C. Chandley: Aneuploidy
11. P.F. Benson and A.H. Fensom: Genetic biochemical disorders
12. G.R. Sutherland and F. Hecht: Fragile sites on human chromosomes
13. M. d’A Crawfurd: Th e genetics of renal tract disorders
14. C.R. Scriver and B. Child: Garrod’s inborn factors in disease
18. M. Baraitser: Th e genetics of neurological disorders
19. R.J. Gorlin, M.M. Cohen, Jr. and L.S. Levin: Syndromes of the head and neck, third edition
21. D. Warburton, J. Byrne, and N. Canki: Chromosome anomalies and prenatal development: an atlas
2 2. J.J. Nora, K. Berg, and A.H. Nora: Cardiovascular disease: genetics, epidemiology, and prevention
24. A.E.H. Emery: Duchenne muscular dystrophy, second edition
25. E.G.D. Tuddenham and D.N. Cooper: Th e molecular genetics of haemostasis and its inherited disorders
26. A. Boué: Foetal medicine
27. R.E. Stevenson, J.G. Hall, and R.M. Goodman: Human malformations
28. R.J. Gorlin, H.V. Toriello, and M.M. Cohen, Jr.: Hereditary hearing loss and its syndromes
29. R.J. M. Gardner and G. R. Sutherland: Chromosomes abnormalities and genetic counseling, second edition
30. A.S. Teebi and T.I. Farag: Genetic disorders among Arab populations
31. M.M. Cohen, Jr.: Th e child with multiple birth defects
32. W.W. Weber: Pharmacogenetics
33. V.P. Sybert: Genetic skin disorders
34. M. Baraitser: Genetics of neurological disorders, third edition
35. H. Ostrer: Non-Mendelian genetics in humans
36. E. Traboulsi: Genetic factors in human disease
37. G.L. Semenza: Transcription factors and human disease
38. L. Pinsky, R.P. Erickson, and R.N. Schimke: Genetic disorders of human sexual development
39. R.E. Stevenson, C.E. Schwartz, and R. J. Schroer: X-linked mental retardation
40. M.J. Khoury, W. Burke, and E. & Th omson: Genetics and public health in the 21st century
41. J. Weil: Psychosocial genetic counseling
42. R.J. Gorlin, M.M. Cohen, Jr., and R.C.M. Hennekam: Syndromes of the head and neck, fourth edition
43. M.M. Cohen, Jr., G. Neri, and R. Weksberg: Overgrowth syndromes
44. R.A. King, J.I. Rott er, and A.G. Motulsky: & e genetic basis of common diseases, second edition
45. G.P. Bates, P.S. Harper, and L. Jones: Huntington’s disease, third edition
46. R.J.M. Gardner and G.R. Sutherland: Chromosome abnormalities and genetic counseling, third edition
47. I.J. Holt: Genetics of mitochondrial disease
48. F. Flinter, E. Maher, and A. Saggar-Malik: & e genetics of renal disease
49. C.J. Epstein, R.P. Erickson, and A. Wynshaw-Boris: Inborn errors of development: the molecular basis of clinical disorders of morphogenesis
50. H.V. Toriello, W. Reardon, and R.J. Gorlin: Hereditary hearing loss and its syndromes, second edition
51. P. S. Harper: Landmarks in medical genetics
52. R.E. Stevenson and J.G. Hall: Human malformations and related anomalies, second edition
53. D. Kumar and S.D. Weatherall: Genomics and clinical medicine
54. C.J. Epstein, R.P. Erickson, and A. Wynshaw-Boris: Inborn errors of development: the molecular basis of clinical disorders of morphogenesis,
second edition
55. W. Weber: Pharmacogenetics, second edition
56. P.L. Beales, I.S. Farooqi, and S. O’Rahilly: Th e genetics of obesity syndromes
57. P.S. Harper: A short history of medical genetics
58. R.C.M. Hennekam, I.D. Krantz, and J.E. Allanson: Gorlin’s syndromes of the head and neck, fi ft h edition
59. D. Kumar and P. Elliot: Principles and practices of cardiovascular genetics
60. V.P. Sybert: Genetic skin disorders, second edition
61. R.J.M. Gardner, G.R. Sutherland, and L.G. Shaff er: Chromosome Abnormalities and Genetic Counseling, fourth edition
† Deceased
oxford monographs on medical genetics no. 61
chromosome
abnormalities and
genetic counseling
FOURTH EDITION
R. J. McKinlay GARDNER
ADJUNCT PROFESSOR
UNIVERSITY OF OTAGO, DUNEDIN, NEW ZEALAND
AND NORTHERN REGIONAL GENETIC SERVICES
AUCKLAND, NEW ZEALAND
(LATELY OF GENETIC HEALTH SERVICES VICTORIA
MELBOURNE, AUSTRALIA)
Grant R. SUTHERLAND
EMERITUS GENETICIST
WOMEN’S AND CHILDREN’S HOSPITAL , AND AFFILIATE PROFESSOR
UNIVERSITY OF ADELAIDE, ADELAIDE, AUSTRALIA
Lisa G. SHAFFER
SIGNATURE GENOMIC LABORATORIES
SPOKANE, WASHINGTON, UNITED STATES OF AMERICA
1
1

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____________________________________________________________________________________
Library of Congress Cataloging-in-Publication Data
Gardner, R. J. M.
Chromosome abnormalities and genetic counseling / R.J. McKinlay Gardner, Grant R. Sutherland, Lisa G. Shaff er. — 4th ed.
p. ; cm. — (Oxford monographs on medical genetics ; no. 61)
Includes bibliographical references and index.
ISBN 978-0-19-537533-6
1. Genetic counseling. 2. Human chromosome abnormalities—Patients—Counseling of. I. Sutherland, Grant R.
II. Shaff er, Lisa G. III. Title. IV. Series: Oxford monographs on medical genetics ; no. 61.
[DNLM: 1. Chromosome Aberrations. 2. Genetic Counseling. QS 677]
RB155.7.G37 2011
616’.042—dc22 2011005028
____________________________________________________________________________________
9 8 7 6 5 4 3 2 1
Printed in USA
on acid-free paper
Th is book is dedicated to Jocelyn, Geoff rey, and Craig, their parents, and all other
families who seek our “chromosomal advice.”
Jocelyn and Geoff rey (with lamb) have a partial trisomy for chromosome 4 long arm, and
Craig, the youngest, had a 46,XY result on amniocentesis. Th eir father is a translocation
carrier (see Fig. 5–1, lower).
Heredity Where is the wisdom we have lost in knowledge?
Inescapably, this is me—the diagnosis Where is the knowledge we have lost in information?
is cause for anger at those
— T. S. Eliot
who brightly say we choose our destinies.
Th ere is no store
Curiosity is a virtue, perhaps an unsung and underval-
of courage, wit or will
ued virtue, which should be the energizing fuel to the
can save me fr om myself and I must face
thinking geneticist.
my children, feeling like
that wicked fairy, uninvited — Willie Reardon
at the christening, bestowing on my own,
amidst murmurs of apprehension, a most
unwanted gift —that
of a blighted mind. No one
could tell me of this curse when I
was young and dreamt of children
and the graces they would bear. Later,
it seemed that a chill morning
revealed deeper layers
of truth. For my romancing
there is a price to pay—
perhaps my children’s children
will pass this tollgate aft er me.
My grandmothers gaze down fr om their fr ames
on my wall, sadly wondering.
— Meg Campbell
preface to fourth edition
Plus ça change, plus c’est la même chose . Classicists see continue to be born, with an incorrect chromosomal
the chromosome as a vertical structure; to the complement. And people still want to know why,
molecular scientist, DNA may lie horizontally: but and what they can do about it.
they are looking at the same thing. Th e move away Th e distinction between chromosome abnor-
from classical microscopy into molecular method- malities and mutations in single gene diseases has
ologies, predicted for some time, is now actually become somewhat blurred. Some single gene muta-
happening. Smaller and subtler abnormalities can tions can be due to relatively large deletions, and
be detected. We know a lot more (but much some “cytogenetically” detected abnormalities can
yet to know) about normal genomic variation. be deletions and duplications of smaller size. We
Chromosomal testing of embryos before implanta- deal primarily with those conditions that are
tion, while not commonplace, is no longer regarded detected in the expanded molecular cytogenetics
as extraordinary. Much progress is being made in laboratory, being aware that, for some of these, the
enabling screening in pregnancy to be done earlier, risk assessments will follow those of dominant dis-
and with greater precision. orders. We have retained the fragile X syndromes,
Be all this as it may, human biology remains since these originated as chromosome disorders; in
human biology. Meiosis is as vulnerable as it always some respects, the molecular approach has simplifi ed
has been. Chromosomes continue to undergo rear- counselling, but in other ways, it has become more
rangement. Conceptions still happen, and children complicated. A twenty-fi rst-century chromosome
• vii
report is a sophisticated document, and it behoves but mostly, these are questions we’ve heard many
the counselor to read it with an informed mind. We times before.
have therefore added a chapter devoted to the new
technologies.
So this book is changing, but it is also the same Dunedin and Auckland R.J.M.G.
thing. We can answer some questions more accu- Adelaide G.R.S.
rately, indeed a lot more accurately, than hitherto; Spokane L.G.S.
viii • PREFACE TO FOURTH EDITION
preface to the first edition
We have writt en this book with two particular cate- again? Most chapters follow the general format of a
gories of reader in mind. Th e fi rst, and chief, audi- Biology section, which discusses the fi rst question,
ence is the genetic counselor, the person whose role and a Genetic Counseling section, which deals with
it is to explain and interpret a chromosomal prob- the latt er two. (Th e division is not always clear-cut,
lem to the individual or family in whom it has been and recognizing that readers may at times wish to
identifi ed. Second, we have considered the needs of refer just to the Genetic Counseling section, there is
cytogenetic laboratory workers, who in addition to some duplication.) We do not claim, in using the
possessing the technical skills for chromosomal expression “genetic counseling,” to encompass all
analysis, should understand the theoretical basis of that is involved in this multifaceted process. Rather,
clinical cytogenetics and be aware of the practical we seek to provide information and fi gures that will
implications of their work. assist the client to decide what, for them, would be
A pithy defi nition of counseling is assisting an appropriate course of action and to provide
clients to recognize the nature of their problems and pointers to assist the counselor in communicating
to fi nd their own solutions to them. Th e description that information.
applies aptly to the specifi c case of genetic counsel- Chromosomes are not a theoretical concept;
ing. One tool the counselor needs to do the job well they are real things. (In this spirit, it is helpful in
is accurate information about the nature of the prob- counseling sessions to have on hand a real karyo-
lem. Th e aim of this book is to provide in convenient type, preferably from the counselee’s own family,
form accurate information concerning chromo- for use as a teaching aid.) To be able to give to the
somal conditions. We address these major questions concept of chromosomes being passed down from
clients have: How and why did it happen? Could it parent to child a sense of reality, the counselor
happen again? If so, how likely would it be to happen should have a broad and comfortable understanding
• ix