CONGENITAL ANOMALIESCONGENITAL ANOMALIES(Birth defects)(Birth defects)

A congenital anomaly is a structural A congenital anomaly is a structural abnormality of any type that is present at abnormality of any type that is present at birth.birth.

Congenital anomalies may be induced by Congenital anomalies may be induced by geneticgenetic or or environmental factorsenvironmental factors. Most . Most common congenital anomalies, however, common congenital anomalies, however, show the family patterns expected of show the family patterns expected of multifactorial inheritancemultifactorial inheritance (determined by a (determined by a combination of genetic and environmental combination of genetic and environmental factors).factors).

About About 3%3% of all liveborn infants have an of all liveborn infants have an obvious major anomaly. obvious major anomaly.

The incidence is about The incidence is about 6%6% in 2-year-olds in 2-year-olds and and 8%8% in 5-year-olds. in 5-year-olds.

Congenital anomalies may be Congenital anomalies may be single or single or multiplemultiple and of and of minor or majorminor or major clinical clinical significance. significance.

During the first During the first 2 weeks of development2 weeks of development, , teratogenic agents usually teratogenic agents usually killkill the the embryo or have embryo or have no effectno effect. .

During the During the organogenesis periodorganogenesis period (3rd (3rd –– 8th weeks), teratogenic agents disrupt 8th weeks), teratogenic agents disrupt development and may cause development and may cause major major congenital anomalies. congenital anomalies.

During the During the fetal periodfetal period (9th week (9th week –– 9th 9th month) teratogens may produce month) teratogens may produce morphological and functional morphological and functional abnormalitiesabnormalities, particularly of the brain , particularly of the brain and eyes. and eyes.

Causes of congenital anomalies

1-Genetic factors such as chromosomal abnormalities and mutant genes.

2-Environmental factors e.g.: the mother had German measles in early pregnancy will cause abnormality in the embryo.

3-Combined genetic and environmental factors (mutlifactorials factors).

Types of abnormalities1-Malformations: this occurs during the formation of

the structures of the organ (during organogenesis) results in partial or complete non formation or alterations in the normal structure. This occurs in the 3rd to the 8th week of gestation. Ex. Cleft lip and or cleft palate.

2-Disruptions: results in morphological change of the already formed structure due to exposure to destructive process. e.g.: vascular accidents leading to intestinal atresia, amniotic band disruption.

3-Deformations: due to mechanical forces that affect a part of the fetus over a long period. Ex: talipes equinovarus deformity.

4-Syndrome: is a group of anomalies occurring together due to a common cause .

The genetic factors leading to congenital The genetic factors leading to congenital anomalies may be due to chromosomal anomalies may be due to chromosomal abnormalities, gene mutations or may be abnormalities, gene mutations or may be multifactorial.multifactorial.

Chromosomal abnormalitiesChromosomal abnormalities occur due to: occur due to: - - late maternal agelate maternal age at the time of at the time of

pregnancy pregnancy (leads to chromosomal non-disjunction), (leads to chromosomal non-disjunction),

- - radiationradiation (causes chromosome deletions, (causes chromosome deletions, translocations or breaks), translocations or breaks),

- - virusesviruses as German measles, as German measles, - - autoimmune diseasesautoimmune diseases, , - and some - and some chemical agentschemical agents as anti-mitotic as anti-mitotic

drugs. drugs.

- - Chromosomal abnormalities are Chromosomal abnormalities are classified into numerical and structural.classified into numerical and structural.

Numerical chromosomal Numerical chromosomal anomaliesanomalies are divided into: are divided into:

1- 1- polyploidypolyploidy as as triploidytriploidy ( a fetus ( a fetus with 69 chromosomes) and with 69 chromosomes) and tetraploidytetraploidy where the fetus has 92 where the fetus has 92 chromosomes. Polyploidy leads to chromosomes. Polyploidy leads to severe congenital anomalies and severe congenital anomalies and early abortion.early abortion.

2- 2- AneuploidyAneuploidy (one or more chromosomes is added (one or more chromosomes is added or missed) as in: or missed) as in:

Down syndrome (trisomy 21),Down syndrome (trisomy 21),

Edward syndrome (trisomy 18), Edward syndrome (trisomy 18), Patau syndrome (trisomy 13), Patau syndrome (trisomy 13),

Turner syndromeTurner syndrome ((45,X or a female missing one ((45,X or a female missing one X), and X), and Klinefelter syndromeKlinefelter syndrome (47,XXY or a male (47,XXY or a male

person with an extra X chromosome).person with an extra X chromosome).

Structural chromosomal Structural chromosomal anomaliesanomalies include chromosomal include chromosomal deletion, duplication, translocation, deletion, duplication, translocation, inversion, and ring and iso inversion, and ring and iso chromosomes. It may also lead to chromosomes. It may also lead to severe congenital anomalies or fetal severe congenital anomalies or fetal death.death.

Environmental factors

1) Infectious Agents:1) Infectious Agents:1-Infectious agents include a number of viruses: Rubella used to be a major problem. It causes

cataract, glaucoma, heart defects and deafness. Cytomegalovirus :The infection is often fatal and

if not meningoencephalitis produce mental retardation.

Herpes simplex, varicella and human immunodeficiency viruses are other examples.

2- Toxoplasmosis3- Syphilis : leads to congenital deafness and

mental retardation.

Environmental factors Cont.

22))RadiationRadiation : : Ionizing radiation kills rapidly proliferating cells, producing any type of birth defect depending upon dose and stage of development. Ex. Atomic bomb on Hiroshima and Nagasaki .

Exposure of the pregnant woman to a large dose of x- ray can lead to microcephaly, spina bifida or cleft palate.

Environmental factors Cont.

3) Chemical agents:3) Chemical agents:There are many dangerous drugs, if have given to the pregnant female, can produce

congenital anomalies. Ex.: - Thalidomide (antinauseant sleeping pills) produce limb defects (phocomelia) and

heart malformations. - Diphenylhydantoin produce facial defects and mental retardation. Tetracycline (bone and teeth anomalies)Tetracycline (bone and teeth anomalies) Aspirin may cause harm in large doses.Aspirin may cause harm in large doses. Cocaine cause birth defect possibly to its effect as a vasoconstrictor that cause Cocaine cause birth defect possibly to its effect as a vasoconstrictor that cause

hypoxia.hypoxia. Alcohol cause fetal alcohol syndrome.Alcohol cause fetal alcohol syndrome.

Environmental factors Cont.

5)Hormones:5)Hormones: Androgenic agents (synthetic progestin to

prevent abortion) cause masculinization of the genitalia of female embryos.

Endocrine hormones as Diethylstilbestrol cause malformation of the uterus, uterine tubes, upper vagina, vaginal cancer and malformed testes.

Insulin which treat diabetes of the mother congenital anomalies.

Cortisone (in large doses) may cause cleft palate.

Environmental factors Cont.

6)Maternal Disease:6)Maternal Disease: Diabetes cause variety of

malformations as heart and neural tube defects.

7)Nutritional deficiency:7)Nutritional deficiency: particularly vitamins deficiency.

8)Heavy metals:8)Heavy metals: Eg: organic mercury.

PRENATAL DIAGNOSISPRENATAL DIAGNOSIS Methods of prenatal diagnosis are divided into invasive and non-Methods of prenatal diagnosis are divided into invasive and non-

invasive techniques.invasive techniques. Technique Time Disorders diagnosedTechnique Time Disorders diagnosed (in weeks)(in weeks) A. Non-invasive:A. Non-invasive: Maternal serum screen:Maternal serum screen: Alpha feto protein (AFP) 16 Neural tube defects (NTD)Alpha feto protein (AFP) 16 Neural tube defects (NTD) Triple test 16 Down syndromeTriple test 16 Down syndrome Ultrasound Ultrasound 18 Structural defects in many 18 Structural defects in many organs as CNS, heart, organs as CNS, heart, kidney, and limbs.kidney, and limbs.

B. Invasive:B. Invasive: - - Amniocentesis Amniocentesis 14-16 Chromosomal and metabolic 14-16 Chromosomal and metabolic abnormalities, and DNA abnormalities, and DNA analysis.analysis. - - Chorionic villus samplingChorionic villus sampling 10-12 As amniocentesis. 10-12 As amniocentesis. - - Fetal blood sampleFetal blood sample near term As amniocentesis + blood near term As amniocentesis + blood disorders.disorders.

Technique of Technique of amniocentesisamniocentesis

Technique of CVSTechnique of CVS

U/S showing polydactylyU/S showing polydactyly

U/S showing micrognathiaU/S showing micrognathia

U/S showing Umibilical hernia (associated with Trisomy 18 in 50% of cases)U/S showing Umibilical hernia (associated with Trisomy 18 in 50% of cases)

Fetal therapy The fetus during intrauterine life can receive

treatment such as:1- Fetal transfusion (administration of blood transfusion

to the anemic fetus in thalassemia). 2- Medical treatment of thyroid dysfunction or

congenital adrenal hyperplasia of the fetus.3- Fetal surgery: is possible due to advanced ultrasound

and surgical procedures eg: repair of hernia of the fetus or in case of hydrocphalus.

4- Stem cell transplantation and gene therapy: it is possible to transplant stem cells before 18 weeks of gestation of the fetus without rejection because the immunocompetence of the fetus doesn’t develop yet.