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Medical Genetics
出生缺陷
Birth Defects
Medical Genetics
Birth defects are defined as
abnormalities of structure, function,
or body metabolism that are present
at birth.
Medical Genetics
1. General
One of the most common
worries for expectant parents is that
something will be wrong with their
baby.
Medical Genetics
Understanding the nature and
causes of birth defects can help
reduce the mystery, fear and guilt
often associated with them.
Medical Genetics
However, most babies are born
without problems, while most of
those who are can have treatment
that will make them much better, or
even allow them to lead a normal life.
Medical Genetics
An international monitoring
programme shows that, across
Europe, just over 2 per cent of
babies are discovered at birth to
have a defect that will affect their
ability to survive or function normally.
Medical Genetics
Some defects are often not
discovered until later (eg deafness
and problems in walking).
Medical Genetics
There is considerable regional
variation in the rate of defects seen
at birth. Glasgow and Dublin have
traditionally been black spots, with
rates over 3 per cent, but these
figures are falling.
Medical Genetics
The number of babies actually
born with defects is also markedly
affected by the availability of
prenatal screening, and the
availability of voluntary termination
of pregnancy in the case of severe
abnormalities.
Medical Genetics
2. Forms of Birth Defects
Defects of limbs, heart and spinal
cord represent about half of all
abnormalities.
Medical Genetics
The most common
kinds of defect are those
affecting the limbs (arms
and legs). These include
missing or extra fingers or
toes, deficiencies in limb
length, and abnormalities
in positioning, such as club
foot.
Medical Genetics
Heart abnormalities
represent the next most
common category of defect.
Common heart defects
include 'holes in the heart'
where blood can pass from one
side of the heart to the other.
Again, these may not all be
detected at birth.
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The third most common kind of
defect affects the spinal cord, such
as spina bifida.
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Other defects commonly
observed include those
affecting the face (such as
cleft lip and palate), problems
with the development of the
intestines and stomach, and
problems affecting the sexual
organs.
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single gene disorders
mit disease
Polygene disorders
chromosomal disease
unkonwn
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Single gene disorder
•Ploygene disorder
•Chromosome disorder
•Mitochondrial disease
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Major chromosomal problems
such as Down's syndrome (Trisomy
21) are found in about 0.15 per cent
of births (about three babies in every
2000).
Medical Genetics
3.The cause of birth defects
In ancient times, abnormalities were
seen as warnings or punishments from
the gods. Even quite recently, it was
believed that specific events during the
pregnancy - such as being frightened by
a mouse - would lead to specific defects
in the baby, eg a mouse shaped birth
mark. Such folk beliefs still persist in
places.
Medical Genetics
A. Genetics
Genetics play a role in birth
defects. One missing or faulty gene
can cause a birth defect.
• gene mutation
• Chromosome aberration
Medical Genetics
It may be that they are carriers of
the condition, or that the genetic
problem occurred for the first time in
the cells that gave rise to the baby.
Known genetic causes account for
about 25 per cent of all abnormalities.
Medical Genetics
B. Environment
Environmental causes (including
exposure to drugs, radiation and illnesses)
can be identified in about 10 per cent of
birth defects. The risk of exposure to such
environmental factors often causes great
concern, although genetic causes are
more common.
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There are three main kinds of
factor that can cause defects:
chemical, biological and physical.
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Chemical factors, including drugs
Thalidomide is perhaps the most
notorious example of a drug that
caused defects. It was brought on to
the market after inadequate testing
and specifically prescribed for
pregnant women.
Medical Genetics
• Treatment： for pregnancy reaction
• untoward effects：defect of limbs(
phocomelia)
Medical Genetics
Medical Genetics
Following this, much stricter
rules about drug testing were
introduced, and international
monitoring programmes were put in
place. Doctors are also much more
cautious about prescribing drugs to
women of child-bearing age, so it is
unlikely that a disaster on this scale
will occur again in the UK.
Medical Genetics
Several medical treatments pose
the risk of birth abnormalities.
Tetracycline(antibiotic) ： affect hard
tissue formation during the foetal
period, affecting the long bones and
teeth.
Medical Genetics
Some anticonvulsant medicines
used for epilepsy may also cause
problems：hare lip, limbs defects,
congenital heart disease
Medical Genetics
Moderate alcohol use in pregnancy
is a particularly tricky problem.
Medical Genetics
Smoking is bad for the
development of the baby in a
number of ways. Pregnant women
should not smoke under any
circumstances.
Medical Genetics
Lack of something may be as
damaging as the presence of
something. Extensive trials have
confirmed that taking folic acid
before pregnancy can reduce the
number of spinal cord defects such
as spina bifida.
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• poisons & pollution
Cri du chat syndrome
Medical Genetics
Biological factors, including illnesses
The rubella virus, which causes German
measles, poses a serious hazard to the
developing baby. It can cross the
placenta and attack the baby to cause a
range of defects.
The proportion of mothers infected
with the rubella virus during the first 12
weeks of pregnancy who have an
abnormal child can reach 20 per cent.
Medical Genetics
cytomegalovirus also cause problems as
• Enlarged spleen
• Liver problems
• Jaundice (yellowing of the skin and eyes)
• Small size
• mental retardation,
• cerebral palsy
• vision and hearing loss
Medical Genetics
herpes simplex
4weeks 61%
5-8weeks 26%
9-10weeks 6%
Heart defects deafness cataract
Medical Genetics
Bacteria such as salmonella,
present in undercooked meat
(especially chicken), and listeria
(found in some cheeses), can cause
problems for the continuation of the
pregnancy (rather than birth defects).
Medical Genetics
Toxoplasma
• Toxoplasma is a species of parasite
• The definitive host of the cat, but the
parasite can be carried by many warmblooded animals .
• Toxoplasmosis, the disease of which T.
gondii is the causative agent, is usually
minor and self-limiting but can have
serious or even fatal effects on a fetus
whose mother first contracts the disease
during pregnancy.
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• Acute stage Toxoplasma often give flu-like
symptoms in the early acute stages
• The acute stage fades in a few days to
months, leading to the latent stage. Latent
infection is normally asymptomatic; but
some induce encephalitis, which can be
deadly
• If infection occurs for time during
pregnancy, the parasite can cross the
placenta, possibly leading to
hydrocephalus or chorioretinitis.
Medical Genetics
Physical factors (including radiation)
X-rays and radiation given as cancer
therapy can affect the baby. Your medical
carers will be very cautious about giving
you an abdominal X-ray if you are
pregnant or potentially pregnant (this
means almost every woman of childbearing age!).
Medical Genetics
C. Other factors
The exact causes of the
remaining 65 per cent of defects are
currently unclear. Many of these
defects arise from an interplay of
genetic and environmental factors.
Medical Genetics
4. When a baby most vulnerable
The time at which the developing
baby is exposed to a possibly
damaging environmental factor is
more important in determining the
nature of the likely abnormality than
the nature of the factor itself.
Medical Genetics
In fact, if babies are exposed to
the same damaging factor at
different times in their development,
the nature of the damage is likely to
be different.
Medical Genetics
For instance, exposure to the
rubella virus at three weeks after
fertilisation may cause heart defects,
and at six weeks after fertilisation, it
may cause deafness. Exposure
radiation at three weeks may cause
similar damage to rubella.
Medical Genetics
'sensitive period
Medical Genetics
Pregnancy is usually timed from
the last menstrual period, which is
generally about a fortnight before
fertilisation. Three weeks after
fertilisation to the '10th week of
pregnancy'.
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The developing baby is
particularly vulnerable to
environmental factors during a fiveweek period starting about three
weeks after fertilisation, and lasting
till about the end of the eighth week
after fertilisation.
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5. Spina Bifida
Spina bifida is a birth defect that
involves the incomplete development
of the spinal cord or its coverings.
The term spina bifida comes from
Latin and literally means "split" or
"open" spine.
Medical Genetics
caused by the incomplete closure
of the embryonic neural tube.
Medical Genetics
A. Types of Spina Bifida
The causes of spina bifida are largely
unknown. Some evidence suggests that
genes may be involved. A high fever
during pregnancy may increase a woman's
chances of having a baby with spina bifida.
Women with epilepsy who have taken the
drug valproic acid may have an increased
risk of having a baby with spina bifida.
Medical Genetics
Spina bifida occurs at the end of the
first month of pregnancy when the two
sides of the embryo's spine fail to join
together, leaving an open area. In some
cases, the spinal cord or other membranes
may push through this opening in the
embryo's back. The condition can typically
be detected before a baby is born and
treated right away.
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neural tube
Head end
coccyx end
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spina bifida occulta
Medical Genetics
• The vertebrae are not completely
closed. The skin at the site of the
lesion may be normal, or it may have
some hair growing from it.
• Many people with the mildest form of
this type of spina bifida do not even
know
• Back pain.
Medical Genetics
• meningocele
Medical Genetics
•
1
2
3
4
5
Spinous process
Central canal
Skin partially covering the
neural tube defect
Spinal cord
Dura mater
Medical Genetics
• the meninges are forced into the
gaps between the vertebrae.
• As the nervous system remains
undamaged, individuals with
meningocele are unlikely to suffer
long-term health problems, although
there are reports of tethered cord.
Medical Genetics
• The protruded portion of the spinal cord
and the nerves which originate at that
level of the cord are damaged or not
properly developed. As a result, there is
usually some degree of paralysis and
loss of sensation below the level of the
spinal cord defect. Thus, the higher the
level of the defect the more severe the
associated nerve dysfunction and resultant
paralysis
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myeloschisis (rachischisis)
Medical Genetics
1 Spinous process
2 Spinal cord
3 Dura mater
4 Skin up to the neural tube defect
Medical Genetics
• occurs when the spinal canal and
backbone do not close before birth,
causing the spinal cord to protrude
through an opening in the back. This can
cause partial or complete paralysis below
the spinal opening.
• Patients have loss of function of lower
extremities and may also have bowel and
bladder dysfunction.
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• Arnold-Chiari malformation
the medulla oblongata
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anencephalus
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• occurs when the cephalic (head) end of
the neural tube fails to close
• resulting in the absence of a major portion
of the brain, skull, and scalp.
• Children with this disorder are born
without a forebrain, the largest part of the
brain consisting mainly of the cerebral
hemispheres
• The remaining brain tissue is often
exposed—not covered by bone or skin
Medical Genetics