Little Yellow Book About The Facts On Rare Chromosome Disorders

The
Little Yellow
PO Box 2189
Caterham
Book
Surrey CR3 5GN
England
Tel/Fax: +44 (0) 1883 330766
Email: info@rarechromo.org
Website: www.rarechromo.org
Unique would like to acknowledge the Sporting Bears Motor Club

for their support towards the publication of The Little Yellow Book.
Vol 1: A Guide to Rare Chromosome Disorders

by
Dr Beverly Searle BS C (H O N S ) P H D CB I O L MIB I O L and
Professor Maj Hultén P H D MD FRCP AT H
Rare Chromosome Disorder Support Group

Registered Charity Number 1110661
Registered in England and Wales Company Number 5460413
Registered Office: Valiant House, 3 Grange Mills, Weir Road, London SW12 0NE Issue 5
welcome to unique
Dear Parent,
Welcome to Unique. We hope that through membership
of the group you will feel supported in caring for your
very special child who has a rare chromosomal disorder.
Perhaps your child is still a baby or has passed the
baby stage but has only just been diagnosed. However
old your child, discovering that he or she has a rare
chromosomal disorder can come as a great shock. You
might be feeling a mixture of emotions; sadness,
confusion, numbness, anger, guilt, “why me?”, isolation
or bewilderment. Perhaps your reaction to your child
has surprised you. You might be feeling overwhelmed at
your lack of knowledge about your child’s condition or
despairing that your child’s condition hasn’t even got a
proper name. Whatever your feelings, rest assured that
other members of Unique, including the group’s
The Little Yellow Book, Vol 1
organisers, have experienced at least some, if not all, of
Published by
The Rare Chromosome Disorder Support Group
them. We know how much it can help to talk to people
who understand what you are going through and even
Rare Chromosome Disorder Support Group
Registered Charity Number 1110661 what you are talking about. You are not alone.
Registered in England and Wales Company Number 5460413
Registered Office: We have prepared this booklet to give you a basic
Valiant House, 3 Grange Mills, Weir Road, London SW12 0NE understanding of chromosomes and rare chromosome
Designed and printed by GREEN Gilbert disorders and to tell you a little bit about ourselves and
Written by Dr Beverly Searle BSC(HONS) PHD CBIOL MIBIOL the group. Please feel free to use the group’s services. If
and edited by Professor Maj Hultén PHD MD FRCPATH you have a question, we will do our very best to answer
Copyright © Unique – Rare Chromosome Disorder Support Group it or point you in the direction of someone who can.
2000
Very best wishes,
All rights reserved. No part of this publication may be reproduced in
any form whatsoever, stored in any retrieval system or transmitted in
any form or by any means without prior permission in writing from
the publisher.
ISBN 0-9541253-0-4
1
Telephone/Facsimile: +44 (0) 1883 330766 Email: info@rarechromo.org Website: www.rarechromo.org
contents history of unique
history of unique....................................................................................................3 Unique has been a source of mutual support and self-
help for families since it was founded by Edna
the unique team.......................................................................................................5 Knight in the UK in 1984 as the Trisomy 9 Support
Group. At that time, the group had just five member
consequences of rare chromosomal disorders..........12 families.
what can unique do to help?........................................................... 15 In 1989, with the support of the “In Touch Trust”
and “Contact a Family”, the group expanded to
all about chromosomes and genes............................................17 include families whose children have any rare
Cells, Chromosomes, DNA and Genes chromosomal disorder. In 1993 the group was
Chromosome Analysis granted charity status and the new logo Unique was
Symbols used in Karyotypes adopted.
rare chromosomal disorders..............................................................26 The group is run predominantly on a voluntary

NUMERICAL DISORDERS basis, mainly by parents of children with rare
Polyploidy chromosome disorders, using their own professional
Aneuploidy expertise but with the generous support of a number
STRUCTURAL DISORDERS of professional advisers. Unique has been funded
Translocations entirely by donations, covenants and fundraising
Balanced Reciprocal Translocations and activities. Membership is free but voluntary
Unbalanced Translocations donations are always very welcome. In January 1999,
Robertsonian Translocations Unique was awarded a 3-year grant by the National
Insertions Lottery Charities Board to fund a full-time
Deletions Development Officer. However, donations, Gift Aid
Rings and fundraising continue to be essential to fund all
Duplications other group activities like the newsletter and the
Inversions annual conference. Further funding for the Officers’
Isochromosomes and ESACs posts will be needed on an ongoing basis in order to
secure the future of the group.
further reading and information ................................................32 When, in April 1999, the Development Officer was
appointed, the group had just over 1100 member
donations, fundraising and covenants ...............................33
2 families. By January 2006, group membership had
risen to nearly 5000 families in 67 countries and
3
Telephone/Facsimile: +44 (0) 1883 330766 Email: info@rarechromo.org Website: www.rarechromo.org Telephone/Facsimile: +44 (0) 1883 330766 Email: info@rarechromo.org Website: www.rarechromo.org
continues to rise rapidly. The group also has many
professional members working in relevant fields,
such as genetics, medicine, nursing, the therapies
the unique team
and the allied professions like social work, education
etc.
Unique has adopted and works to an equal Unique has a voluntary Management Committee
opportunities policy and is registered under the Data comprising parents, grandparents and our Chief
Protection Act (registration number Z9206140). Medical Adviser, Professor Maj Hultén. The
committee supports the groups’ officers, who carry
out most of the day to day work. Let us introduce
you to some of the Unique team.
Edna Knight –
The Group’s Founder and
Co-ordinator
❝ Ifour
helped to establish Unique from the beginning. I have
daughters, two with a duplication of part of the
short arm of chromosome 9 - Wendy (17.7.65) and Julie
(26.10.71). My youngest daughter Claire (6.8.82) has a
balanced insertional translocation like myself, whilst
my second daughter Linda has normal chromosomes.
Wendy and Julie are doing well after very slow starts.
They have reading skills and are able to travel alone on
buses locally. Wendy attends a sheltered development
centre and goes out to large local companies and Wendy, Linda, Edna, Julie and Claire.
colleges for work experience. Julie works at the DSS,
with support from the Shaw Trust. I am pleased with
their progress so far and they are still progressing and
learning to do new things. Development continues even
in their 20s and 30s.
As coordinator, I keep a watchful eye on the progress of
Unique and liaise with committee members, without
whom the group could not run. With the employment of
Beverly Searle as Chief Executive Officer, a considerable
element of the burden of running the group has been lifted
from me. I am here to help with the smooth running of the
group and to encourage others. There are a great many
diverse activities within Unique such as coordinating the
compilation and dispatch of the thrice-yearly newsletter,
4 collating information for the annual conference and
working with many other members on various tasks.
5
Most importantly though I am here both to ensure that the better and I have met some wonderful people because of
organisation keeps to its own guidelines and to run a Jenny. As for Jenny, despite her disabilities, she is a
group that is both informative and sensitive to the needs delightful child and her sweet nature shines through.
of parents.
❞ I handle all the initial enquiries from new families and
professionals, making sure that we provide them with the
Beverly Searle – best information and ongoing support we can. Besides
line-managing our information team and being
Chief Executive Officer responsible for our databases, my major tasks include
❝ IApril
was appointed to the post of Development Officer in
1999 and in 2003 I was made Development
developing the services Unique provides, networking with
researchers and other support groups and raising the
Director. More recently I have become Chief Executive profile of rare chromosome disorders and the work of
Officer. I worked for Unique in a voluntary capacity for
some years as Database coordinator and was a member of
Unique among professionals and the general public.
❞
the management committee from the early 1990’s. I joined
the group shortly after the birth of my daughter, Jenny, in
Prisca Middlemiss –
February 1990. Jenny has a large deletion of the short Information Officer
arm of chromosome 18; she is profoundly learning and
physically disabled and has complex health needs. Jenny’s ❝ One of my earliest childhood memories is of my father
coming home from work and announcing that the
elder brother Jonathan has a mild heart defect, although
number of human chromosomes had at last been correctly
his chromosomes are normal. Before I had my children, I
counted. A Swede, Albert Levan, and an Indonesian, Joe-
Trevor, Beverly and Jenny. worked for many years as a research scientist, being
Hin Tjio, had overturned the prevailing wisdom that
awarded the degree of PhD for my research into aspects of
humans, like chimpanzees and gorillas, had 24 pairs of
the biochemistry and genetics of yeast. What a
chromosomes. Using improved techniques, as Maj Hultén
coincidence then that one of my children should be born
so charmingly recounts, these scientists had shown that
with a chromosomal defect! After the children were born,
we actually have 23 pairs. As an academic physiologist,
I worked part time as a freelance abstractor of current
my father thought the momentous genetic discoveries of Top: Dad
literature for a pharmacological/medical publishing
the 1950s would interest his three young children. (Professor John
company. Mills); middle:
He was right, but it wasn’t for another thirty years that Fabian, Prisca,
Since Jenny’s birth, I have devoted a great deal of my time Ann; bottom:
these facts were to take on a personal significance for my
and energy to promoting the needs of families with Sophie.
husband Nigel and myself, when our second son Toby was
disabled children. As one time Vice-Chair of Action for
born with a variety of medical problems. Sadly, Toby
Carers (Surrey) and a founder member of the East Surrey
never recovered from surgery the night after his birth to
Carer’s Support Association, I have had a lot of experience
repair his diaphragmatic hernia. Before he died, blood
working with Social Services and Health Authority
samples were sent for analysis and within weeks we
representatives. I also served for four years as a Non-
learned that the underlying cause of his multiple
Executive Director of a NHS Trust for People with
anomalies was a partial trisomy of chromosome 22.
Learning Disabilities.
Stepwise investigations then revealed that not only did I
Most enjoyably, though, I have been involved in the
carry an 11;22 balanced translocation but my brother
running of Unique. My husband Trevor is a computer
Fabian and my sister Ann had exactly the same
software specialist and together we have developed
chromosomal re-arrangement. As my mother had normal
Unique’s members’ database and the group’s website.
chromosomes, the conclusion that the translocation was
When I first had Jenny, I was very upset and really passed on by my father was inescapable. He was no
thought that was the end of any decent life for me. Well, longer alive to discover this but would, I think, have been
6 even now, it is difficult at times but I can honestly say that
in most ways, my life has changed immeasurably for the
intrigued and, given my parents’ apparently problem-free
reproductive history, mildly surprised.
7
Amniocentesis in my next pregnancy showed the same immeasurable. I would never have had that loving little boy
balanced 11;22 translocation, so since the birth of our who throws his arms around me and just wants the
daughter Sophie in 1983 it now spans three generations. reassurance of a hug and a kiss. I love him to bits!
Professionally, I have worked in medical journalism for In 1996 I became Information Officer for the group and
most of my life, starting out as editor of the then British then Administrative Officer in 1999. In June 2003 I became
Diabetic Association’s journal Balance, and later Family Support Officer, which covers all of my supportive
contributing to a range of medical and consumer roles. I send out all of the new members welcome packs, I
publications, as well as writing three child health coordinate our local contacts’ around the world and since
handbooks. 1996/7 I have organised Unique’s conferences and
meetings. As area representative for West Sussex, I try my
Working as Unique’s Information Officer offers a
best to help raise the profile of Unique in the Sussex area.
wonderful opportunity for the personal and professional
strands of my life to intertwine. It is very exciting indeed
to come on board for the launch of Unique’s innovative
I am proud to be a part of such a wonderful organisation.
❞
project to compile and publish information on the rare
and, in some cases, very rare chromosome disorders that Julie Griffin – Finance and
❞
affect each of us. Fundraising Executive Officer
Marion Mitchell
❝ Iside
work part time for Unique looking after the money
of things, pay out cheques, pay in receipts, control
regular giving, tax, insurance and statutory
– Family Support Officer requirements like annual accounts, etc. I also work with
❝ I(28.4.94)
joined the group in May 1995, just after my son Robert
was diagnosed with an inverted duplication of
Beverly in applying for new grants and looking at new
ways we can make the most of the funds that we have.
chromosome 15 (idic 15).
I work part time as a marketing manager with LTSB
Rob has severe learning difficulties and attends a specialist Business at their Head Office in Bristol. I have worked for
secondary school for children with learning difficulties the Bank since 1986 in a variety of roles and am enjoying
(mild, moderate, severe and profound). Rob has sensory the marketing role I do now, which I hope Unique benefits
dysfunction, and very poor fine motor skills. from too. Julie, Patrick and Nathan.
Steve, Marion and Robert. Rob is non-verbal and communicates using objects of I am married to Patrick and we had two children, Nathan
reference (cup for drink, etc.) He has mobility problems (28.2.97) and Georgina (19.11.01 - 5.12.03). Georgina
caused mainly by his hypotonia (floppiness), abnormal gait had an unbalanced translocation, with duplication on 4q
and subluxating hips. Rob also has epilepsy and eczema. and small deletion on 8p. She had severe learning
difficulties, was tube fed, and developed epilepsy at 5
We were given Rob’s diagnosis at the age of 1 and were
months old. She died just 2 weeks after her second
lucky enough to be given Unique’s details that day by our
birthday – following an operation for a gastrostomy and
local child development centre.
malrotation of the bowel, she unfortunately developed
I am married to Steve and Rob is our only child. Influenza A and Adenovirus and never regained
consciousness.
I am so glad I wasn’t put in the position of being offered an
amniocentesis (I was a year younger than the offering age), Working for Unique I have gained an enthusiasm to give
because I wasn’t given an opportunity to make the difficult back something to the group that supported me so well
decision that some families have to make, besides which, I during all those difficult times. I am also actively involved
was unable to have any more children (unrelated to Rob’s in fundraising events, especially ones which mean having
disorder which is de novo [new]). Although we have been a good time as well. Having Georgina changed our lives
8 through some difficult times – I can’t imagine life without
Rob, he is an absolute joy and the pleasure he gives us is
in so many ways, but I wouldn’t have had it any other
way as we are all richer as a tribute to her.
❞
9
Maj Hultén – Medical Advisor beautiful spreads of human chromosomes. This was the
first time human chromosomes could be correctly counted
❝ When I was little I lived in a small town in southern
Sweden. Every Sunday I saw marches of unusual looking
and proper photographs taken.
children walking hand in hand in the street outside our It is a truism to say that I can remember it as if it was
house. My mother told me that they lived all together, yesterday- the stinging smell of the chromosome stain
because their parents had found it difficult to look after (Acetic Orcein) blending together with that of Turkish
them. She also said that sometimes it could happen that coffee made by the visiting scientist, Joe Hin Tjio, who had
there was more than one child in a family with similar produced the chromosome preparations, squashing the cells
problems. between two pieces of glass – making his thumbs bright
red also. Sitting on a high laboratory stool I was
I was hooked and years later decided to study Psychology drumming my legs against the bench in excitement, while
and Education at the University of Stockholm to learn pointing out to Dr Tjio that it could now be possible to
more about what could cause such problems – and how find out if some people with learning disabilities may have
Maj Hultén. they could be overcome. I took my exams, but was chromosome abnormalities such as trisomies, monosomies,
disappointed not finding any real answers to my questions.
translocations, insertions, inversions, rings, duplications
Genetics I thought then might be a better bet. This also
and deletions, previously only seen in fruitflies and plants,
turned out to be frustrating, not least because formalities
as if he would not have realised this by himself.
at the time dictated that courses in Genetics were only
open to students who had spent several years studying I decided on the spot to study medicine, hoping that
Zoology and Botany – and who had also passed an Medical Genetics would one day become a discipline,
entrance exam. Luckily I managed to strike a deal with the where the study of chromosomes would be very important.
Professor to the effect that if against all odds, I would be This was now more than 40 years ago. I have worked with
ranking no 1 in the Genetics Entrance Exam, he would chromosomes and genetic counselling ever since. One of
accept me regardless. This was hard work, but it did work. the challenges I faced was to convince Edna Knight to take
me on board as Medical Advisor to the Rare Chromosome
I found the Genetics course fascinating, yet disappointing,
Disorder Support Group. I am glad she eventually did –
primarily because the curriculum mostly concerned
around 15 years ago.
bacteria, fruitflies and plants – and statistics, hardly
anything that could explain learning disabilities in I should add that my brother has had a child with a
children. Chromosome Disorder, a deletion of the long arm of
In my final year I had to do a special project, taking a chromosome 8. He and my sister-in-law have not had the
couple of months. I was offered a number of projects (17 in benefit of a Support Group. My vision is that Unique one
total) pushing around and counting different types of day will be renowned not only for the help the Group
fruitflies under a dissecting microscope. I declined them provides to families in the UK (and some other countries
all, and said I should like to look at human chromosomes. already) but also for the powerful stimulus it has meant
This turned out to be a decisive turning point. It was for the creation of similar Groups in many, many other
arranged for me to be supervised by a Professor Levan, countries. As far as I am aware Rare Chromosome
who had been looking at mouse chromosomes, particularly Disorders are equally common among all races and all
in tumours. (As it happened this was in the same small different parts of the world. So, in this respect we are not
town in southern Sweden, where I had grown up). Unique! I also nourish a dream that never again should a
doctor turn around to parents saying- ‘Your child has got a
I was given a project, studying the effects of radiation very rare Chromosome Disorder. I am afraid I know
treatment on mouse tumours… nothing about it!’ As I am sure many parents have, I have
But, lo and behold, I later found out that work on human found this very off putting. It should of course not have
chromosomes was actually going on in the same happened in the past, and let us hope the mission of
10 Department! The night before Christmas Eve in 1955 I
was offered to peer down the microscope to look at
Unique will imply this type of ignorance becomes
❞
increasingly rare in the future.
11
consequences of chromosomal rearrangement can still develop
differently. There are many other factors besides a
person’s chromosomal disorder that affect how they
rare chromosomal disorders develop, for example, the unique mixture of genes
on their other normal chromosomes, the
environment in which they are raised and so forth.
The effects of rare chromosomal disorders can be
Sometimes a particular chromosome disorder will
very varied. The vast majority of carriers of balanced
give a similar pattern of problems. If enough
rearrangements will have no symptoms but might
children are born with this similar pattern, then this
have problems in reproduction. Where there has
can be called a SYNDROME.
been a loss or gain of chromosomal material, the
symptoms arising might include a combination of There are also some general characteristics of rare
physical problems, health problems, learning chromosomal disorders that occur in the majority of
difficulties and/or challenging behaviour. The affected people to varying degrees. For instance,
combination and severity of effects occurring very most people with any loss or gain of material from
much depend upon which parts of which chromosomes 1 to 22 will have some degree of
chromosomes are involved. The outcome for the learning disability and developmental delay. This is
affected children can be quite different. In general, because there are many genes located across all these
loss of a segment of a chromosome is more serious chromosomes that code for normal development of
than the presence of an extra copy of the same the brain. Defects in any one of them could have a
segment. Defects of chromosomes 1 to 22 tend to be harmful effect on normal development.
far more serious than those of the sex chromosomes You might have been dismayed if the doctors and
X and Y. It is very important that a child’s geneticists that you have consulted about your
chromosomal disorder is specified in as much detail child’s chromosomal disorder are not able to give
as possible. The description of a person’s you a definite idea of how your child will be affected
chromosomal make-up is called their KARYOTYPE. in the long term, especially if the disorder is
Sometimes children with the same karyotype will particularly rare. You might think that the doctors
show similar problems. However, even children with simply do not want to help or can’t be bothered to
the same karyotype can differ in some or even nearly find out. Nothing could be further from the truth.
all of their problems. Why should this be? The The point is that, like any other child, your child is
karyotype only gives us the “big” picture as seen UNIQUE and while there might have been other
under a light microscope. If you were able to look at similar chromosomal disorders reported in the
a much greater magnification, the actual breakpoints medical literature, it does not mean to say that your
in the chromosome might be many genes apart. But child will develop in the same way. Like any of us,
even that does not explain all the differences. Even doctors do not have a crystal ball to look into the
12 brothers and sisters with the same karyotype

inherited as the result of a parent’s balanced
future. They might only be able to give you an idea
of the possible problems that might arise.
13
You, or your family and friends, might have asked
what can be done to “cure” a chromosomal disorder
in your baby or child. Nothing can be done about
what can unique do
the actual chromosomal defect because every single
one of the billions of affected cells would have to to help?
have missing chromosomal material added or extra
material taken away and this is just not possible. Having a child with a rare chromosome disorder can
However, symptoms caused by the chromosomal be a huge shock and can stir up a whole range of
disorder can be treated as they arise and the best emotions and a great desire to learn more about your
environment given in order for the child with the child’s disorder. All of us who help run the group
chromosomal disorder to reach their full potential. have been through these experiences and know how
you are feeling. Most parents’ first reaction, quite
understandably, is to “find” another, older child with
the same disorder as their child. Whilst this might
be possible for some, it still does not mean that the
two children will develop in the same way.
However, just talking to other parents with a child
with a rare chromosomal disorder can be a great
relief and can help to alleviate feelings of isolation
and “why me?”.
As part of its services, Unique runs a helpline

(+44 (0) 1883 330766) for new and existing families
and professionals to find out more information about
the group and about specific rare chromosomal
disorders. A comprehensive computerised database
has been developed detailing the effects of specific
rare chromosomal disorders amongst members. The
database can be used to link families on the basis of
specific rare chromosomal disorder. Often of more
practical benefit, however, is to link families on the
basis of problems as they arise, whether these are
medical, developmental, behavioural, social,
educational and so on. Unique also maintains close
links with other similar groups around the world,
thus increasing the “pool” of possible family
14 contacts. Information about a specific rare

chromosomal disorder can be prepared from the
15
Unique database whilst not revealing the identity of
the families concerned. Unique has also developed a
website (www.rarechromo.org) and can be contacted
all about
by email (info@rarechromo.org).
Many local groups and contacts have been formed
chromosomes and genes
throughout the UK (and even in a few other When parents discover that their child has a rare
countries). Families affected by any rare chromosomal disorder, they often find themselves
chromosomal disorder can come together locally for confronted with a very steep learning curve. Any
general support and friendship and to pass on information learnt about genetics in biology classes
information about services available in their at school may be a distant memory. Here we will try
neighbourhood. Unique publishes a regular to provide you with the basic facts about
newsletter in which families can write about their chromosomes and the different types of rare
experiences and exchange useful information. The chromosome disorders. If you find the information
group also holds a regular conference in various a bit complicated, please don’t be put off but do
venues across the UK where families and ask if you aren’t sure what anything means.
professionals can meet and discuss latest
developments. Unique can also act as a go-between
Cells, Chromosomes,
to enable families to participate in any research
projects relevant to their child’s condition.
DNA and Genes FIG. 1 Increasing
magnification to show
Whatever your specific needs, Unique will try to where chromosomes and
genes are found in the
provide you with tailor-made information and help human body.
relevant to your child’s disorder. Please make use of Cell Membrane
these services - Unique is YOUR group. Human Cells

grouped together
Cytoplasm
Nucleus
Chromosomes
Individual
Human cell
Genes strung along the

DNA of a Chromosome
A Chromosome
The human body is made up of billions of individual

CELLS. With the exception of the red blood cells,
each of these cells contains a structure called the
NUCLEUS, which is held within a thick fluid called
16 the CYTOPLASM. Inside the nucleus are found the

CHROMOSOMES, which contain the GENES. Genes
17
are “strung” along the chromosomes, a bit like beads of one copy of each autosomal chromosome but also
along a necklace. Genes are the instructions that tell either one copy of the X chromosome or one copy of
the body how to develop and work properly. the Y chromosome. So it is the father’s sperm that
determines whether a child will be a boy (XY) or a
Apart from the mother’s EGG cells or the father’s
girl (XX).
SPERM cells, every cell in the human body normally
contains 23 PAIRS of chromosomes, making 46 Under the microscope, chromosomes look like long, Telomere
chromosomes in total in each cell. This number of thread-like bodies. They have a SHORT ARM
chromosomes is known as the DIPLOID number. (labelled “p”, which stands for petit, the French Short Arm (p)
The Human Genome Project has shown there to be word for small) and a LONG ARM (labelled “q”).
about 30,000 genes in every cell. These genes are Linking the two arms is a narrower region called the
Centromere
spread unevenly across the chromosomes, some CENTROMERE. The ends of the chromosomes are
chromosomes having many more genes than other called the TELOMERES. The telomeres stop the
chromosomes and some parts of each chromosome chromosome from unravelling, a bit like the plastic
holding more genes than other parts. Of the 23 pairs tips of a shoe-lace. Long Arm (q)
of chromosomes in each of these cells, one member

Chromosomes are so named because they are able to
of each pair is normally inherited from the father Chromatids
take up certain dyes or stains. “Chromos” is the
and the other member is normally inherited from the FIG. 2 The structure of a
Greek word for coloured and “soma” is the Greek chromosome.
mother. Members of each pair of chromosomes are
word for “body”. Different stains give each
called HOMOLOGOUS chromosomes. The first 22
chromosome a particular pattern of light and dark
pairs of chromosomes are called the AUTOSOMES
bands. It is the location of the centromere and the
and are numbered from 1 to 22 according to their
specific banding pattern of a chromosome that
length, starting with number 1 as the longest. The
allows it to be identified.
chromosomes in the 23rd pair are called the SEX
CHROMOSOMES. Sex chromosomes are labelled X Chromosomes are built up of a chemical called DNA
or Y. Males normally have one copy of the X (DeoxyriboNucleic Acid) and some proteins. Genes
chromosome and one copy of the Y chromosome in are composed of small stretches of some of the DNA
each cell; it is the Y chromosome that determines in chromosomes.
“maleness”. Females, on the other hand, normally The DNA is held in a twisted shape called a DOUBLE
have two copies of the X chromosome but no Y
HELIX. This double helix is tightly coiled but these
chromosome.
coils are then coiled again and then yet again, a bit
The number of chromosomes in the egg or sperm is like if you twist a shoe-lace until it is coiled tightly
different from that in other body cells. The mother’s into a ball. If you uncoiled all the DNA in just one
eggs each contain only 23 chromosomes (the diploid cell until it was pulled out to its fullest
HAPLOID number), made up of one copy of each extent, it would measure around two metres! If all
FIG. 3 The DNA
autosomal chromosome (1 to 22) along with one the DNA from the billions of cells in a mature adult double helix.
18 copy of the X chromosome. The sperm from the

father also contain 23 chromosomes, again made up
human were stretched out end to end, it could be
wrapped around the Equator up to 5 million times!
19
DNA has two very important jobs. It works very fluid samples to see if a fetus is carrying an
much like an assembly line in a factory. It acts as the abnormality. The cell samples have first to be grown 36.3
36.2
TEMPLATE or blueprint for assembly of all the up under special laboratory conditions and this can 36.1
35
proteins in our bodies. When most people think of be very time-consuming, especially if amniocentesis 34.3
34.2
protein, they tend to think of it as an important part samples are to be analysed. This is one reason why it 34.1
33
of the food they eat or as a major component of the can take several weeks for the results of a 32.3
32.2
32.1
structure of their muscles. While some proteins are chromosome analysis to be reported. 31.3
31.2
p
indeed very important as part of the structure of our Cytogeneticists will use special chemicals to stop the
31.1
bodies, others have essential parts to play in cells they are examining at an appropriate stage 22.3
22.2
controlling how our bodies work properly. Some when the chromosomes are at their most compact.
22.1
proteins act as enzymes, which make the chemical At this stage, called METAPHASE, the chromosomes
21
reactions in our bodies happen more easily and can be stained with different dyes. The stain used
13.3
13.2
13.1
quickly, while others act as hormones, which help most often is called GIEMSA in a technique 12
11
11
control our body’s proper functioning and producing G-BANDED chromosomes. 12
development. Some proteins even help control the

Different stains give the chromosomes a 21.1
production of other proteins by different genes. The 21.2
21.3
characteristic pattern of light and dark bands which
process of protein production is a very complex one 22
helps with their identification. Sometimes the 23
and yet, most of the time, the correct proteins are 24

chromosomes are analysed when they are a little less
made to keep our bodies working properly and 25
compact so that more bands can be seen and smaller q

healthily. With rare chromosomal disorders, though, 31
extra or missing pieces of DNA can be identified.
many thousands of genes might be missing or extra
This is called High Resolution Analysis. Diagrams of 32.1
and so essential proteins are either not made at all or
chromosomes showing these banding patterns are 32.2
32.3
are made in too many copies or are made incorrectly
called IDEOGRAMS. Other newer analytical 41
or at the wrong time. The second important function 42.1

techniques have been developed which are used in 42.2
42.3
of DNA is to pass on the genetic blueprint from old 43
addition to these staining methods. These newer 44
cells to new cells and from parent to child. An
techniques include, for example, Fluorescent In-Situ
accurate copy of the DNA in each chromosome has Fig. 4 Ideogram of
Hybridisation (FISH). G-Banded Chromosome 1.
to be made every time a new cell is formed.
Fig. 5 FISH stained chromosomes.
Chromosome Analysis
Specialist scientists called cytogeneticists examine a
person’s chromosomes for defects. Usually, they will
analyse the chromosomes in the white cells
(lymphocytes) in a person’s blood. They can also
analyse the chromosomes found in the cells of other
20 body tissues like bone marrow or skin or they might

analyse the cells from chorionic villus or amniotic
21
As we have already mentioned, a person’s 46,XX,del(8)(p23.1pter)
chromosomal make-up is called their KARYOTYPE.
This karyotype tells us that this person has 46
Obviously, it would be impractical always to have to chromosomes in each of their cells. The person has
show a photograph of someone’s chromosomes in two X chromosomes and so is a female. The “del”
order to describe precisely any chromosomal stands for deletion and so the female has a deletion of
part of chromosome 8. The chromosome has broken in
disorder they might have. As a consequence,
the short arm (“p”) at region 2, band 3, sub-band 1
cytogeneticists have devised a standardised code to and the rest of the short arm up to the terminus or end
describe a person’s karyotype. This system is called (pter) is missing. So band 8p23.1 is the BREAKPOINT
the International System for Human Cytogenetic in this deletion.
Nomenclature (ISCN). The most recent version was
47,XY,+9/46,XY
published in 1995. This means that anyone
understanding the code will have a precise This describes a male (X and Y chromosomes present)
with 47 chromosomes in one cell line, the extra
Fig. 6 Normal Female Karyotype. description of a person’s chromosomal disorder.
chromosome being a complete copy of chromosome 9,
In general, the ISCN code is written so that the with a second cell line with a normal chromosomal
make-up. This is what we would call Trisomy 9 Mosaic.
number of chromosomes in a person’s cells comes
first, followed by their sex chromosome make-up
46,XX,r(22)
and then by a description of any chromosomal
This describes a female with 46 chromosomes, one
disorder. Using this method, a normal male
copy of chromosome 22 being a ring chromosome.
karyotype would be described as 46,XY and a There is no indication given of the breakpoints.
Fig. 7 Normal Male Karyotype. normal female karyotype as 46,XX.
Any breakpoints in chromosomes are described by a 46,XY,t(2;5)(p22;p15.1)
standardised numbering system based on the This describes a male with 46 chromosomes and a
balanced reciprocal translocation between
banding patterns produced in G-banded
chromosomes 2 and 5 with breakpoints at bands 2p22
chromosomes. The bands allow the chromosomes to and 5p15.1. The segments 2p22 to 2pter and 5p15.1 to
be mapped into REGIONS, which in turn are divided 5pter have swapped places with each other but no
into BANDS and then into SUB-BANDS. This is a bit chromosomal material has been lost or gained.
like being able to identify a house along a road if
you know the house number. With the ISCN 46,XY,der(5)t(2;5)(p22;p15.1) mat
numbering system, the higher the number of the This describes a male with 46 chromosomes and an
unbalanced translocation involving chromosomes 2 and
breakpoint, the further away from the centromere it
5. One chromosome 5 is a derivative (der)
can be found. To help you understand this system chromosome with loss of part of the short arm from
more clearly, take a look at some examples of band 5p15.1 to 5pter. An extra piece of chromosome 2
karyotype descriptions. from 2p22 to 2pter has been attached to the derivative
chromosome at 5p15.1. This means that the person
with this unbalanced translocation has a deletion of
part of chromosome 5 combined with a duplication of
part of chromosome 2. The translocation has arisen as
22 a result of a balanced translocation in the mother (mat). 23
You might already have been given your own child’s minus sign (-) Loss
karyotype and would like to work out exactly what
mos Mosaic
the code means. If you do not know your child’s
karyotype, ask your doctor or geneticist so that you p Short arm of chromosome
too have a proper description of your child’s parentheses ( () ) Surround structurally altered
chromosomal disorder. Here is a list (Table 1) of the chromosomes and breakpoints
more common symbols used in karyotype pat Paternal origin

descriptions. plus sign (+) Gain
psu Pseudo
Symbols used in Karyotypes q Long arm of chromosome
Symbol Description question mark (?) Questionable identification of a
add Additional material of unknown chromosome or chromosome
origin structure
arrow (->) From - to r Ring chromosome
cen Centromere rcp Reciprocal
single colon (:) Chromosomal break rec Recombinant chromosome
double colon (::) Chromosomal break and reunion rob Robertsonian translocation
comma (,) Separates chromosome numbers, semicolon (;) Separates altered chromosomes
sex chromosomes and and breakpoints in structural
chromosome abnormalities rearrangements involving more
than one chromosome
decimal point (.) Denotes sub-bands
slant line (/) Separates cell lines (used in
del Deletion mosaic karyotypes)
de novo Designates a chromosomal t Translocation
abnormality which has not been
inherited tel Telomere
der Derivative chromosome ter Terminal (end of chromosome)
dic Dicentric trp triplication
dup Duplication
i Isochromosome
idic Isodicentric chromosome
ins Insertion
inv Inversion
mar Marker chromosome (extra
chromosome of unknown origin)
24 mat Maternal origin 25
rare chromosomal When individual whole chromosomes are
missing or extra, this is called ANEUPLOIDY.
This can happen with any of the autosomal
disorders chromosomes (1 to 22) or the sex

chromosomes (X and Y).
Some changes or mutations in chromosomes are so If one extra complete chromosome is present,
small they only affect a single gene and these are this is known as TRISOMY and the number of Fig.9 Karyotype showing a single extra
known as single gene disorders. However, when chromosomes in each affected cell would be 47. chromosome (T21).
changes in chromosomes are large enough to be seen Probably the most well-known example of Trisomy
using a light microscope, they are called is Down Syndrome (Trisomy 21).
chromosome aberrations or disorders. Visible Two extra complete chromosomes would be called
disorders usually involve many genes and can be TETRASOMY and the number of chromosomes
classified into two main types, NUMERICAL would be 48. If a complete chromosome is missing,
DISORDERS and STRUCTURAL DISORDERS. If this is known as MONOSOMY and the number of
these disorders arise during the formation of the egg chromosomes in each cell would be 45.
or the sperm cells, then the disorder would be
passed on to every cell in the body of a child STRUCTURAL DISORDERS
produced. If the disorder arises in one of the new
cells produced soon after the egg has been fertilised Structural disorders occur because of breakages in a
by the sperm, then only a proportion of the child’s chromosome. They can occur spontaneously (this is
cells will be affected and this is called MOSAICISM called DE NOVO) or they can be inherited from a
parent. Structural disorders include various types of
translocation, deletions, ring chromosomes,
NUMERICAL DISORDERS duplications, inversions and isochromosomes.
If cells carry complete
extra sets of Translocations
chromosomes, this is
known as POLYPLOIDY. A translocation happens when DNA is transferred
When there is one extra from one non-homologous chromosome to another.
set, to give 69 They include reciprocal translocations, Robertsonian
chromosomes in total, translocations and insertional translocations.
this is called TRIPLOIDY. Translocations can be balanced or unbalanced.
If only some of the body’s

Fig. 8 Ideogram and Triploid Karyotype.
Balanced Reciprocal Translocations
cells carry the extra set of chromosomes, then this is
known as Triploid Mosaicism, or Diploid Triploid
and Unbalanced Translocations
Mosaicism or even Mixoploidy. Balanced reciprocal translocations as a whole are
26 thought to occur at a rate of about 1 in 500 in the 27
general population. Balanced reciprocal chromosome number of 45. Robertsonian
translocations happen when breaks occur in two or translocations are relatively common in the general
more different chromosomes and the resulting population (about 1 in 1000), the most frequent
fragments of DNA swap places. No chromosomal being fusion of the long arms of chromosomes 13
material has been lost or gained and so the vast and 14. The significance of a Robertsonian
majority of carriers of a balanced reciprocal Translocation is the risk of miscarriage or of
translocation do not have any symptoms. There can producing children with an unbalanced chromosome
➤
be rare exceptions to this. Symptoms can occur make-up.

occasionally when children are born with de novo
balanced reciprocal translocations, especially when Insertions
more than two different chromosomes are involved.
Insertions occur when a segment of one
This is thought to be due, at least in part, to
chromosome is inserted into a gap in
disruption of important genes at the chromosome
another chromosome. If someone carries
breakpoints. However, if the child carries the same
a balanced insertional rearrangement,
balanced reciprocal translocation as their
they should not have any symptoms
FIG. 10 Ideogram showing a
symptomless parent, then they should also not
balanced reciprocal translocation (unless a critical gene is disrupted at the
(above) and two possible experience symptoms caused by the translocation.
unbalanced translocations that can breakpoints) but they are at risk of
arise in the offspring (below). The problems with balanced reciprocal FIG 11 The Knight family with
producing a child with either a deletion ideograms of their chromosomes 9 and
translocations arise because carriers are at risk of or a duplication of chromosomal 20. Edna (left) has a balanced insertion
of part of chromosome 9 in
producing offspring with part of one chromosome material but not both disorders. chromosome 20, as has daughter Claire
missing and part of another extra. Such (not shown). Julie and Wendy (centre)
have partial duplications of the short
translocations are unbalanced and may lead to arm of chromosome 9, while Linda
Deletions (right) has normal chromosomes.
miscarriage or the birth of children with symptoms
including learning difficulties and physical A DELETION involves loss of a part (a segment) of a
disabilities. Balanced reciprocal translocations tend chromosome and is sometimes known as a PARTIAL ➤ p22
MONOSOMY. Deletions can occur in any part of any p
to be unique to individual families and so it is very
important that families consult a genetic counsellor chromosome. If the segment is lost from near to the
so that the specific risks of miscarriage and bearing centromere, this is called a PROXIMAL DELETION.
children with disabilities can be discussed. If the segment is lost from nearer to the end of the
chromosome (the telomere), then the deletion is q
called a DISTAL DELETION. If there is just one
Robertsonian Translocations
break in the chromosome, then the deletion is called
Robertsonian translocations occur when the short a TERMINAL DELETION. (Terminal just refers to
➤ denotes breakpoints arm of certain chromosomes (chromosomes 13, 14, the end of the chromosome and does not infer that FIG 12 Ideogram showing a partial
15, 21 or 22) are lost and the remaining long arms the deletion will be lethal to the child.) If there are deletion of the short arm of
chromosome 9 (right) along with
fuse together. Loss of the short arms of these two breaks in the arm of the chromosome with the its normal homologous
28 chromosomes should not cause any symptoms. A

person with a Robertsonian translocation has a total
intervening segment being lost and the remaining
chromosome (left).
➤ denotes breakpoint 29
parts of the chromosome joining up, then this is breaks occur in the same arm of the chromosome,
called an INTERSTITIAL DELETION. Some this is called a PARACENTRIC INVERSION. If one ➤
p
deletions are particularly small and are called break occurs in the short arm and the other in the
MICRODELETIONS. long arm of the chromosome, then this is called a
PERICENTRIC INVERSION. Usually, inversions do
Rings not cause problems in the carrier (unless important
genes are disrupted) but there is a risk of producing q
➤
A RING chromosome usually forms when the ends
sperm or eggs with unbalanced chromosomes.
of both arms of the same chromosome are deleted.
Carriers of paracentric inversions very rarely give ➤
➤
The remaining broken ends of the chromosome are
birth to children with abnormalities. On the other A B C D
“sticky” and join together to make a ring shape.
➤
hand, carriers of pericentric inversions more FIG 15 Ideogram of a pericentric

Usually, it is the missing DNA that is significant. In inversion of chromosome 10 (B)
frequently give birth to children with abnormalities.
effect, the person with a ring chromosome has a with its normal homologous
These children will have a partial duplication of one chromosome (A) and of a
terminal deletion of both the short and the long paracentric inversion of
arm of the affected chromosome along with a partial chromosome 16 (D) and its normal
arms of the chromosome. However, if the ring homologous chromosome (C).
deletion of the end of the other arm of that
chromosome is present as an extra (or The inverted segments lie between
chromosome or vice versa. The closer the the black arrows.
FIG 13 Ring Chromosome. SUPERNUMERARY) chromosome, then it is the
breakpoints are to the ends (telomeres) of the
chromosomal material that has NOT been deleted
chromosomes, the greater the chance of the child
that is significant. The material in the extra ring
surviving to birth. This is because the chromosome
chromosome has effectively been duplicated. Some
segments deleted and duplicated will be smaller.
geneticists believe that there can also be a general
effect caused by any ring chromosome, poor growth
and developmental delay being the outcome.
Isochromosomes and ESACs
p
Sometimes people carry an extra or supernumerary
Duplications chromosome made up of parts of one or more q13 ➤
p
chromosomes. They will effectively carry a
A DUPLICATION occurs when an extra copy of a
duplication or triplication of the material forming q
segment of a chromosome is present. A duplication
this extra chromosome. If the origin of the extra
is sometimes known as a PARTIAL TRISOMY. If a
chromosome is unknown, it is sometimes referred to
q person has two extra copies of a chromosomal
as an extra structurally abnormal chromosome
segment, then this is known as a TRIPLICATION or
➤
(ESAC) or a marker chromosome. If the extra
a PARTIAL TETRASOMY. FIG. 16 Ideogram of Isodicentric
chromosome is made up of two copies of the same (idic) 15 (right) with two copies of
segment of a chromosome, this is called an part of a chromosome and two
➤ Inversions isochromosome. When these extra chromosomes
normal chromosomes 15 (left).
➤ denotes breakpoint
FIG 14 Ideogram showing partial carry two copies of the same centromere, they are
duplication of the long arm of
Inversions occur when there are two breaks in a
chromosome 1 (right) along with single chromosome. The segment between the called isodicentric chromosomes.
its normal homologous
breakpoints turns through 180 degrees and reinserts
30 chromosome (left).
➤ denotes breakpoint itself into the “gap” left in the chromosome. If both 31
further reading and donations, fundraising
information and gift aid
If you would like to read more detailed books about We are very grateful to the National Lottery
medical genetics (aimed at the medical or Charities Board for funding the Development Officer
cytogenetics student or qualified doctor), find out Post from April 1999 to March 2002 and for the
what those incomprehensible medical and production of this booklet. However, most other
cytogenetic terms mean or keep up to date with services offered by Unique are paid for by voluntary
papers published about specific rare chromosomal donations, fundraising and Gift Aid. To help us to
disorders, the following may be helpful. keep our services free to members, please give
generously if you can.
“Essential Medical Genetics”, 5th Edition, by Michael
Connor & Malcolm Ferguson-Smith, Blackwell You can donate by sending a cheque, made payable
Science, ISBN 0-86542-666-X to Unique, in GB pounds, Euros, US dollars or
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by Robert F. Mueller & Ian D. Young, Churchill
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website. Please send any donations to:
“ISCN 1995: An International System for Human
Julie Griffin
Cytogenetic Nomenclature”, Ed. Felix Mitelman, S.
Unique Finance and Fundraising Executive Officer
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179 Bakers Ground
“Dorland’s Illustrated Medical Dictionary”, Edition 28, Stoke Gifford
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The Online Mendelian Inheritance in Man (OMIM) Telephone: +44 (0) 117 979 8886
website www.ncbi.nlm.nih.gov/Omim Facsimile: +44 (0) 117 979 8886
Email: donations@rarechromo.org
The Medline website www.ncbi.nlm.nih.gov/PubMed
(lists abstracts of papers published about medical For more information about donating or fundraising
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Little Yellow Book About The Facts On Rare Chromosome Disorders

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The

Unique would like to acknowledge the Sporting Bears Motor Club

Vol 1: A Guide to Rare Chromosome Disorders

Rare Chromosome Disorder Support Group

rare chromosomal disorders..............................................................26 The group is run predominantly on a voluntary

12 brothers and sisters with the same karyotype

As part of its services, Unique runs a helpline

14 contacts. Information about a specific rare

these services - Unique is YOUR group. Human Cells

Genes strung along the

The human body is made up of billions of individual

16 the CYTOPLASM. Inside the nucleus are found the

of chromosomes in each of these cells, one member

18 copy of the X chromosome. The sperm from the

development. Some proteins even help control the

helps with their identification. Sometimes the 23

and yet, most of the time, the correct proteins are 24

compact so that more bands can be seen and smaller q

or at the wrong time. The second important function 42.1

20 body tissues like bone marrow or skin or they might

more common symbols used in karyotype pat Paternal origin

arrow (->) From - to r Ring chromosome

cen Centromere rcp Reciprocal

single colon (:) Chromosomal break rec Recombinant chromosome

der Derivative chromosome ter Terminal (end of chromosome)

dic Dicentric trp triplication

disorders chromosomes (1 to 22) or the sex

If only some of the body’s

be rare exceptions to this. Symptoms can occur make-up.

28 chromosomes should not cause any symptoms. A

hand, carriers of pericentric inversions more FIG 15 Ideogram of a pericentric

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