birth defects developmental biology ppt

congenital disorders are also known as congenital abnormalities, congenital malformations or birth defects. they can be defined as structural or functional anomalies that occur during intrauterine life and can be identified prenatally ,at birth, or sometimes may only be detected later in infancy , such as hearing defects.

1. BIRTH DEFECTS Mona khimsuriya                             roll no. - 16

2. What are birth defects ? Birth defects are structural or functional abnormalities present at birth that can cause physical or mental disabilities or both. They can occur during pregnancy and may affect various parts of the body . Birth defects can range from mild and treatable conditions to severe and life-  threatening ones.

3. Causes of birth defects  The causes of birth defects are genetic and environmental factors have been implicated in selected defects. These include prenatal environmental factors , such as infections ( e.g., rubella) ,exposures to medications or other chemicals ,drug or alcohol abuse or nutritional deficiencies.

4. Genetic factors Abnormalities caused by genetic events ( gene mutations, chromosomal aneuploidies and translocations ) are called malformations and a syndrome is a condition in which two or more malformations are expressed together. Pleiotropy – the production of several effects by a single gene or pair of genes.

5. Mosaic and relational pleiotropy (A) in mosaic pleiotropy , a gene is independently expressed in several tissues. Each tissue needs the gene product and develops abnormally in its absence.   (B) in relational pleiotropy , a gene product is needed by only one particular tissue. However a second tissue needs a signal from the first tissue in order to develop properly. If the first tissue develops abnormally ,the signal is not given , so the second tissue also develops abnormally.

6. Mitochondrial inheritance The body receives all its mitochondrial DNA only from the mother ,because during fertilization mitochondria of sperm do not pass into the ovum . Consequently disease which occur due to mutations in the mitochondrial DNA are inherited entirely through mother. 

7. The leading example of disease caused due to mutations in the mt DNA are : Leber's hereditary optic neuropathy (LHON) : A condition characterized by sudden onset of blindness in adults. Pearson marrow –pancreas syndrome (PMPS) : a condition characterized by a loss of bone marrow cells during childhood. It is frequently fatal.

8. Environmental factors Abnormalities caused by environmental agents are called disruptions. The environmental factors may be either biological ( e.g. viruses and parasites) or non biological such as physical factors (e.g. temperature ,radiation) and chemical factors ( e.g. drug , chemicals and nutritional imbalances ). The exogenous agents responsible for the disruptions are called teratogens.

9. Natural teratogens  Chemicals Certain chemicals naturally occurring in some plants can be highly teratogenic. Skunk cabbage ( veratrum californicium ) growing in the pristine alpine meadows of the rocky mountains can cause severe abnormalities in the fetus of sheep or cattle feeding on this plant. Birth defects include neurological damage and cyclopia . Two chemicals produced by this plant  jervine and cyclopamine inhibit cholesterol synthesis in the developing fetus and prevent sonic hedgehog from functioning, thereby causing severe brain defects including the lack of pituitary gland. Another plant product quinine can also cause congenital malformation such as deafness.

10. 2. ionizing radiation Excessive amount of radiation are teratogenic. They cause chromosomal fragmentation, alter DNA structure leading to mutations . Exposure of the fetus to radiation also caused impaired cell division , cell death and malignancy. A small dose of radiation will most likely kill  pre-implantation embryos.

11. Pharmaceutical teratogens (therapeutic drugs as teratogens) 1. Thalidomide The transqulizer thalidomide is one of the most famous and notorious teratogens. The most noticeable feature of fetuses exposed to this drug was  phocomelia  , a condition in which the long bones of limbs are either greatly reduced in length or absent. Even a single tablet could cause severe damage to the developing limbs. Other abnormalities in the affected children include malformed intestine ,hearing defects , absence of external ears and renal anomalies. 

12. 2. retinoic acid Retinoic acid or vitamin A derivatives are extremely teratogenic in humans. Even at very low doses oral medications such as isotretinoin used in the treatment of acne are potent teratogens. The critical period of exposure appears to be from the second to the fifth week of gestation . The most common malformations include craniofacial dysmorphisms, cleft palate , thymic aplasia and neural tube defects.

13. Industrial teratogens Industrial teratogens include lead ,mercury , arsenic, zinc and cadmium. The critical period of exposure to lead is 12- 14 weeks of gestation in humans . F etal exposure of lead is through maternal ingestion of food and beverages containing the metal . L ead is not easily  excreted and it continues to accumulate in fetal brain causing neurological defects. Methyl mercury is extremely toxic to humans . It accumulates in the fetal tissues through placenta . High levels of mercury results in altered neuronal migration and binds directly to DNA and RNA altering their conformation.

14. Microbial teratogens Rubella Abnormal babies are born to women suffering from rubella ( German measles) during the first five weeks of pregnancy . The abnormalities include microphthalmia, cataracts, glucoma , cardiac malformations, hearing loss and mental retardation.  2. cytomegalovirus (CMV) & herpes simplex Cytomegalovirus  infection early in gestation is fatal while infection of later embryos might lead to blindness  , deafness, cerebral palsy and mental  retardation . 3 . toxoplasma Toxoplasma goondii  is a protozoan parasite carried by rabbits and cats. It can cross the placenta causing hydrocephaly , microphthalmia , chorioretinitis , brain lesions and multiple organ damage and dysfunction in the fetus.

15. 4. syphilis Treponema pallidium is the cause of syphilis. Several hundred children are born each year with syphilis. Early infection most often results in spontaneous abortion. New borns which survive are anemic having spleen and liver malformations. They also have skin lesions, nasal discharge, bone and joint pains.

16. Recreational teratogens Alcohol Children of alcoholic mothers suffer from many birth defects referred to as fetal alcohol syndrome ( FAS). Alcohol permeates the placenta and enters fetal circulatory system causing developmental abnormalities. Infants born to alcoholic mothers demonstrate prenatal and postnatal growth deficiency, mental retardation and other malformations. There are subtle but classical facial features associated with fetal alcohol syndrome including short palpebral fissures , maxillary hypoplasia , a smooth philtrum and congenital heart disease.

17. 2. tobacco and cocaine  Women who smoke during pregnancy are 80% more likely to have spontaneous abortions as compared to a non smoker. Maternally inhaled nicotine can be detected in fetal lung. Nicotine restricts placental blood flow to fetus resulting in chronic hypoxia and malnutrition leading to birth defects. There is also reduction in overall fetal length , reduced head size and certain facial anomalies like cleft lip and palate.

18. Cocaine which is an anesthetic and vasoconstrictor also induces birth defects by disrupting placental vasculature thereby inducing hypoxia and malnutrition .  Fetuses exposed to cocaine show  retarded growth , microcephaly, urinogenital anomalies and neuronal and behavioral  abnormalities    There is also risk of premature labour , spontaneous abortion and fetal death.

19. REFERENCE DEVELOPMENTAL BIOLOGY SCOTT F. GILBERT http://www.columbia.edu/itc/hs/medical/humandev/2004/chpt23-teratogens VISHRAM SINGH GENERAL ANATOMY WITH SYSTEMATIC ANATOMY RADIOLOGICAL ANATOMY MEDICAL GENETICS , SECOND EDITION