Osteogenesis
Imperfecta (OI)
in
(ðáôÞóôå åäþ ãéá åðéóôñïöÞ óôçí åëëçíéêÞ ãëþóóá)
**You
can download the whole website,
in word format, (in English): here.**
The following text is mainly based
on www.oife.org
*** WHAT IS OI ***
Osteogenesis Imperfecta (OI) is a rare heritable disorder of
the connective tissue.
Literally OI means imperfect bone formation. This refers to the most prominent
feature of OI: bone fragility. Without a clear immediate cause the bones of an
affected person may fracture. This can happen at any age, even before birth.
There are various synonyms for OI in most languages:
In the English Literature OI has been discussed under
the following 34 eponyms
·
Osteogenesis
Imperfecta
·
Adair-Dighton disease (syndrome)
·
Aplasia periostalis
·
Blegvad Haxthausen syndrome
·
Blue sclera syndrome
·
Blue sclerotics and brittle bones
·
Blue scleras and fragilitas ossium
·
Brittle bones and blue sclerae
·
Dark sclerotics and fragilitas ossium
· Dysplasie périostale
· Dystrophie périostale
· Eddowes disease (syndrome)
· Ekman syndrome
· Ekman-Lobstein syndrome
·
Fetal rickets
·
Fragile bones
·
Fragilitas vitrea ossium
·
Hereditary fibrous osteodysplasia
·
Hereditary hypoplasia of the mesenchyme
·
Lobstein's disease
·
Molities ossium
·
Osseous fragility
·
Osteogenesis Imperfecta congenita (Vrolik)
·
Osteogenesis Imperfecta tarda
·
Osteomyopathia
·
Osteoporosis foetalis
·
Osteopsathyrosis ideopathica (Lobstein)
·
Osteopsathyrosis foetalis
·
Osteitis parenchymatosa chronica
·
Rachitis congenita
·
Spurway-Eddowes syndrome
§
§ Vrolik disease (syndrome)
· Van der Hoeve -
De Kleyn syndrome
People with OI have brittle bones!
Symptoms of OI
Fragility
differs widely from person to person, so the number of fractures can vary from a
few to over a hundred. All connective tissue is involved, not only that in
bone. Besides bone fractures this may cause a variety of symptoms like:
It must
be stressed that:
an
affected person may show some but usually does not show all these symptoms.
Many people
are only very lightly affected and show hardly any symptoms at all.
OI expresses
itself very individually, it is variable between persons and unpredictable per person.
Classification
In 1979 Sillence proposed a
classification of OI in 4 types based on the clinical features. With some minor
alterations this classification is still used. It is not always possible to
determine the OI type for every individual:
It has been established that in type(s) I the
defect causes a reduced production of normal collagen, sometimes resulting in a
low bone mineral density (BMD); while in the other types structurally abnormal
collagen (sometimes also in a lower amount) is produced, resulting in low
quality bone usually with a low BMD. Until now, any further clear
correspondence between the clinical types as defined above and the genetical
defects causing OI has not been found. Also, the importance of the typing
should not be overestimated. In daily life the severity of the condition could
be far more important. In the old days OI was classified as OI congenita or OI
tarda, meaning that the OI manifested itself before birth or sometime
thereafter. These terms have become obsolete.
WARNING:
This classification should not be used for "self diagnosis", always
seek the advice of a medical specialist familiar with OI.
*** INHERITANCE ***
O.I. is
a genetic disease and, as such, is inheritable. The types I and IV sometime
appear in families, through various generations. The mode of inheritance of the
disease is dominant: an affected parent has a 50% chance of transmitting
his/her altered gene to the offspring, and a 50% chance of transmitting the
normal counterpart (we all carry two copies of any given gene, with the exception
of genes linked to the sex chromosomes).
Although
a certain degree of variability (e.g. the number of fractures) is observed
within affected relatives, the clinical type in a given family generally
remains the same through generations, since the same basic genetic defect is
passed from parent to child. OI on the other hand, is highly heterogeneous in
unrelated cases: each individual case may represent a different genetic defect
in the collagen genes. OI, as other dominant genetic disorders, can appear also
spontaneously. This statement is particularly true for the types III and type
II (usually more severe forms of OI), but is also applicable to the other
types. When a child with O.I. is born from unaffected parents, we assume that a
mutation has occurred in a collagen gene. Mutations are sporadic, unpredictable
events which change the DNA informational content. Most likely the mutation
occurred in either gamete (ovocite or sperm cell) the merging of which gave
origin to the affected baby. In families where a spontaneous OI case occurs,
the unaffected siblings do not carry the mutation so they do not have
particular genetic risks for their progeny; the affected child, on the
contrary, has a 50% risk of transmitting the mutant gene and therefore the
disease, to his/her children, starting a new chain of hereditary OI through
generations.
In conclution: OI is dominantly
inheritable, which means that when one of the parents has OI then for each
newborn child the chance to be affected is 50%. In many cases OI is not
inherited but is caused by a mutation. In these cases none of the parents shows
any sign of OI. The mutation is again dominantly inheritable. The issue is
further complicated by the possibility of mosaicism. Because of the
complexity of the matter it is recommended to seek personal genetic advice.
*** MOSAICISM***
As for the
parents, studies on a wide number of families where unaffected parents had a
type II (lethal) OI baby, have shown recurrence of the disease (i.e. another
pregnancy with OI) in 5-7% of the cases. This puzzling situation at first was
explained erroneously with a different mode of inheritance (autosomal
recessive) and can still generate confusion (and wrong genetic advice) with
clinicians who are not updated in the OI field. Peter Byers and collaborators
(at the University of Seattle- USA) and, subsequently, many other
investigators, have demonstrated that the recurrence of OI in families with
negative clinical history is due to dominant mutations in either collagen gene
(COL1A1 or COL1A2): the causal mutation, instead of involving a single germ
cell, is carried only by a certain proportion of the germ cells of a given
parent (either mother or father), who therefore runs the risk of generating
more than one affected child. This
phenomenon is called mosaicism. It is very difficult to recognize mosaic individuals:
searching for the mutation in them would be just like to look for a needle in a
haystack. Only after the mutation has been identified in the affected child
(who carries it in all his/her cells), it is possible to design specific
molecular assays to test the parents for the presence of mosaicism (generally
detectable in both germ cells and white blood cells) and to try to estimate
their hypothetical recurrence risk. Mosaicism can occur for any clinical OI
form, but so far it has been documented extensively only for the severest form
(type II): its frequency has been estimated empirically to range between 5-7%.
Diagnosis
OI can
be quite difficult to diagnose. Many doctors are not familiar with it, and many
cases go undetected. It is a myth that all people with OI have blue sclerae. Only a certain percentage of
people with OI have blue sclerae. Occasionally child abuse is suspected
when the child in fact has OI, this is a particularly frustrating experience
for the family involved. If you think that you or your child may have OI ask
your national OI society to direct you to a specialist who is familiar with OI.
Cause of OI
In most cases OI is caused by
a defect in either of the two genes
that code for collagen I, i.e.
COL1A1 on chromosome 17 or
COL1A2 on chromosome 7. The defect disturbs the production of collagen. In OI
type I too little, but normal, collagen is produced. In the other types the
collagen is of bad structural quality, while the amount of collagen may be
reduced as well.
Treatment
It is not expected that the
cause of OI can be eliminated in the near future. Therefore OI can not be cured
at the moment. However, careful treatment can alleviate the circumstances.
Treatments are aimed at reducing the impact of the consequences and at the
prevention of complications. Often this calls for an integral management plan,
which may encompass: orthopedic treatment of fractures, hearing
improvement, dental intervention, physiotherapy, psychological
assistance, genetic counselling and DNA testing, social advisory, ergotherapy
with advice on crutches and wheelchairs and other equipment, sometimes also
dietary advice. Attention should be given to the prevention of osteoporosis,
as people with OI are more vulnerable to this than other people. Recently
several types of bisphosphonates have been used as drugs with apparently
good results, but it is still too early to draw conclusions.
*see also: Bisphosphonates Treatment in Children under 2 Years of Age (*.pdf 284KB)
Prognosis
Because
of the individual variability of OI it is impossible to make general statements
about the prospects of an affected person. It is recommended to seek personal
advice. In many cases fragility diminishes after puberty for reasons still
unknown.
Incidence
OI is a rare disorder. Its
incidence is estimated at 1:10.000 to 15.000. This estimate is a lower limit
because light forms of the disease are quite often not recognised. OI occurs in
all races and is independent of gender. Only 0.008% of the world population is
affected by OI. This means that at present there are about 0.5 Million persons
with OI in the world. Details on the OIFE members can be found on the statistics page.
Life & OI
In spite of the restrictions
that OI may impose People with OI can lead a happy life as a valued member of
society. Many people with OI live independently and pursue careers (some are
even famous). They can be married or living in stable relationships and have
children. Mutual support by exchange of experience and information is of prime
importance for people with OI and their families. Please contact your
national OI society for further information and help.
Theofilos Koupidis
ÌD Biopathologist
In spite of the combined efforts of medical
professionals and patient/parent organizations on OI over the past decades it
still happens that the impact of the first information given by the diagnosing
doctor to the parents of a newborn child with OI is gravely underestimated. The
OI societies are regularly confronted with cases in which parents of an OI
child have been given the diagnosis and the first information from a doctor who
has little or no knowledge of OI and a lack of sensitivity. Frequently the
doctor of first contact mainly describes some possible negative physical
symptoms of this rare genetic disorder which would make their child's life
miserable and probably cause early death. Usually this doctor was not aware of
more knowledgeable colleagues or the existence of an OI society. If parents are
suddenly confronted not only with the diagnosis of OI but as well with a
prognosis for deficiencies and disabilities, numerous fractures, hearing loss
etc. without any offer of hope and concrete helpful information and without any
hint as to the more positive aspects it is not difficult to imagine that the
impact of such information can be disastrous. It is known that some parents
completely lose hope and give up their child immediately (leave it in
hospital), because they see no way how to cope with such circumstances. In the
opinion of the OIFE this kind of misinformation and its consequences should and
could be avoided. The medical professionals need to be aware of the importance
of adequate initial information to the parents of their little patients, they should direct parents to specialists and OI
societies who are available to offer information and personal support. We call
upon you as the medical professionals to discuss with us how we can raise more
awareness on this issue and how we can combine our efforts to spread this
request and all other relevant information on OI. Further down you will find an
example of how adequate, balanced information to new parents could look like.
Copied from www.oife.org
Copied from www.oife.org
Fast facts on OI
What
is Osteogenesis Imperfecta?
Osteogenesis
Imperfecta (OI) is the medical name for brittle bones. `Brittle Bones' refers
to a range of conditions resulting from abnormalities in the protein structure
of the bones. This causes the bones to break more easily than normal.
What
is it like to have brittle bones?
Some
children with OI are born with fractures, others have
their first injury soon after birth, yet others when they try to walk for the
first time. This is obviously a difficult time for the family and a large part
of the society's work is to provide the guidance, support and information that
they need. In a few cases children with brittle bones are, initially thought to
have been injured by their parents. This accusation does great damage to the
families and the Society can provide advice and support.
Does
it vary in severity?
There
are several types of OI and people with the condition may experience only 10 -
20 fractures during their childhood years, others may have 100 or more
fractures. All parents have a difficult task stopping their children taking
risks but also trying not to be over protective. In fact most people with
osteogenesis imperfecta, given the support they need, can lead active and
fulfilled lives.
Is
it an inherited disorder?
In
some cases, mostly milder ones, the disorder passes from one generation to
another. In most severe cases it comes `out of the blue' with no signs in either
parent.
What
can be done to help?
Quite
a lot can be done to make life better for those with OI. There is no `cure' but
work is progressing into a number of possible drug treatments, however these
are still at the stage of clinical trials and are not widely available. Each
fracture has to be treated carefully to ensure the bones heal properly and
Orthopaedic surgery can be of help in many cases.
Is
any special equipment necessary?
Most
children with OI can enjoy a high standard of mobility, though some will
require the use of very specialised wheelchairs that
may not be available through local statutory services. Equipment such as
specially adapted keyboards, or other input devices linked to a computer can be
of great benefit where people with OI are unable to make full use of their
fingers.
Do
the children go to ordinary schools?
Most
children with OI can be educated in mainstream primary and usually secondary
schools. Good education is important because these children are bright and
given the right opportunities can lead independent lives.
What
is medical research achieving?
Research
has shown that brittle bones is not one condition but a group of several
hundred all caused by abnormalities in the structure of the protein component
of bone known as `collagen'. These abnormalities are caused by defects in the
genes that tell the cells how to make collagen. Osteogenesis imperfecta is not
caused by a lack of calcium.
Advances in our understanding of these disorders has
enabled us to ensure that families get accurate genetic advice. In the future
these advances may lead to more effective treatments for brittle bones.
Copied from http://www.brittlebone.org
(child with OI in
My name
is Koupidis Theofilos and I am a medical doctor specialized in laboratory
medicine (Biopathologist). I have a son (born on August 16, 2003), who has at
least 7 fractures since his birth (one on his left humerus in Sept2003, one on
his right femur in Dec2003 , and four in his left
femur from Mars 2004 until July 2005). He has not blue
sclera, he has not major deformities.
Birth:
3,85 kilos and
6months: 7,1 kilos and
8months: 7.5 kilos &
10
months:
26
months:
At the
age of 8 months, I examined his blood and I found that :
Ht= 35.3 %, Hb=11.4, RBC=4.81x106,
PLT= 350.000, ÌCV=73.4, MCH=23.7, MCHC=32.3, RDW=16.8,
WBC= 14.450, (G=8%, L=75%, M=12%, E=1%, others=4%) SGOT=40, SGPT=16, GLU= 92, UREA= 15, KRE= 0.33, Ca= 10.9, K= 5.4,
P=7.0, Na=142, ALP=206, PTH (intact)=21.5 pg/ml, Vit D=35.7 pg/ml, Zn=90ìg/dl, Cu=139ìg/dl.
From Rx-check on
his cranium the findings are: ‘.. many
bormian (wormy) bones….’.
After all that, he
took periodically Pamidronate
(i.v.) in ‘Paidon Agia
Sofia, Athens’ (the first session was in May 2004).
Since April 2005 , he takes pamidronate iv every 3 months in
hospital of Veria (near our home).
His mobility is fine, he
doesn’t walk intepentently yet, but we hope for
the best.
We had an operation in
December 2005 (F-D Rodding in both femurs).
Our ortho ,
Dr Kanellopoulos (who works in ‘’KAT hospital’’) told us that it went
well.
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FOR THE LATEST NEWS ABOUT
CHRISTOS KOUPIDIS CLICK HERE :
http://users.ima.sch.gr/lenaarva/latest_news_en.html
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OI Foundation (OI Society of the USA)
webpage of a pioneer
doctor on OI in USA
http://www.shef.ac.uk/medicine/staff/bishop/index.php
webpage about
a pioneer doctor on OI in GB
http://ceciliaykerstiens.tripod.com/babyjonathan/id16.html
Jonathan
story (child with ÏÉ)
http://groups.msn.com/thetsurifamily/february.msnw
photo of Alexi
(child with ÏÉ)
‘Ag. Sofia children hospital’ in Athens
http://www.oocities.org/oi_gr/paper_babies.pdf (*.pdf 284KB)
Bisphosphonates Treatment in Children under 2 Years of Age