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 GARDNER AND SUTHERLAND’S
CHROMOSOME ABNORMALITIES
AND GENETIC COUNSELING

2
OXFORD MONOGRAPHS ON MEDICAL GENETICS
General Editors:
JUDITH G. HALL PETER S. HARPER LOUANNE HUDGKINS EVAN EICHLER CHARLES J.
EPSTEIN (DECEASED 2011) ARNO G. MOTULSKY (RESIGNED 2011)

1. R. B. McConnell: The genetics of gastrointestinal disorders

2. A. C. Kopéc: The distribution of the blood groups in the United Kingdom
3. E. Slater and V. A. Cowie: The 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: The 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: The distribution of the human immunoglobulin
allotypes
8. D. Tills, A. C. Kopéc, and R. E. Tills: The distribution of the human blood
groups and other polymorphisms: Supplement I
10. D. Z. Loesch: Quantitative dermatoglyphics: Classification, genetics, and
pathology
11. D. J. Bond and A. C. Chandley: Aneuploidy
12. P. F. Benson and A. H. Fensom: Genetic biochemical disorders
13. G. R. Sutherland and F. Hecht: Fragile sites on human chromosomes
14. M. d’A Crawfurd: The genetics of renal tract disorders
16. C. R. Scriver and B. Child: Garrod’s inborn factors in disease
18. M. Baraitser: The 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
22. 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: The 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.: The child with multiple birth defects
32. W. W. Weber: Pharmacogenetics

3
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. Thomson: 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. Rotter, and A. G. Motulsky: 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: 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: The 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, fifth 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. C. Shaffer: Chromosome
abnormalities and genetic counseling, fourth edition
62. D. Kumar: Genomics and health in the developing world
63. G. Bates, S. Tabrizi, and L. Jones: Huntington’s disease, fourth edition

4
64. B. Lee and F. Scaglia: Inborn errors of metabolism: From neonatal screening
to metabolic pathways
65. D. Kumar and C. Eng: Genomic medicine, second edition
66. R. Stevenson, J. Hall, D. Everman, and B. Solomon: Human malformations
and related anomalies, third edition
67. R. Erickson and A. Wynshaw-Boris: Epstein’s inborn errors of development:
The molecular basis of clinical disorders of morphogenesis, third edition
68. C. Hollak and R. Lachmann: Inherited metabolic disease in adults: A clinical
guide
69. V. P. Sybert: Genetic skin disorders, third edition
70. R. J. M. Gardner and D. J. Amor: Gardner and Sutherland’s chromosome
abnormalities and genetic counseling, fifth edition

5
 GARDNER AND SUTHERLAND’S

Chromosome Abnormalities and

Genetic Counseling
FIFTH EDITION

R. J. McKinlay GARDNER
ADJUNCT PROFESSOR
CLINICAL GENETICS GROUP
UNIVERSITY OF OTAGO, DUNEDIN, NEW ZEALAND

David J. AMOR
LORENZO AND PAMELA GALLI CHAIR
UNIVERSITY OF MELBOURNE
VICTORIAN CLINICAL GENETICS SERVICES
MURDOCH CHILDREN’S RESEARCH INSTITUTE
ROYAL CHILDREN’S HOSPITAL, MELBOURNE, AUSTRALIA

6
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Library of Congress Cataloging-in-Publication Data

Names: Gardner, R. J. M., author. | Amor, David J., author.
Title: Gardner and Sutherland’s chromosome abnormalities and genetic counseling / R. J. McKinlay
Gardner, David J. Amor.
Other titles: Chromosome abnormalities and genetic counseling | Oxford monographs on medical
genetics ; no. 70.
Description: Fifth edition. | Oxford ; New York : Oxford University Press, [2018] |
Series: Oxford monographs on medical genetics ; no. 70 | Preceded by Chromosome abnormalities
and genetic counseling / R.J. McKinlay Gardner, Grant R. Sutherland, Lisa G. Shaffer. c2012. |
Includes bibliographical references and index.
Identifiers: LCCN 2017034126 | ISBN 9780199329007 (hardcover : alk. paper) | ISBN
9780199329021 (epub)
Subjects: | MESH: Chromosome Aberrations | Genetic Counseling
Classification: LCC RB155.7 | NLM QS 677 | DDC 616/.042—dc23 LC record available at
https://lccn.loc.gov/2017034126

This material is not intended to be, and should not be considered, a substitute for medical or other
professional advice. Treatment for the conditions described in this material is highly dependent on
the individual circumstances. And, while this material is designed to offer accurate information with
respect to the subject matter covered and to be current as of the time it was written, research and
knowledge about medical and health issues is constantly evolving and dose schedules for
medications are being revised continually, with new side effects recognized and accounted for
regularly. Readers must therefore always check the product information and clinical procedures
with the most up-to-date published product information and data sheets provided by the
manufacturers and the most recent codes of conduct and safety regulation. The publisher and the
authors make no representations or warranties to readers, express or implied, as to the accuracy or
completeness of this material. Without limiting the foregoing, the publisher and the authors make
no representations or warranties as to the accuracy or efficacy of the drug dosages mentioned in the
material. The authors and the publisher do not accept, and expressly disclaim, any responsibility for
any liability, loss or risk that may be claimed or incurred as a consequence of the use and/or
application of any of the contents of this material.

7
 This book is dedicated to Jocelyn, Geoffrey, and Craig, their
parents, and all other families who seek our “chromosomal
advice.”

Jocelyn and Geoffrey (with lamb) have a partial trisomy for

chromosome 4 long arm, and Craig, the youngest, had a 46,XY
result on amniocentesis. Their father is a translocation carrier (see
Fig. 5–1, lower). Craig, since married, came to the genetic clinic

8
for confirmatory advice about his low genetic risk.

9
Heredity
Inescapably, this is me—the diagnosis
is cause for anger at those
who brightly say we choose our destinies.
There is no store
of courage, wit or will
can save me from myself and I must face
my children, feeling like
that wicked fairy, uninvited
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 after me.
My grandmothers gaze down from their frames
on my wall, sadly wondering.
—Meg Campbell

Dear DNA
In real life you’re just
a tangle of white filaments
captured in a test-tube,
and your first photo is not flattering:
grey smudges like tractor tracks,
or a rusty screw. Yet
many say you are beautiful.
Online for a night
with a hundred fantastic portraits

10
and I’m head over heels
In love with you, DNA,
bewitched by your billions
coiled in my cells, transcribing,
replicating, mutating.
I see your never-ending dance.
A length of twisted ladder
briefly unwinds,
both strands duplicate,
each copy drifts away
on its secret mission
to make a thought, feel sunshine,
or digest this morning’s porridge.
Two winding parallel threads,
a tiny tangle of gossamer
designing my life.
DNA, you are astonishing
and I am yours truly.
—Winifred Kavalieris

Genes pass on our kind

But our selves are transmitted
In words left behind.
—J. Patrick Gookin

Curiosity is a virtue, perhaps an unsung and undervalued virtue, which

should be the energizing fuel to the thinking geneticist.
—Willie Reardon

Where is the wisdom we have lost in knowledge?

Where is the knowledge we have lost in information?
—T. S. Eliot

11
 PREFACE TO THE FIFTH EDITION

Chromosomal disorders have been, and will always be, with us; that is a
given. What is changing is our ability to recognize and detect them:
detection both in terms of the subtlety of abnormalities and of the means
we can use to find them. Classical cytogenetics has now well and truly
given way to “molecular karyotyping,” and this has been the extraordinary
development of the early twenty-first century. Readers will now be as
accustomed to molecular nomenclature in defining a segment, such as
chr5:1-18,500,000, as they had been to the classical description,
5p14.1→pter.
The very small deletions and duplications which molecular karyotyping
can now reveal have become familiar to the clinicians and counselors who
see patients and families in the clinic. A large number of these are now on
record, many attracting the nomenclature “copy number variant”: Some
are very well understood, others becoming so, and yet quite a few—
variants of uncertain significance, the acronym “VOUS” in daily parlance
—whose roles in human pathology are imperfectly appreciated. Many are
not in the same mold as the deletions and duplications of classical
cytogenetics, in which the single defect sufficed to cause a particular
phenotype, and always did so: We now need to take account of the concept
of incomplete penetrance, with some microdeletions or duplications not, of
themselves, always leading to an abnormal phenotype. Apparently
clinically normal parents may carry the same alteration as their child with
an abnormal phenotype. Digenic, or “two-hit,” mechanisms may now
require consideration. These were not formerly notions much entering into
the assessment of chromosomal disorders; discussion apropos in the clinic
presents a new challenge.
The number of “new” del/dup syndromes increases almost with each
issue of the clinical genetic journals. We include a mention of a
considerable number of these here (Chapter 14), not intending to create an
encyclopedic resource per se but believing that such a record may provide
a useful first point of contact when these cases are encountered in the
clinic. Copy number variants of uncertain significance, on the other hand,
we mostly take only a broad rather than a detailed view (Chapter 17); the

12
reader will need to consult other repositories for fuller information, as their
interpretations evolve.
The new (or now, established) laboratory methodologies blur the
boundaries between what might have been regarded as the classic
chromosomal abnormalities and Mendelian conditions. Some disorders
recorded as being due not only to segmental deletion/duplication affecting
a single locus but also to point mutation at that locus we continue to treat
as “chromosomal”; and for most, their place in this book is secure. But one
major category, the fragile X syndromes, are now seen as essentially
Mendelian disorders, their historic cytogenetic-based nomenclature
notwithstanding, and they no longer claim their chapter.
Peripheral blood and skin have been the tissues in common usage for
chromosome analysis, with an increasing role for cells got from the
convenient and painless “spit sample.” Prenatal diagnosis has been based
on amniocentesis and chorionic villus sampling, but latterly blastomeres
from early embryos, and fetal DNA in the maternal circulation, have
become targets for testing. Now we can anticipate the potential for whole
genome analysis to be applied to the prenatal diagnosis of the classic
aneuploidies, from a simple maternal blood sample, and this would widen
such testing very considerably. Questions such as these raise ethical issues,
and a literature on “chromosomal ethics” is accumulating.
As we have previously written, however marvelous may be these new
ways to test for chromosomes, the concerns of families remain essentially
the same. We may reproduce here the final paragraph of the Preface of the
first edition of this book, from 1989, as valid now as then:
Families pursue genetic counseling in an effort to demystify the mysterious.
If they did not want to “hear it all,” they would not bother with genetic
counseling. Families want an honest evaluation of what is known and what is
unknown, a clear explanation of all possibilities, both good and bad, and a
sensitive exploration of all available information with which they can make
knowledgeable decisions about future family planning. Thus, Bloch et al.
(1979) succinctly convey the essence of why people go to the genetic
counselor. We hope this book will assist counselors in their task.

Dunedin R.J.M.G.
Melbourne D.J.A.
February 2018

13
 ACKNOWLEDGMENTS

We thank John Barber, Rachel Beddow, Amber Boys, Cyril Chapman,

Jane Halliday, Jan Hodgson, Caroline Lintott, Nicole Martin, Belinda
McLaren, Fiona Norris, Mamoru Ozaki, Mark Pertile, Jenny Rhodes,
Sharyn Stock-Myer, and Jane Watt for their critical advice. We
acknowledge Lisa Shaffer, who was a co-author of the previous edition,
and much of whose work has flowed over into this edition. We have made
much use of the ideograms created by Nicole Chia. The length of the
Reference list, and the frequency with which we acknowledge, in legends
to figures, the courtesy of colleagues whose work we use, speaks for the
debt we owe to our colleagues in clinical cytogenetics worldwide.
Belatedly, R.J.M.G. thanks Ngaire Adams and Dianne Grimaldi, whose
need for chromosomal teaching at Dunedin Hospital in the 1980s provided
the germination for writing this book. We have appreciated the wise
guidance, and the patience and forbearance of Oxford University Press,
from Jeff House when this book made its first appearance, through to Chad
Zimmerman and Chloe Layman in this fifth edition. R.J.M.G. thanks his
wife Kelley for her patient help, once again, in document management;
and the front cover art, and most of the new illustrations in this edition,
have been drawn, or redrawn, by her.

14
 CONTENTS

PART ONE: BASIC CONCEPTS

1. Elements of Medical Cytogenetics
2. Chromosome Analysis
3. The Origins and Consequences of Chromosome Pathology
4. Deriving and Using a Risk Figure

PART TWO: PARENT OR CHILD WITH A CHROMOSOMAL

ABNORMALITY
5. Autosomal Reciprocal Translocations
6. Sex Chromosome Translocations
7. Robertsonian Translocations
8. Insertions
9. Inversions
10. Complex Chromosomal Rearrangements
11. Autosomal Ring Chromosomes
12. Centromere Fissions, Complementary Isochromosomes,
Telomeric Fusions, Balancing Supernumerary Chromosomes,
Neocentromeres, Jumping Translocations, and Chromothripsis
13. Down Syndrome, Other Full Aneuploidies, Polyploidy, and the
Influence of Parental Age
14. Autosomal Structural Rearrangements: Deletions and
Duplications
15. Sex Chromosome Aneuploidy and Structural Rearrangement
16. Chromosome Instability Syndromes

PART THREE: CHROMOSOME VARIANTS

15
17. Normal Chromosomal Variation

PART FOUR: DISORDERS ASSOCIATED WITH ABERRANT

GENOMIC IMPRINTING
18. Uniparental Disomy and Disorders of Imprinting

PART FIVE: REPRODUCTIVE CYTOGENETICS

19. Reproductive Failure
20. Prenatal Testing Procedures
21. Chromosome Abnormalities Detected at Prenatal Diagnosis
22. Preimplantation Genetic Diagnosis

PART SIX: DISORDERS OF SEX DEVELOPMENT

23. Chromosomal Disorders of Sex Development

PART SEVEN: NOXIOUS AGENTS

24. Gonadal Cytogenetic Damage from Exposure to Extrinsic Agents

APPENDICES
A. Ideograms of Human Chromosomes, and Haploid Autosomal
Lengths
B. Cytogenetic Abbreviations and Nomenclature
C. Determining 95 Percent Confidence Limits, and the Standard
Error

References
Index

16
 PART ONE
BASIC CONCEPTS

17
 1
ELEMENTS OF MEDICAL
CYTOGENETICS

CHROMOSOMES WERE first seen and named in the late nineteenth

century. Chromosome is a combination of Greek words meaning colored
(chrom) body (soma); the word was coined by the illustrious German
anatomist Heinrich Wilhelm Gottfried von Waldeyer-Hartz. It was early
appreciated that these brightly staining objects appearing in the cell
nucleus must be the “stuff of heredity,” the very vessels of our genetic
inheritance. Most observers had concluded, in the earlier part of the
twentieth century, that the human chromosome count was 48. It was not
until the 1950s, due to technical advances, and in particular the use of a
hypotonic solution to swell the cells, giving an uncluttered view of the
chromosomes, that Joe Hin Tjio and Albert Levan could recognize that 46
was the correct number. This discovery spurred research into conditions in
which a chromosomal cause had hitherto been suspected, and in 1959 (“the
wonderful year of human cytogenetics”) came the first demonstrations of a
medical application of the new knowledge, with practically simultaneous
discoveries of the chromosomal basis of Down syndrome, Klinefelter
syndrome, and Turner syndrome (Lejeune et al.1 1959; Jacobs and Strong
1959; Ford et al. 1959); these were followed soon thereafter by the
recognition of the other major aneuploidy syndromes. Harper (2006)
records the history, and the personalities behind the history, in his book
First Years of Human Chromosomes—a book that should be read by every
student of medical cytogenetics with an interest in how their discipline
came to be. Harper points out that the practice of genetic counseling came
into its own essentially upon the basis of these chromosomal discoveries:
So to speak, geneticists now had “their organ.”
“Colored bodies” became an especially apt derivation with the
development of various different staining techniques in the 1980s and
1990s, showing different parts of chromosomes in many different colors,

18
whether true or computer-generated false colors. The images produced by
this kaleidoscopic karyotyping could be rather beautiful. Black-and-white
photographs were less splendid but often sufficed (Figure 1–1). Albeit that
molecular methodologies have substantially taken over from classical
cytogenetics, and providing a different view of the genetic material, the
word chromosome will surely last forever.

FIGURE 1–1 The appearance of banded chromosomes, from a classical

cytogenetic study.

Chromosomal Morphology
Chromosomes have a linear appearance: two arms that are continuous at
the centromere. Reflecting the French influence in the establishment of the
cytogenetic nomenclature, the shorter arm is designated p (for petit), and
the longer is q (variously explained as being the next letter in the alphabet,
a mistyping of g (for grand), for queue, or as the other letter in the formula

19
p + q = 1). In the early part of the cell cycle, each chromosome is present
as a single structure, a chromatid, a single DNA molecule. During the cell
cycle, the chromosomes replicate, and two sister chromatids form. Now
the chromosome exists as a double-chromatid entity. Each chromatid
contains exactly the same genetic material. This replication is in
preparation for cell division so that, after the chromosome has separated
into its two component chromatids, each daughter cell receives the full
amount of genetic material. It is during mitosis that the chromosomes
contract and become readily distinguishable on light microscopy.
Blood and buccal mucosal cells are the tissues from which DNA is
extracted in routine chromosome analysis. From blood, the nucleated
white cell is the tested component for microarray analysis, and in classical
cytogenetic analysis, it is the lymphocyte. Buccal mucosal cells and white
blood cells2 are obtained from a saliva sample. The chromosomal status of
each small sample is taken as representative of the constitution of
(essentially) every other cell of the body. In the case of invasive prenatal
diagnosis, the cells from amniotic fluid or chorionic villi are the source
material; these tissues are assumed (with certain caveats) to represent the
fetal chromosomal constitution. Noninvasive prenatal diagnosis exploits
the presence of fetal blood cells and DNA in the maternal circulation.
The 46 chromosomes come in 23 matching pairs and constitute the
genome. One of each pair came from the mother, and one from the father.
For 22 of the chromosome pairs, each member (each homolog) has the
same morphology in each sex: These are the autosomes. The sex
chromosome (or gonosome) constitution differs: The female has a pair of
X chromosomes, and the male has an X and a Y chromosome. The single
set of homologs—one of each autosome plus one sex chromosome—is the
haploid set. The haploid number (n) is 23. The haploid complement exists,
as such, only in the gametocytes (ovum and sperm). All other cells in the
body—the soma—have a double set: the diploid complement (2n) of 46. If
there is a difference between a pair of homologs, in the sense of one being
structurally rearranged, the person is described as a heterozygote.
The chromosomes are classically distinguishable on the basis of their
size, centromere position, and banding pattern. The centromere may be in
the middle, off-center, or close to one end—metacentric, submetacentric,
and acrocentric, respectively. The chromosomes are numbered 1 through
22, and X and Y, and are also assigned to groups A through G, according
to their general size and the position of the centromere. The diagrammatic
representation of the banding pattern is the ideogram (Appendix A). The
numbering is based on size, largest to smallest (to split hairs, this order is

20
not exact; for example, chromosomes 10 and 11 are shorter than
chromosome 12, and chromosome 21 is smaller than 22).
The classical format of a chromosome display, the “karyotype,” has the
chromosomes lined up with p arms upward, in their matching pairs (Figure
1–2). Those coming from a DNA-based view may see the chromosome
lying on its side, and microarray reports usually show a horizontal
depiction of the chromosome arms, with the graph indicating duplications
and deletions by a rise or a fall compared to baseline, respectively
(although no one is proposing that short and long arms be renamed as left
and right!). Karyotypes are described according to a shorthand notation,
the International System of Human Cytogenetic Nomenclature (ISCN
2016); an outline is given in Appendix B.

FIGURE 1–2 Chromosomes arranged as a formal karyotype, from a classical

cytogenetic study.

Chromosomal Structure
Chromatin exists in differently condensed forms: the less condensed

21
euchromatin and the more condensed heterochromatin. Euchromatin
contains the coding DNA—the genes—while heterochromatin comprises
noncoding DNA. Chromosomes are capped at the terminal extremities of
their long and short arms by telomeres, specialized DNA sequences
comprising many repeats of the sequence TTAGGG, that can be thought of
as sealing the chromatin and preventing its fusion with the chromatin of
other chromosomes. The centromere 3 is a specialized region of DNA that,
at mitosis, provides the site at which the spindle apparatus can be anchored
and draw each separated chromatid to opposite poles of the dividing cell.
Centromeric heterochromatin contains “satellite DNA,” so-called because
these DNA species have different buoyant densities and produce distinct
humps on a density gradient distribution. (These are not to be confused
with the satellites on acrocentric chromosomes.) A separate issue, of
considerable academic interest (but which we shall take no further here), is
the “packaging question”: how the centimeters of DNA are compacted into
micron-length chromosomes, and which parts of the nucleus each
chromosome occupies (Annunziato 2008; Lieberman-Aiden et al. 2009).

CHROMOSOME ABNORMALITY
Chromosomes are distributed to each daughter cell during cell division in a
very precise process—precise, but prone to error. From our perspective,
the two cell divisions of meiosis, during which the gametes are formed, are
of central importance. Most of the discipline of medical cytogenetics
focuses on the consequences of disordered meiosis having produced a
chromosomally abnormal gamete, causing a chromosomal abnormality in
the conceptus. A chromosome abnormality that is present from conception
and involves the entire body is a constitutional abnormality. If an
additional cell line with a different chromosomal complement arises before
the basis of the body structure is formed (that is, in embryonic or pre-
embryonic life) and becomes an integral part of the organism,
constitutional mosaicism results. In this book, we concern ourselves
practically solely with constitutional abnormalities. Acquired
chromosomal abnormality of course exists, and indeed it is a major
initiating and sustaining cause in most cancers, a fact first proposed by
Boveri in 1914 and voluminously attested in the work of Mitelman et al.
(2016); but this is more the field of study of the molecular pathologist than
the genetic counselor.
An incorrect amount of genetic material carried by the conceptus
disturbs and distorts its normal growth pattern (from zygote → blastocyst

22
→ embryo → fetus). In trisomy, there is three of a particular chromosome,
instead of the normal two. In monosomy, only one member of the pair is
present. Two of each is the only combination that works properly! It is
scarcely surprising that a process as exquisitely complex as the
development of the human form should be vulnerable to a confused
outflow of genetic instruction from a nucleus with a redundant or
incomplete database.
Trisomy and monosomy for a whole chromosome were the first
cytogenetic mechanisms leading to an abnormal phenotype to be
identified. More fully, we can list the following pathogenetic mechanisms
that arise from chromosomal abnormalities:

1. A dosage effect, with a lack (deletion) or excess (duplication) of

chromosomal material, whether for a whole chromosome or a part of a
chromosome. This is by far the predominant category.
2. A direct damaging effect, with disruption of a gene at the breakpoint
of a rearrangement
3. An effect due to the incongruent parental origin of a chromosome or
chromosomal segment (genomic imprinting)
4. A position effect, whereby a gene in a new chromosomal
environment functions inappropriately
5. Combinations of the above

We discuss these mechanisms in more detail in following chapters.

Autosomal Imbalance
STRUCTURAL IMBALANCE
As noted earlier, imbalance may involve the gain or loss of a whole
chromosome—full aneuploidy—or of part of a chromosome—partial
aneuploidy. The abnormality may occur in the nonmosaic or mosaic state.
Loss (that is, monosomy) of chromosomal material generally has a more
devastating effect on growth of the conceptus than does an excess of
material (that is, trisomy). Certain imbalances lead to certain abnormal
phenotypes. The spectrum is listed in outline in Box 1–1. Most full
autosomal trisomies and virtually all full autosomal monosomies set
development of the conceptus so awry that, sooner or later, abortion occurs
—the embryo “self-destructs” and is expelled from the uterus. This issue is
further explored in Chapter 19. A few full trisomies are not necessarily

23
lethal in utero, and many partial chromosomal aneuploidies are associated
with survival through to the birth of an infant.

Box 1–1 The Spectrum of Effects, in Broad Outline, Resulting from

Constitutional Chromosomal Abnormality

1. Devastation of blastogenesis, with transient implantation or

nonimplantation of the conceptus
2. Devastation of embryogenesis, with spontaneous abortion, usually in
the first trimester
3. Major disruption of normal intrauterine morphogenesis, with
stillbirth or early neonatal death
4. Major disruption of normal intrauterine morphogenesis, but with
some extrauterine survival
5. Moderate distortion of normal intrauterine development, with
substantial extrauterine survival and severe mental retardation
6. Mild distortion of normal intrauterine development, with substantial
extrauterine survival, and considerable intellectual compromise
7. Minimal physical phenotypic effect, varying degrees of intellectual
compromise; possible compromise of fertility
8. No discernible physical phenotypic effect; cognitive function within
the normal range, but less than expected from the family background

Characteristically, “survivable imbalances” produce a phenotype of

widespread dysmorphogenesis, and there may be malformation of internal
organs and limbs. It is often in the facial appearance (facies) that the most
recognizable physical abnormality is seen, with Down syndrome the
classic example, although the physical phenotype in some cases of subtler
deletion or duplication may be rather “bland.” The most complex organ of
all, the brain, is the most vulnerable to a less than optimal genetic
constitution, and some compromise of mental and intellectual functioning,
usually to the extent of an obvious deficit, is nearly invariable, at least in
imbalances of classical size. With several of the (much smaller)
imbalances due to copy number variants, developmental delay or mental
retardation4 with an outwardly normal physical phenotype is well
recognized as a chromosomal presentation. Thus, the central concern of
most people seeking genetic counseling for a chromosomal condition is
that of having a child who might have a physical, intellectual, or severe

24
social handicap.
Historically, the chromosomal basis of many syndromes was identified
following analysis of groups of patients with similar phenotypes. This
“phenotype-first” approach led to the identification of many of the well-
known microdeletion syndromes (and of course such classic conditions as
Down syndrome). With the advent of microarray analysis, new syndromes
came to be identified based on their DNA aberration, a “genotype-first”
approach. Representative examples of these newer syndromes are
reviewed in Chapter 14.

SEX CHROMOSOMAL ABNORMALITY

Sex chromosome (gonosome) imbalance has a much less deleterious effect
on the phenotype than does autosomal aneuploidy. The X chromosome is
one of the larger and is gene-dense; the Y is small, comprising mostly
heterochromatin, and carries very few genes. In both male and female,
one, and only one, completely functioning X chromosome is needed. X
chromosomes in excess of one are inactivated, as the normal 46,XX
female exemplifies; her second X does, however, maintain some segments
genetically active. With X chromosome excess or deficiency, a partially
successful buffering mechanism exists whereby the imbalance is
counteracted, in an attempt to achieve the same effect as having a single
active X. In such states as, for example, XXX, XXY, XXXX, XXYY, and
XXXXX, excess X chromosomes are inactivated. In the 45,X state, the
single X remaining is not subject to inactivation. If an abnormal X
chromosome (e.g., an isochromosome, or a deleted X) is present, then, as a
rule, cells containing this abnormal chromosome as the active X are
selected against, perhaps due to preferential growth of those cells in which
it is the normal X that is the active one. In X imbalance, the reproductive
tract and brain are the organs predominantly affected. The effect may be
minimal. As for Y chromosome excess, such as XYY, there is a rather
limited phenotypic consequence, but again the brain may be a vulnerable
organ.

FUNCTIONAL IMBALANCE
A correct amount of chromatin does not necessarily mean the phenotype
will be normal. Inappropriate inactivation, or activation, of a segment of
the genome can compromise the genetic message. Some segments of the
genome require only monosomic expression, and the homologous segment

25
on the other chromosome is inactivated. If this control fails, both segments
can become activated, or both inactivated, and the over- or under-
expression of the contained loci can cause phenotypic abnormality. The
classic example of this is genomic imprinting according to parent of origin,
and we discuss this concept in Chapter 18. A rather specialized example
arises with the X-autosome translocation. A segment of X chromosome
can fail to be inactivated; or conversely, X-inactivation can spread into an
autosomal segment (Chapter 6).

The Frequency and Impact of Cytogenetic Pathology

According to the window of observation, chromosomal disorders make a
greater or lesser contribution to human mortality and morbidity. Looking
at prenatal existence, the earliest window has been provided by the in vitro
fertilization (IVF) clinic, from the procedure of preimplantation genetic
diagnosis (Chapter 22), at which cells taken from 3- to 5-day-old embryos
are subjected to genetic analysis; and an extraordinary fraction are
chromosomally abnormal. After implantation (about day 6), and through
the first trimester of pregnancy (to week 13), chromosomal mortality is
very high, and aneuploidy is the major single cause of spontaneous
abortion (Chapter 19). Perinatal and early infant death has a significant
chromosomal component, of which trisomies 18 and 21 (although the
latter less so in more recent times) are major elements.
As for morbidity, the brain, as mentioned above, is the most vulnerable
organ, and chromosomal defects are the basis of a substantial fraction of
all intellectual deficit, and many of these retarded individuals will also
have structural malformations that cause functional physical disability.
Among a mentally retarded population, Down syndrome is the
predominant contributor in the fraction who have a classic chromosome
abnormality (Phelan et al. 1996). Development of the heart is particularly
susceptible to chromosomal imbalance, and in a population study from the
US National Center on Birth Defects, 1 in 8 infants with a congenital heart
defect had a chromosomal abnormality, with again trisomy 21 the most
common of these (53%), followed by trisomy 18 (13%), 22q11.2 deletion
(12%), and trisomy 13 (6%) (Hartman et al. 2011).
Adolescence is a period during which many sex chromosome defects
come to light, when pubertal change fails to occur; and in young
adulthood, chromosomal causes of infertility are recognized. Few new
classic cytogenetic defects come to attention later in adult life, but many

26
retarded children survive well into adulthood and some into old age, and
some require lifelong care from their families or from the state. This latter
group imposes a considerable emotional and financial burden. While some
parents and caregivers declare the emotional return they have from looking
after these individuals, for others this responsibility is a source of
continuing, unresolved, if attenuated, grief.
In Table 1–1 we set out the birth incidences of the various categories of
(classical) chromosomal abnormality; these data are from a Danish study,
one of a number that have examined this question in the later decades of
the twentieth century, with largely similar findings in each. Overall,
around 1 in 135 liveborn babies have a classical chromosomal
abnormality, and about 40% of these are phenotypically abnormal due to
the chromosome defect. If we were to look at day-5 blastocysts, the
fraction with abnormality might be close to a half. Fertile adults
(ascertained by virtue of having presented for noninvasive prenatal testing)
have much lower frequencies of sex chromosome aneuploidy (Samango-
Sprouse et al. 2016). If we studied a population of 70-year-olds, we could
expect to see very few individuals with an unbalanced autosomal
karyotype.

Table 1–1. Classical Chromosomal Rearrangements and Imbalances,

Recorded in 34,910 Live Newborns in Århus, Denmark, over a Total
13-Year Period, 1969–1974 and 1980–1988
BIRTH
NO. OF PER FREQUENCY
CASES 1,000a PER GROUP
Sex Chromosomes
Klinefelter Syndrome and Variants
47,XXY 20 1.12b
47,XXY/46,XY 7 0.39
46,XX 2 0.11
1 in 616 ♂
XYY
47,XYY 18 1.01
47,XYY/46,XY 2 0.11

27
 1 in 894 ♂
XXX
47,XXX 17 1.00
1 in 1,002 ♀
Turner Syndrome and Variants
45,X 1 0.06
45,X/46,XX and 45,X/47,XXX 3 0.18
45,X/46,X,r(X) 1 0.06
45,X/46,X,i(Xq)/47,X,i(Xq),i(Xq) 1 0.06
Other Turner variant 2 0.12
1 in 2,130 ♀
Other
45,X/46,XY 1 0.06
46,XX/47,XX,del(Yq) 1 0.06
46,XX/46,XY 1 0.06
Total 77 2.21 1 in 453
Autosomes
Unbalanced Forms
Trisomy 13 2 0.06
Trisomy 18 7 0.20
Trisomy 21 51 1.46
Trisomy 8 1 0.03
Supernumerary marker, ring 25 0.72
Deletions, duplications 6 0.17
1 in 379
Balanced Forms
Robertsonian 13/14 translocation 34 0.97
Other Robertsonian 9 0.26

28
Reciprocal translocations 50 1.43
Inversions (other than of 4 0.11
chromosome 2)
1 in 360
Combined sex plus autosomal 266 7.62 1 in 131
totals
Combined totals, excluding 169 4.84 1 in 207
balanced autosomal forms
Notes: Not included in the 34,910 live newborns listing are four cases of induced
abortion due to sex chromosome prenatal diagnosis, involving the karyotypes
47,XXY, 47,XYY, 47,XXX, and 45,X/46,X,del(Xq), and 15 cases of autosomal-
diagnosis induced abortions, involving the karyotypes +21, +13, +18, and three
different derivative chromosomes. Had these pregnancies proceeded to term, the
frequencies in the relevant group category would have been marginally increased.
These figures might continue to be broadly valid into this century, except that
the category of deletions and duplications will substantially increase due to the
more powerful detection now offered by molecular technology.
a
Per 1,000 male, per 1,000 female, or per 1,000 both, as appropriate. The
gender-specific denominators in this study were 17,872 males and 17,038 females.
b
An increasing incidence of XXY in recent years has been suggested, and an
Australian study, including data up to 2006, arrived at a figure of 1.91 per 1,000
(Herlihy and Halliday 2008; Morris et al. 2008; Herlihy et al. 2010).
Source: From Nielsen and Wohlert (1991)

The finer the cytogenetic focus, the greater the incidence, and it is now a
task for the cytogenetic epidemiologist of this century, in the
microarray/molecular era, to derive new estimates of cytogenetic
abnormalities in the different populations (Rosenfeld et al. 2013). The
brain again declares its susceptibility, with many examples of a brain-only
phenotype (intellectual disability, epilepsy, autism, psychiatric disease)
due to microduplications and microdeletions detectable only on molecular
karyotyping, and chromosomes 15 and 16, in particular, represented.

THE RESEARCH APPLICATION OF CYTOGENETIC

PATHOLOGY
The phenotypes that result from chromosome abnormalities can point the

29
Another random document with
no related content on Scribd:
us little ones it was, too. After a heavy downpour of rain the poorly
paved street and the low, marshy neutral ground was often flooded
clear across from sidewalk to sidewalk. It was great fun to watch the
men trying to cross the street after one of these rains. Rubber shoes
were unknown, so men depended on high boots. Of course, ladies
did not venture forth at such times, when they required more
protection for the foot than a thin-soled slipper afforded. There were
goloshes, wooden soles fastened with straps and buckles over the
instep. A golosh looked like a roller skate and was about as easy to
walk with. You never see one now.
I wonder if anyone under seventy-five years of age passes old
“Julia Street row” to-day and knows that those “13 Buildings”
between Camp and St. Charles Streets have an aristocratic past,
and were once occupied by the leading social element of the
American colony residing in the early forties above Canal Street? “13
Buildings” it was called, and at that date, and a decade later, every
one of them was tenanted by prominent citizens of New Orleans.
There they lived and entertained a host of delightful guests, whose
names were a power then, but whose descendants are perhaps little
known to-day.
There lived Mr. Lanfear with his two daughters. Louisa later
became the wife of David Ogden. There lived Mrs. Slocomb and her
three children. They became Mrs. T. G. Richardson, so well known
and honored to-day in the Crescent City; Mrs. David Urquhart, now
living in England, and Capt. Cuthbert Slocomb. Late in the forties
that family went to Europe, and returned to occupy the house, built in
their absence, which is now the home of Mr. Frank Howard, opposite
Lafayette Square.
The Branders—Mr. Brander was a merchant of some note and
social standing. His daughter, Caledonia, married Mr. Sager, an
Englishman, and eventually went to Europe. Virginia Brander
became the wife of Edward Matthews, a New York man, who
subsequently made a large fortune by speculating in long leases of
valuable business sites in New York during a panic in commercial
circles at the time of the Civil War. Their son, Brander Matthews, is a
distinguished man of letters and professor in Columbia College. The
Smith family, a host of handsome girls, occupied the house next to
the Camp street corner, and in that house the original J. P.
Labouisse married beautiful Dora Smith, whose death, at the
advanced age of ninety, occurred a short time ago. Charles
Cammack married Sarah Smith in the same house, and Mary Smith
married Morris, the son of Beverly Chew, who was a defendant in the
noted Gaines case of that day.
H. S. Buckner’s home was midway of the row, and there was born
Ellen Buckner, who became the wife of James B. Eustis, the first
United States ambassador to France. Those old friends who visited
Paris in her régime tell of her cordial and gracious hospitality.
Leonard Mathews lived in one of the “13 Buildings.” He was agent
of the Sun Insurance Company. There were young people in that
house, too. Mary Jane Mathews married Mr. Hugh Wilson, a
prominent business man, and their daughter married Lyman Josephs
of Rhode Island. There was also the family of Dr. William Kennedy.
Mrs. Kennedy was sister of Mr. Levi Peirce and of Mrs. Hillary
Cenas. Their daughter, Charlotte, married a son of the distinguished
Sargent S. Prentiss of Mississippi.
 Henry Clay

Diagonally across the corner of Julia and St. Charles Streets was
the home of Col. Maunsel White, a veteran of Chalmette, who won
his title on the field. A genial Irishman, his serenity was disturbed
about the time of which I write by the elopement of his oldest
daughter, Eliza, with the dashing Cuthbert Bullitt. She died many
years ago, but Mr. Bullitt lived and dashed many years after dashing
ceased to be becoming. A short time ago he also passed away at a
ripe old age, having survived every contemporary.
My personal recollections of the guests who came to my father’s
house in “13 Buildings” are distinct. Henry Clay, a lifelong friend of
father’s, the only one I ever heard call him “Dick” (even my mother
did not do that), was a frequent visitor whenever he came to the
Crescent City.
My father planned in 1844 to go to England, and his old friend
gave him the following letter. It was never delivered, owing to the
enforced abandonment of the plan, and hangs now on my library
wall, framed, beside the Henry Clay portrait which illustrates this
book and which is by far the best likeness I have ever seen of
Kentucky’s gifted son.

Ashland, 16th July, 1844.

My Lord:
Richard H. Chinn, Esq., who will deliver this letter desiring
the honor of your Lordship’s acquaintance, I take pleasure in
introducing him (sic) to you as an eminent and highly
respectable councillor at law, now residing in New Orleans,
whom I have long known.
I avail myself of the opportunity to assure your Lordship of
the constant esteem and regard of
Your Lordship’s faithful and obedient servant,
H. Clay.
The Right Honorable Lord Ashburton, London.

Gen. E. P. Gaines and his tiny, frisky wife, the noted Myra Clark
Gaines, were also frequent guests. The General, a warrior, every
inch of him, very tall, erect and pompously stately, always appeared
at “functions” in full uniform, epaulettes, sword and what not, while
she, all smiles and ringlets and flounces, hung upon his arm like a
pink silk reticule. There also came Charles Gayarré, the Louisiana
historian; John R. Grymes, the noted lawyer; Pierre Soulé, diplomat;
Alec Bullitt, Alec Walker and George W. Kendall—all three editors of
the leading paper of the day, the Picayune. And so on, including a
host of others just as noted and interesting in their day, whose
names are never mentioned now. I cannot omit mention of the
famous wit and beauty, Miss Sally Carneal, niece of the original Nick
Longworth, of Ohio, for, with her superb voice, she frequently
entertained and entranced my father’s guests. I recall one occasion
when she sang, with inimitable pathos and wild passion, a song I
never wish to hear again, “The Maniac.” The little audience, roused
to a pitch bordering on madness, was almost ready to shriek and
tear its hair. Glendy Burke (does anybody remember him? He was
an eligible parti then) fell in desperate love with her that night, and
subsequently they married. All are gone now; and most of them
forgotten, except, possibly, by an old lady, who sits at her fireside,
and unfolds the book of memory....
In course of time a Mme. Peuch took possession of the house on
the St. Charles street corner, and, horrors! opened a boarding
house, whereupon the aristocratic element gradually fluttered away.
The Smiths and Labouisses went, as we thought, into the
wilderness, up Carondelet Street to a kind of country place, with lots
of ground and fig trees. The Buckners flew still further. I think they
halted at Jackson Street—I am not sure the street had as yet a
name. The Mathews moved to Annunciation Street. My father took
his lares et penates to Canal Street, and Mrs. Slocomb still further
away, to Europe. The infection spread, and in a short time the whole
“13 Buildings” pimpled out into cheap boarding houses or rented
rooms. Sic transit! Where are all those fine people now? And what of
the “13 Buildings”? Do they still stand and flaunt their signs over the
places once adorned with immaculately shining brass name plates?
or have they, in the march of events, also silently departed, and left
places to be filled by a newer generation of buildings, in imitation of
the lords of the earth that knew them and loved them and patronized
them in their heyday?
 XXIV
“OLD CREOLE DAYS” AND WAYS

It was in the autumn of 1846 La Belle Creole carried me, a young

girl, to Dr. Doussan’s home, on the coast, above New Orleans. I was
sent there to learn to speak French, which I had been fairly well
taught to read and write. Both Dr. and Mme. Doussan were past
middle life. The doctor was a native of France, madame a Creole,
and the few arpents they owned were her inheritance. Their home
was surrounded by a settlement of Creoles, pure and simple
Creoles, such as I doubt exists to-day in the changed conditions that
seventy years bring.
The simple natives, who had little patches, some of which
amounted to little over an arpent (about an acre), were domiciled so
conveniently near that it afforded an unending source of interest to a
wide-awake American girl to see, listen to, and talk with them. They
were not “poor folks” except possibly in the one meaning of the term.
There was a family of Grandprés in that little settlement. Hearing the
name Grandpré would instantly call to mind the Grandprés of
Louisiana’s early days. Was not a Grandpré Governor, or Captain
General, or something else as notable and commanding in Louisiana
history, in the French, or more likely Spanish, occupancy of the
country? This family descended from the original proud stock. The
children, grown, half-grown, babies, at the time of which I write
actually had a resident tutor, M. Marr, a man of no mean ability. I do
not know how far they advanced in other branches of education, but
their beautiful chirography would put to the blush any college
graduate who hovers around our young girls to-day, and they signed
themselves, too, with a grand flourish, De Grandpré. My old red and
gilt album (every girl had an album and her friends wrote fulsome
nonsense in it) has a “Je suis très flatté, mademoiselle, de pouvoir
m’inscrire,” etc. signed L. De Grandpré. Looks as if I had flattered a
nobleman of France! Doesn’t it?
That flock of children of all ages and sizes were being educated
well for their day and generation, albeit Grandpré mère strolled about
in a gingham blouse volante, her frosty hair covered with a plaid
tignon; and Grandpré père sniffled around (he had some catarrhal
trouble, I guess) in carpet slippers. I do not think he ever did
anything but bear the high-sounding name, and I never heard, after
those album days, that the sons did either.
A family of Lafitons lived so near that we heard their parrot
screaming for “mon déjeuner” every morning, long before it was time
for anybody’s breakfast. I think the bond of friendship that existed
between le vieux Lafiton and Dr. Doussan must have been that they
came from the same province in France. Most nights, Sundays as
well, “mon voisin,” as the doctor called him, came for a game at
cards. Long after my supper was served on a tray, and I was safely
tucked into bed, madame presided at a banquet of gumbo,
jumbalaya and salad, with their beloved Bordeaux, which was
spread for the old gentlemen. Lafiton had straggling locks of white
hair, falling over the collar of his great coat, reminding me of the
picture of Little Nell’s grandfather, and the home of the Lafitons
carried out the simile, for it was as melancholy and cheerless as any
“Old Curiosity Shop” could be. There were two bright, capable girls in
it, though, who never knew or saw anything better than the rickety
old house, way up on stilts, that they lived in. There they stitched and
darned and mended and patched all day (Creole women are not
lazy), and managed to make a creditable appearance for an
afternoon promenade on the levee.
The two grown sons caught driftwood and fish, and when they
tired of that exertion made crawfish nets. (En parenthèse, when I
had a fifteenth birthday, Pete, the long-legged one, gave me a finger
ring he had made of the tooth of a shell comb.) They did not own a
skiff, much less a horse or voiture. For ever so long I thought Mme.
Lafiton had chronic toothache, or some trouble in her jaws, for she
always wore a handkerchief over her head, tied under the chin, and
also a look of discomfort. In time I discovered that style of
headdress, and that troubled smile, were peculiarly her own, and did
not signify anything in particular.
We had other neighbors less picturesque than those I have
mentioned. Madame had a cousin living quite near, who had, as had
all Creole women in those days, a great flock of children. The
Dubroca family seemed to be fairly well-to-do. Mr. Dubroca was
sugar-maker for a nearby planter. Madame and her daughter Alzire
were thrifty, hospitable and kindly. The sons, as they grew up, were
sent to schools and colleges. Madame was a sister of Mrs. (Judge)
Eustis of New Orleans, both being daughters of Valèrie Allain, a
planter of means, whose property when divided among his children
did not amount to much for each.
That brings me to the Favrot family. Judge Favrot was a prominent
citizen of the parish, and his son, a law student when I knew him,
was much above the average. I scarce should mention this family
that I saw almost daily and knew so well in connection with the
obscure Creoles of the simpler life that I met and knew quite as
intimately. The judge, and his son, were violinists. It was no unusual
thing for him to play dance music for us, accommodating old
gentleman that he was! We always had to adjourn to Lafiton’s to “trip
the light fantastic,” for there was a great barn of a room, with bare
floor, and no furniture to mention, which they called le salon.
Mme. Doussan often visited friends, by rowboat, on the opposite
side of the river. She felt the responsibility of the care of the young
girls, so strangely placed in her hands, so she never embarked on
her frequent visits by boat or voiture without the company of one she
might have esteemed an incumbrance if I had not already been
received into the holy of holies of her loving heart.
There were two families of Choppins we saw frequently. The
daughter of one, quite a child then, became at a later date wife of
Dauphin. The eldest son of the other Choppin family, a youth of less
than twenty, was already studying medicine in the office of a country
town doctor. We saw much of him, the bright, attractive fellow! as he
used to row himself over to the impromptu dances in the Lafiton
salon. Later his ambition carried him to Paris, and later still he
returned, a distinguished physician and surgeon, to New Orleans. He
was a devoted citizen also. None who heard his impassioned
address, and his rendering in thrilling tones the inspiring “Aux Armes!
Citoyens” of the Marseillaise from the steps of Clay’s monument, on
Canal street, at the beginning of the war, ever forgot it.
Madame and I often visited other families in Baton Rouge, the
Bonnecazes, Lanoues, Huguets and so on. As I remember, all lived
over or in the rear of their shops. Very many families lived over
shops in those days, not always over their own shops either. John
Winthrop, a scion of the Massachusetts John Winthrop, and his
aristocratic family lived over Symes’ lace store, on Royal street in
New Orleans. There was a shoemaker’s establishment on the
ground floor of the Miltenberger residence. My father’s family lived
over an exchange broker’s office on Canal Street. In 1842, when a
mob raided, or threatened to raid, banks and exchange brokers’
offices, the strong box of the firm in our basement was conveyed to
my mother for safekeeping. But this was in New Orleans, and I see I
am wandering from my Creole friends on the coast, where I
delighted to visit with ma chère madame.
Twice during that lovely six months’ episode of my life, escorted by
the doctor, we boarded the fascinating Belle Creole and made longer
flights and longer visits to relatives of madame living beyond a
voiture’s possibilities. Once it was to spend a few days with the
Valcour Aimes at their incomparable home; at another time we had
two never-to-be-forgotten days at Sosthène Allain’s, where I met two
sweet girls of my own age. Then and there began a friendship that
continued through our young ladyhood. We were three inseparable
companions until three weddings sent us (as is the nature of things)
on divergent paths. Celeste went to Paris, so remote then that she
was practically lost to us. I do not suppose a single one of those who
made those six months of my girlhood so happy is living to-day.
Some have left no descendants; I do not know who has or who has
not, but I pay this tribute to the Creole simple life, that seems in the
retrospect almost ideal, and no episode of my checkered life is
sweeter to recall.
 Dr. Doussan was a botanist. His garden was the mecca of all
lovers of plant life. I imagine it was excelled only by the noted
grounds of the Valcour Aimes. Fruit and vegetables were sent daily
in a skiff to the town market. Ma chère madame, in her black silk
blouse volante and her cap, with stiff, fluted frill tied under the chin,
often let me help her make the formal little bouquets for the market,
the dear old stiff bouquets, flat as a plate and nestling in a frill of lace
paper! The doctor spent hours in his cabinet with his botanical
treasures. Daily I was summoned to read to him his Paris Journal,
and to write a composition. No teacher could have been more
painstaking; no scholar more appreciative.
Early in 1847 a nephew of the doctor’s arrived from France, a
dapper, Frenchified youth of eighteen. The Doussans were childless,
but they had adopted a young girl. At the time of which I write she
was about my age, and was being educated at Sacré Cœur
Convent. She was home only for Easter vacation. No one told me,
no one even hinted it, but I intuitively understood that a mariage de
convenance was planned for the dapper young Frenchman and the
pretty blonde girl, and the visit was meant to introduce Marie to her
prétendu; they seemed to accept the arrangement complacently, but
I was most interested in watching the proceedings, and, to say the
least, much entertained.
It was fully fifty years after these events when Doussan neveu and
I met again, two old gray-haired folks. When the first frost of
astonishment melted, and we could recognize each other, we had a
grand time recalling places and people. How we laughed over the
remembrance of the antics of the doctor’s pet monkey; and, oh yes!
the voluble Lafiton parrot! For a brief hour we lived again the halcyon
days of fifteen and eighteen. The following year Doussan passed
away—severing for me the last living link that bound me to the
simple Creole life, on the borders of which I had such a happy
girlhood.
 XXV
A VISIT TO VALCOUR AIME PLANTATION

La Belle Creole! That name will bring a smile, mayhap a tear, to

your grandmother, so many sweet reminiscences of her young
girlhood may be associated with the little coast packet that carried
her a-visiting from New Orleans to plantation homes in “the days that
were,” those leisurely days when there were no rail cars tearing and
crashing over the land, no express companies to forward packages,
no common carriers of any sort. A boat like La Belle Creole was a
necessity. On her trips she stopped at every little town and country
post office, like Brusle landing and Lobdell’s store; answered every
signal and every hail, shuttling across the river, back and forth,
touching here for a keg of sirop de batterie, a hamper of oranges;
touching at the very next plantation to take in somebody’s carpetbag
or put ashore somebody’s darky, Capt. Ure always at his post on
deck to expedite every move. La Belle Creole was not a freight boat,
but a passenger packet, par excellence. There were boats galore to
handle freight, but only one Belle Creole! “Steamboat ahoy!” We
slow up, a gentleman rushes down from his plantation house,
followed by a darky, carpetbag in hand. A plank is quickly run out,
touching the shore, steadied by deckhands; passenger rushes
aboard, has a handshake with Capt. Ure, and away we go to
perhaps another hail. In the cabin the scene is like that of an
“afternoon tea,” an “at home,” a “reception,” whatever you will, for
everybody knows everybody, and everybody shakes hands with
everybody, and thus the newcomer is welcomed to the social
atmosphere of a circle of Creole friends. “Comment ça va?” “Aye!
quel chance! c’est toi,” are heard on every side, for some of these
people rarely meet except in transit. And so, we sail along; the
simple little craft is glorified by the magnetic influence of its
passengers.
 M. Champomier is on board. Everybody knows le vieux
Champomier. He mingles with all, conspicuously carries his
memorandum book and pencil, and we all know he is “on business
bent,” getting from any and every available source statistics of the
year’s crop of sugar. Whether he acted for a corporation, or it was
his individual enterprise, I never knew, but he visited the planters,
traveled up and down and all around the sugar region, and in the
spring compiled and computed and published in a small, paper-
covered book (price $5) the name and address of every planter and
the amount of sugar made on each individual estate. “Champomier’s
report” was considered as authentic as need be for the planter to
know what his neighbor’s crop actually amounted to, and the city
merchant to adjust his mortgages and loans on a safe basis.
It was after midnight when the plank was thrown out to touch the
levee of the Valcour Aime plantation; midnight in late March, 1847.
Deckhands steadied the wabbling plank till three persons and their
little baggage were safely landed ashore. A tram (as it is called to-
day) was awaiting the doctor, Tante Lise and myself, then a girl of
fifteen. Darkies with torches preceded and followed us to the house,
not so far away, only a short walk, but Tante Lise must not be
permitted to walk at that hour of the night. The tram was nothing
more than a flat car, fitted for the occasion with seats, on a short
railroad leading to the sugar refinery, which I believe was the first in
the state. A dusky housekeeper received us at the house. Not
knowing at what hour we might appear, the family had retired. Belle
Creole, as may be supposed, had no fixed schedule of arrivals or
departures. Fires were already alight in our rooms, affording a
cheery welcome. Before we were ready for bed basins of hot water
were brought for the inevitable foot bath of the Creole. Something
warm to drink, a tisane probably—I remember I thought it might be
ambrosia, fit for the gods, it was so deliciously refreshing. Then I was
tenderly tucked into bed, and told to “dormez bien,” which I
straightway proceeded to do.
The sun was already proclaiming a bright spring day when I
inhaled the odor, and opened my eyes to a full-blown rose on my
pillow; and gracious, how good! a steaming cup of café au lait. On
our descent to the breakfast room we received an effusive and
cordial greeting from M. and Mme. Valcour, and their daughter
Félicie, a girl of my own age. The air was redolent of the delicious
odor of roses, the windows open to the floor upon the garden, the
floor of the room not one step higher than the garden walks. The
Valcour Aime house was a two-story structure. The long, main
building faced, of course, the roadway and the river; there was a
long L at each end, running back, thus forming three sides of a
square court. A broad and partly jalousied balcony extended entirely
around the three sides of the building, fronting the court. This
balcony afforded the entrances to a seemingly endless series of
living and sleeping rooms, the whole house being, so to say, one
room deep only. The first floor, flush with the ground, was entirely
paved with square blocks of stone or brick. There were to be found
the small and the grand dining rooms, the master’s office and den
and the various and sundry domestic departments. The salon
opened on the second floor balcony. The paved court below was
protected by the deep balconies and an awning. The assemblage of
all the family and the favorite resort of their multitudinous guests,
madame’s basket, mademoiselle’s embroidery frame, the box of
cigars, the comfortable lounging chairs, were to be found in that
entrancing court.
M. Valcour, tall and graceful, was at that time in the prime of life,
and was my (romantic) ideal of a French marquis; Mme. Valcour,
inclined to embonpoint and vivacious, kissed me and called me “ma
petite,” though I was quite her height. But the charm of my visit to
that incomparable mansion, the like of which is not to be found on
the Mississippi River to-day, was the daughter, Félicie, who at once
took me under her wing and entertained me as only a well-bred
young girl can. She showed me all over the premises, opening door
after door, that I could see how adequate the accommodations for
the guests who frequently filled the house; into the salon that I might
see and listen to the chimes of the gilt clock Gabie had sent from
Paris. Gabriel Aime, the only son, was then in Europe. Sweet Félicie
never tired of talking of Gabie and showing me the pretty trifles from
abroad (so far away then) he had sent home from time to time. She
sent for the key, and opened the door of Gabie’s room, that I might
see how he had left it, and, “Mamma won’t have a thing changed;
she wants him to find his gun and boots and cap just where he left
them.” Girl-like, she confided to me that she would be a young lady
when Gabie came, and they would have a house in the city and a
box at the opera, for Gabie loved music.
By this time a number of the Roman family arrived. M. Valcour’s
oldest daughter had married Gov. Roman’s son, and a flock of
Roman grandchildren came with their parents to welcome the doctor
and Tante Lise, and incidentally the young girl with them. The
Valcours and Romans were closely related, independent of the
marriage of their children. Both families being related to Tante Lise
also, there was a great reunion and rejoicing when the tante made
her annual visit. The governess, a New England woman, was
accorded a holiday, in which Félicie participated. Years after,
perhaps as many as forty years, I met and renewed acquaintance
with that governess in her New England town. Only recently she
passed away, having outlived, I understand, all the little pupils who
clustered around “Dear Miss Goddard.”
Félicie and I, with a whole escort of followers, explored the
spacious grounds, considered the finest in Louisiana. There was a
miniature river, meandering in and out and around the beautifully
kept parterres, the tiny banks of which were an unbroken mass of
blooming violets. A long-legged man might have been able to step
across this tiny stream, but it was spanned at intervals by bridges of
various designs, some rustic, some stone, but all furnished with
parapets, so one would not tumble in and drown, as a little Roman
remarked. If it had not been before Perry’s expedition to Japan, at
any rate before his report was printed and circulated, one might have
supposed M. Valcour received his inspiration in landscape gardening
from the queer little Eastern people. There were summer houses
draped with strange, foreign-looking vines; a pagoda on a mound,
the entrance of which was reached by a flight of steps. It was an
octagonal building, with stained-glass windows, and it struck my
inexperienced eye as a very wonderful and surprising bit of
architecture. Further on was—a mountain! covered from base to top
with beds of blooming violets. A narrow, winding path led to the
summit, from which a comprehensive view was obtained of the
extensive grounds, bounded by a series of conservatories. It was
enchanting. There I saw for the first time the magnolia frascati, at
that date a real rarity.
Another day, doctor, Tante Lise, Félicie and I were rowed in a skiff
across the river to Sacré Cœur Convent to see tante’s adopted
daughter, Marie. I recall spending the day there, the kindly nuns
showing the little heretic all through the building, and being rowed
back to the plantation at sunset.
Next morning the Belle Creole was due, and our visit to fairyland
was drawing to a close. The call, “la Vapeur,” rushed us to the
landing in the tram, the “whole pack in full cry” of the Roman children
running by the side and calling adieu to dear Tante Lise. We gingerly
walked the plank, in single file. The boat backed out to get her
leeway, and once more for a moment we were in full view of the
house. Two figures fluttered handkerchiefs from the balcony, Mme.
Valcour and Félicie waving a last adieu—alas! a last. On entering the
cabin, behold the ubiquitous M. Champomier, with his everlasting
book and pencil. As he greeted the doctor I heard (in French, of
course), “Can you tell me the exact amount of——?” I fled, and at
the rear end of the boat I had one more last glimpse of Valcour
Aime’s plantation. Alas! the last.
A month later I was on a clipper ship, the Silas Holmes, bound for
a New England school. That Yankee, Silas Holmes, was a transport
during the war, and like many a war relic has long been out of
commission, if not out of existence. And the dainty Belle Creole,
gone too! like thousands of Belles Creoles of her day and date.
Dear Félicie married Alfred Roman, adding another link of
relationship to the Roman and Valcour Aime families, and the adored
and only son, Gabriel Aime, died (I think Tante Lise wrote me)
abroad.
I should like to know. No, I do not want to know. I already know too
many wrecked homes and vanished fortunes and broken hearts. I
want always to think of the Valcour Aime home and its charming
hospitality, as I saw it and knew it, and loved it more than sixty years
ago, when I waved a last adieu—alas! a last.
 XXVI
THE OLD PLANTATION LIFE

It is almost a half century since the old plantation days. Only those
who number threescore years and ten have a personal
remembrance of the cares, duties and pleasures of the old plantation
life. Only those who bore the cares, discharged the duties and
prepared the way for the pleasures really understand the life that
died and was buried fifty years ago. People who know so much
about that fanatic John Brown and the fantastic “Uncle Tom’s Cabin”
are asking what one fought and bled for (did he bleed?) and what the
other was written for. Some of those inquiring souls are over fifty
years old, and what is more, their fathers were slave owners. The
few of us tottering around who can tell of the old plantation life are
threescore years and ten, and if we do not hasten to tell the story it
may never be told. It is well to leave a record of a life that has
passed beyond resurrection, a glorified record it may appear, for as
we stand beside the bier of a loved and lifelong friend, we recall only
his virtues. So as I look back on the old plantation life only the
comforts and pleasures troop before me. It had its duties, but they
were not onerous; its cares, but they were not burdensome, nor were
its pleasures excessive. What we planned and accomplished for our
slaves afforded us more satisfaction than any man of the present
day can feel for his grand stables of hunters and roadsters and
racers, that absorb his time and means....
Booker Washington, in that very interesting volume, “Up from
Slavery,” tells of his early life when his mother (he never knew his
father, and thinks he was a white man) was the slave of a well-to-do
Virginia farmer, and the slave quarters had dirt floors. That may have
been in the clay hills of Virginia, but I never saw a cabin, unless it
was a pig pen, with a dirt floor. I am no apologist for slavery; the
whites suffered more from its demoralizing influence than the blacks,
but we were born to it, grew up with it, lived with it, and it was our
daily life. We did well by it; no people could have done better. It is
past now. When I tell of my own home it is to tell of the plantation
homes of everybody I knew. We did not differ or vary to any extent in
our modes of life and management.

Arlington Plantation on the Mississippi.

Slaves were comfortably housed. Their cabins were elevated

above the ground, two rooms in each building, a chimney between, a
porch in front and windows on two sides. The slaves were well fed
and well clothed in osnaburgs and linseys cut and made in the
sewing room of the “big house.” Though the hook worm theory was
not at that time exploited they were well shod. There were drones; I
guess there were hook worms too, but we did not know it. The old
and infirm had light tasks. Men pottered around the woodpile, or
tended the cows on their promenades over the levee, and the
women sewed a little and quarreled, as idly disposed old folks will,
among themselves (we who visit almshouses now know how that is)
or fussed with the frolicking children. I never saw in those days a
negro with spectacles, or one who seemed to need them.
There was an infirmary for the sick, and a day nursery for the
babies, under the charge of a granny, a well-ventilated room with a
spacious fireplace, where pots and kettles were always on hand,
mush and herb teas always on tap; there the babies were deposited
in cribs all day while the mothers were at work in the fields. No
woman went to work until her child was a month old. A large diary
folio record was kept by the overseer of all the incidents of the
plantation; when a woman was confined, when she was sent again
to the field, who was ill in the hospital, if doctor was summoned, what
part of the canefield was being cultivated day by day, when sugar-
making began, when finished, what the yield of the various “cuts,”
how many hogsheads and barrels of molasses shipped and by what
boats; all these items and ever so many more were recorded. A
doctor was employed at $600 per annum. He came only in extreme
cases. Headaches and stomach aches, earaches, toothaches and
backaches, all these minor ills came under the care of the overseer
and “Gunn’s Domestic Medicine,” a formidable volume of instruction.
The lady, the “mistis” of the big house, made frequent visits to the
quarter lot, saw that things were kept tidy and ministered to the sick.
We did not have “made-over” dishes, cold meats nor stale bread
on our tables; little darkies were sent by the half sick and aged for
“left overs.” Children were not bottlefed or spoonfed; they consumed
pot liquor and mush and molasses as soon as they were weaned.
Corn, cowpeas and turnips were cultivated for the slaves, and when
there was an overplus of garden vegetables it was sent to the
quarter kitchen. Their meat was pickled pork—it was called “clear
sides”—shipped from Kentucky or Missouri. All their cooking was
done by two cooks in a big kitchen, but every cabin had a fireplace,
with a pot or skillet, of course, for we all know how the darky dotes
on little messes of her own doing. All the doors had locks, and the
women went to the field with the key hung around their necks.
Each spring at house-cleaning, cabins were whitewashed inside
and out; also the stables and other plantation buildings, the fences
and trees as high up as a long pole or brush could reach. From
Saturday noon till Monday was holiday, when the enterprising men
chopped wood, for which they were paid, and the drones sunned
themselves on the porch steps, and the women washed their
clothes. I knew of only one planter who made his negroes work on
Sundays. He was an Englishman who married into a plantation. The
indignant neighbors called the attention of the grand jury in that
case, with success, too. During sugar-making everybody worked day
and night, but the season was short, terminating in December.
I cannot recall more than three deaths in ten years. I have no
record to refer to (I guess that plantation folio afforded some
information to the Union army). There was a burial ground for the
slaves. One of them, the engineer, by the way, and a mighty good
negro, too, acted as preacher. He married and buried and in all ways
ministered to the spiritual needs of his flock. I recall teaching Lewis
to sing “Canaan.” He wanted to learn a hymn, and had a lusty bass
voice, while I did not have any at all. Lewis was not the only
accomplished negro. We did not have white labor. There were slave
carpenters, coopers, masons and sugar makers; women who cut
and made all clothing, shirts, coats, pantaloons, dresses.
By law no child under ten years of age could be sold from its
mother. I suppose that law is obsolete now! It happened a negro
child born in the penitentiary of a convict mother, named Alroy, had
to remain ten years in confinement; he was taught reading and
writing, probably all the Rs, by the convicts, while he imbibed in such
surroundings a good many less desirable accomplishments. Hon.
Mr. Alroy represented his native parish in the Louisiana Legislature
of reconstruction times. He was better fitted probably than some of
his dusky colleagues, for he could read the laws; some of them could
not. That is also of the dead past, thank God, and has no bearing on
the old plantation life, except as an illustration of the law regarding
slaves.
The “big house” had no fastenings on the front and back doors. In
the absence of my husband one time I was awakened, in the dead
hour of night, by a touch on my shoulder. “It’s me, mistis; de levee’s
broke.” A crevasse! Without taking time to put on an extra gown, I