Medical Genetics
17 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
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
Understanding the nature and
causes of birth defects can help
reduce the mystery,fear and guilt
often associated with them,
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,
Medical Genetics
The third most common kind of
defect affects the spinal cord,such
as spina bifida,
Medical Genetics
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,
Medical Genetics
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
A,Genetics
Genetics play a role in some
birth defects,One missing or faulty
gene can cause a birth defect,
Medical Genetics
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
However,most defects that can
be traced to a single cause have a
genetic origin,This does not
necessarily mean that the parents
suffer from the same defect,
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,
Medical Genetics
There are three main kinds of
factor that can cause defects,
chemical,biological and physical,
Medical Genetics
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
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
antibiotics affect hard tissue formation
during the foetal period,affecting the long
bones and teeth,Some anticonvulsant
medicines used for epilepsy may also
cause problems,Anyone on long-term
medication who is planning to become
pregnant,or who has become pregnant,
should discuss their situation with their
doctor,
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,
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
Other viruses,such as
cytomegalovirus and herpes simplex,can
also cause problems,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
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 child-
bearing 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
For instance,some babies may have a genetic
susceptibility to certain environmental factors,If
exposed to such factors during development,
they may develop an abnormality,If they are not
exposed to the factor,they will be perfectly
normal,Another baby exposed to the same
environmental factor,but who doesn't have the
genetic susceptibility,may be entirely normal,
This can make it difficult to pin down the exact
cause of a defect,
Medical Genetics
The Human Genome Project has
worked out the normal sequence of
all genes found in people,In the
future,this will be invaluable in
teasing out the relative roles of
genetics and the environment in
causing birth defects,
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
Conversely,if babies are exposed
to different damaging factors at the
same stage in development,the
damage caused may well be similar,
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 to,
say,radiation at three weeks may
cause similar damage to rubella,
Medical Genetics
Medical Genetics
The developing baby is
particularly vulnerable to
environmental factors during a five-
week period starting about three
weeks after fertilisation,and lasting
till about the end of the eighth week
after fertilisation,
Medical Genetics
Pregnancy is usually timed from
the last menstrual period,which is
generally about a fortnight before
fertilisation,'Three weeks after
fertilisation' therefore corresponds to
the 'fifth week of pregnancy' and
'eight weeks after fertilisation' to the
'10th week of pregnancy',
Medical Genetics
This five-week interval is often called
the 'sensitive period' as it is crucial to
normal development,Even within this
period,the body organs form at different
times,Sometimes it is possible to
estimate retrospectively from the nature
of the defect when the baby might have
been exposed to a possible environmental
factor,The mother's medical history can
then be examined to see what she was
exposed to over this period,
Medical Genetics
5,How detected in advance
Diagnosis of birth defects has
been revolutionised by the
widespread use of ultrasound,
Ultrasound scanning seems to be
very safe in normal use,
Medical Genetics
Blood tests for expectant mothers
are also valuable,The 'triple test' is
widely used,In this,levels of alpha-
fetoprotein,human chorionic
gonadotrophin and oestriol in the
mother's blood are measured,
Various abnormalities are associated
with alterations in their levels,
Medical Genetics
A common further test is
amniocentesis,when a sample of the
fluid surrounding the baby is
removed,and the cells in the fluid
are checked,This procedure poses a
small risk of inducing a termination
of pregnancy,
Medical Genetics
6,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
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,
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 to control seizures may
have an increased risk of having a baby
with spina bifida,
Medical Genetics
There are two forms of spina
bifida — spina bifida occulta and
spina bifida manifesta,
Medical Genetics
Medical Genetics
Medical Genetics
Medical Genetics
Medical Genetics
7,Congenital heart defects
A congenital heart defect is a
structural problem (or defect) in the
heart that is present at birth,A
baby's heart begins to develop
shortly after conception,During
development,structural defects can
occur,
Medical Genetics
These defects can involve the
walls of the heart,the valves of the
heart,and the arteries and veins
near the heart,Congenital heart
defects can disrupt the normal flow
of blood through the heart,
Medical Genetics
Multiple genetic and
environmental factors interact to
alter the development of the heart
during the early stages of a fetus'
development (the first 8 to 9 weeks
during pregnancy),
Medical Genetics
Types of Congenital Heart Defects
There are many types of congenital
heart defects,They include,
1,Abnormal passages in the heart or between
blood vessels
2,Problems with the heart valves
3,Problems with the placement or development of
blood vessels near the heart
4,Problems with development of the heart itself
Medical Genetics
A,Abnormal passages in the heart
or between blood vessels
? Atrial septal defect (ASD)
? Ventricular septal defect (VSD)
? Atrioventricular septal defect (AVSD)
? Patent ductus arteriosus (PDA)
Medical Genetics
Atrial septal defect (ASD) is
a hole in the wall that separates the
upper chambers (atria (AY-tree-uh))
of the heart,This causes blood to
leak from one atrium to the other,
Medical Genetics
Medical Genetics
Ventricular septal defect
(VSD) is a hole in the wall that
separates the lower chambers
(ventricles (VEN-trih-kuls)) of the
heart,This causes blood to leak from
one ventricle to the other,
Medical Genetics
Medical Genetics
Patent ductus arteriosus (PDA) is
a persistent connection between the aorta
and the pulmonary (PULL-mun-ary) artery,
This connection is called the ductus
arteriosus and is normally present before
birth,In most babies,the vessel closes
within a few hours or days after birth,In
some children,the vessel fails to close,
resulting in PDA,
Medical Genetics
Medical Genetics
B,Problems with the heart valves
Congenital heart defects can
involve any of the valves and include
the following types of problems,
? Stenosis,
? Atresia,
? Regurgitation,
Medical Genetics
C,Problems with placement or
development of blood vessels
near the heart
? Transposition of the great vessels
? Tetralogy of Fallot
? Truncus arteriosus
? Coarctation of the aorta
? Anomalous pulmonary venous return
Medical Genetics
Tetralogy of Fallot is a combination of four
defects,
? Pulmonary valve stenosis is the narrowing of the
pulmonary valve,The narrowing slows the flow of
blood from the right ventricle to the lungs,
? VSD is a hole in the wall that separates the left
and right ventricles,
? Overriding aorta is a defect in which the aorta is
positioned between the left and right ventricles,
over the VSD,
? Right ventricular hypertrophy is the thickening of
the right ventricle,The thickening is caused by
the heart having to work harder because of the
other defects,
Medical Genetics
D,Problems with development of the heart
? Hypoplastic left heart syndrome is a combination
of defects in which the left side of the heart does
not develop properly,Defects usually include
mitral atresia,aortic atresia,and a tiny left
ventricle,
? Single ventricle describes a group of heart
defects in which only one ventricle is present
instead of two,It can be a single right or a single
left ventricle,The other ventricle is usually
absent or very tiny,Hypoplastic left heart
syndrome is an example of a single ventricle
defect,
17 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
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
Understanding the nature and
causes of birth defects can help
reduce the mystery,fear and guilt
often associated with them,
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,
Medical Genetics
The third most common kind of
defect affects the spinal cord,such
as spina bifida,
Medical Genetics
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,
Medical Genetics
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
A,Genetics
Genetics play a role in some
birth defects,One missing or faulty
gene can cause a birth defect,
Medical Genetics
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
However,most defects that can
be traced to a single cause have a
genetic origin,This does not
necessarily mean that the parents
suffer from the same defect,
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,
Medical Genetics
There are three main kinds of
factor that can cause defects,
chemical,biological and physical,
Medical Genetics
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
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
antibiotics affect hard tissue formation
during the foetal period,affecting the long
bones and teeth,Some anticonvulsant
medicines used for epilepsy may also
cause problems,Anyone on long-term
medication who is planning to become
pregnant,or who has become pregnant,
should discuss their situation with their
doctor,
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,
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
Other viruses,such as
cytomegalovirus and herpes simplex,can
also cause problems,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
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 child-
bearing 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
For instance,some babies may have a genetic
susceptibility to certain environmental factors,If
exposed to such factors during development,
they may develop an abnormality,If they are not
exposed to the factor,they will be perfectly
normal,Another baby exposed to the same
environmental factor,but who doesn't have the
genetic susceptibility,may be entirely normal,
This can make it difficult to pin down the exact
cause of a defect,
Medical Genetics
The Human Genome Project has
worked out the normal sequence of
all genes found in people,In the
future,this will be invaluable in
teasing out the relative roles of
genetics and the environment in
causing birth defects,
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
Conversely,if babies are exposed
to different damaging factors at the
same stage in development,the
damage caused may well be similar,
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 to,
say,radiation at three weeks may
cause similar damage to rubella,
Medical Genetics
Medical Genetics
The developing baby is
particularly vulnerable to
environmental factors during a five-
week period starting about three
weeks after fertilisation,and lasting
till about the end of the eighth week
after fertilisation,
Medical Genetics
Pregnancy is usually timed from
the last menstrual period,which is
generally about a fortnight before
fertilisation,'Three weeks after
fertilisation' therefore corresponds to
the 'fifth week of pregnancy' and
'eight weeks after fertilisation' to the
'10th week of pregnancy',
Medical Genetics
This five-week interval is often called
the 'sensitive period' as it is crucial to
normal development,Even within this
period,the body organs form at different
times,Sometimes it is possible to
estimate retrospectively from the nature
of the defect when the baby might have
been exposed to a possible environmental
factor,The mother's medical history can
then be examined to see what she was
exposed to over this period,
Medical Genetics
5,How detected in advance
Diagnosis of birth defects has
been revolutionised by the
widespread use of ultrasound,
Ultrasound scanning seems to be
very safe in normal use,
Medical Genetics
Blood tests for expectant mothers
are also valuable,The 'triple test' is
widely used,In this,levels of alpha-
fetoprotein,human chorionic
gonadotrophin and oestriol in the
mother's blood are measured,
Various abnormalities are associated
with alterations in their levels,
Medical Genetics
A common further test is
amniocentesis,when a sample of the
fluid surrounding the baby is
removed,and the cells in the fluid
are checked,This procedure poses a
small risk of inducing a termination
of pregnancy,
Medical Genetics
6,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
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,
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 to control seizures may
have an increased risk of having a baby
with spina bifida,
Medical Genetics
There are two forms of spina
bifida — spina bifida occulta and
spina bifida manifesta,
Medical Genetics
Medical Genetics
Medical Genetics
Medical Genetics
Medical Genetics
7,Congenital heart defects
A congenital heart defect is a
structural problem (or defect) in the
heart that is present at birth,A
baby's heart begins to develop
shortly after conception,During
development,structural defects can
occur,
Medical Genetics
These defects can involve the
walls of the heart,the valves of the
heart,and the arteries and veins
near the heart,Congenital heart
defects can disrupt the normal flow
of blood through the heart,
Medical Genetics
Multiple genetic and
environmental factors interact to
alter the development of the heart
during the early stages of a fetus'
development (the first 8 to 9 weeks
during pregnancy),
Medical Genetics
Types of Congenital Heart Defects
There are many types of congenital
heart defects,They include,
1,Abnormal passages in the heart or between
blood vessels
2,Problems with the heart valves
3,Problems with the placement or development of
blood vessels near the heart
4,Problems with development of the heart itself
Medical Genetics
A,Abnormal passages in the heart
or between blood vessels
? Atrial septal defect (ASD)
? Ventricular septal defect (VSD)
? Atrioventricular septal defect (AVSD)
? Patent ductus arteriosus (PDA)
Medical Genetics
Atrial septal defect (ASD) is
a hole in the wall that separates the
upper chambers (atria (AY-tree-uh))
of the heart,This causes blood to
leak from one atrium to the other,
Medical Genetics
Medical Genetics
Ventricular septal defect
(VSD) is a hole in the wall that
separates the lower chambers
(ventricles (VEN-trih-kuls)) of the
heart,This causes blood to leak from
one ventricle to the other,
Medical Genetics
Medical Genetics
Patent ductus arteriosus (PDA) is
a persistent connection between the aorta
and the pulmonary (PULL-mun-ary) artery,
This connection is called the ductus
arteriosus and is normally present before
birth,In most babies,the vessel closes
within a few hours or days after birth,In
some children,the vessel fails to close,
resulting in PDA,
Medical Genetics
Medical Genetics
B,Problems with the heart valves
Congenital heart defects can
involve any of the valves and include
the following types of problems,
? Stenosis,
? Atresia,
? Regurgitation,
Medical Genetics
C,Problems with placement or
development of blood vessels
near the heart
? Transposition of the great vessels
? Tetralogy of Fallot
? Truncus arteriosus
? Coarctation of the aorta
? Anomalous pulmonary venous return
Medical Genetics
Tetralogy of Fallot is a combination of four
defects,
? Pulmonary valve stenosis is the narrowing of the
pulmonary valve,The narrowing slows the flow of
blood from the right ventricle to the lungs,
? VSD is a hole in the wall that separates the left
and right ventricles,
? Overriding aorta is a defect in which the aorta is
positioned between the left and right ventricles,
over the VSD,
? Right ventricular hypertrophy is the thickening of
the right ventricle,The thickening is caused by
the heart having to work harder because of the
other defects,
Medical Genetics
D,Problems with development of the heart
? Hypoplastic left heart syndrome is a combination
of defects in which the left side of the heart does
not develop properly,Defects usually include
mitral atresia,aortic atresia,and a tiny left
ventricle,
? Single ventricle describes a group of heart
defects in which only one ventricle is present
instead of two,It can be a single right or a single
left ventricle,The other ventricle is usually
absent or very tiny,Hypoplastic left heart
syndrome is an example of a single ventricle
defect,
