Medical Genetics

出生缺陷出生缺陷

Birth DefectsBirth Defects

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Birth defects are defined as abnormalities of structure, function, or body metabolism that are present at birth.

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1. General1. General

One of the most common worries for expectant parents is that something will be wrong with their baby.

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Understanding the nature and causes of birth defects can help reduce the mystery, fear and guilt often associated with them.

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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.

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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.

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Some defects are often not discovered until later (eg deafness and problems in walking).

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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.

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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.

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2. Forms of Birth Defects2. Forms of Birth Defects

Defects of limbs, heart and spinal cord represent about half of all abnormalities.

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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.

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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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si ngl e gene di sordersmi t di seasePol ygene di sorderschromosomal di seaseunkonwn

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•Chromosome disorder

•Mitochondrial disease

Single gene disorder •Ploygene disorder

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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).

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3.The cause of birth defects 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.

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A. Genetics Genetics play a role in birth

defects. One missing or faulty gene can cause a birth defect.

• gene mutation• Chromosome aberration

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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.

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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.

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• Treatment ： for pregnancy reaction• untoward effects ： defect of limbs(phocomelia)

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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.

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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.

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Some anticonvulsant medicines used for epilepsy may also cause problems ： hare lip, limbs defects, congenital heart disease

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Moderate alcohol use in pregnancy is a particularly tricky problem.

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Smoking is bad for the development of the baby in a number of ways. Pregnant women should not smoke under any circumstances.

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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

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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.

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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

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herpes simplex4weeks 61%5-8weeks 26%9-10weeks 6%Heart defects deafness cataract

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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).

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Toxoplasma • Toxoplasma is a species of parasite • The definitive host of the cat, but the

parasite can be carried by many warm-blooded 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.

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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!).

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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.

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4. When a baby most vulnerable4. 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.

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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.

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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.

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'sensitive period

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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 five-week 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 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.

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caused by the incomplete closure of the embryonic neural tube.

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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.

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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 endcoccyx end

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spina bifida occulta

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• 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.

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• meningocelemeningocele

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•

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Spinous process Central canal Skin partially covering the neural tube defectSpinal cordDura mater

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• 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.

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• 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)

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1 Spinous process 2 Spinal cord 3 Dura mater 4 Skin up to the neural tube defect

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• 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

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