Congenital anomalies

Congenital anomalies. Dr Dharshnee Rama Chetty Anatomical Pathology.

Introduction. Congenital anomalies are also known as birth defects, congenital disorders or congenital malformations. Congenital anomalies can be defined as structural or functional anomalies (e.g. metabolic disorders) that occur during intrauterine life and can be identified prenatally, at birth or later in life eg hearing loss.

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

During the first 2 weeks of development, teratogenic agents usually kill the embryo or have no effect . During the organogenesis period (3rd – 8th weeks), teratogenic agents disrupt development and may cause major congenital anomalies. During the fetal period (9th week – 9th month) teratogens may produce morphological and functional abnormalities , particularly of the brain and eyes..

Causes of congenital anomalies. Genetic factors such as chromosomal abnormalities and mutant genes. Environmental factors e.g. the mother had German measles in early pregnancy will cause abnormality in the embryo. Combined genetic and environmental factors (multifactorial)..

Types of abnormalities. Malformations: morphologic defect of a part of an organ that has resulted from abnormal developmental process eg congenital heart disease, c left lip and/or cleft palate. 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. Deformations: due to mechanical forces that affect a part of the fetus over a long period. Ex: talipes equinovarus deformity(club-foot). Sequence : Cascade of events triggered by an abnormality, usually single eg oligohydromnios causing Potter’s sequence Syndrome: is a group of anomalies occurring together due to a common cause usually genetic eg Down Syndrome(Trisomy 21) ..

Causes of congenital malformations. Mutant genes Chromosome anomalies Multifactorial disorders - interaction between genetic predisposition & environmental factors Teratogenic agents Unknown.

The genetic factors leading to congenital anomalies may be due to chromosomal abnormalities, gene mutations or may be multifactorial. Chromosomal abnormalities occur due to: late maternal age at the time of pregnancy (leads to chromosomal non-disjunction),- radiation (causes chromosome deletions, translocations or breaks) viruses as German measles, autoimmune diseases, some chemical agents as anti-mitotic drugs..

Chromosomal abnormalities are classified into numerical and structural..

Aneuploidy (one or more chromosomes is added or missed) as in: Down syndrome (trisomy 21).

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

Turner syndrome ((45,X or a female missing one X), and Klinefelter syndrome (47,XXY or a male person with an extra X chromosome)..

Environmental factors. Infectious Agents: 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. Toxoplasmosis Syphilis : leads to congenital deafness and mental retardation..

Environmental factors Cont.. Radiation : 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.. Chemical agents: There are many dangerous drugs, if have given to the pregnant female, can produce congenital anomalies. Ex.:Thalidomide produce limb defects ( phocomelia ) and heart malformations. Diphenylhydantoin produce facial defects and mental retardation. Tetracycline (bone and teeth anomalies) Aspirin may cause harm in large doses. Cocaine cause birth defect possibly to its effect as a vasoconstrictor that cause hypoxia. Alcohol cause fetal alcohol syndrome..

Environmental factors Cont.. 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 Maternal Disease: Diabetes cause variety of malformations as heart and neural tube defects. Nutritional deficiency: particularly vitamins deficiency. Heavy metals: Eg : organic mercury..

PRENATAL DIAGNOSIS. Methods of prenatal diagnosis are divided into invasive and non-invasive techniques. Non-invasive: Maternal serum screen : Alpha feto protein (AFP) - Neural tube defects (NTD) Triple test - Down syndrome Ultrasound Structural defects in many organs as CNS, heart,kidney , and limbs. Invasive: Amniocentesis Chromosomal and metabolic abnormalities Chorionic villus sampling as amniocentesis..

Neural tube defects. Image result for neural tube defects.

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Definition. Failure of closure of the neural tube. Can occur at various levels. Can have widely varying severity. Most severe is anencephaly. Least severe is spina bifida occulta . Most clinically challenging is lumbo -sacral myelomeningocele..

Folate. Low serum folate correlated with NTDs Folate supplementation with 400-800 ug per day reduces incidence by 75%. Clearly, a sub-set of NTDs are not “folate dependent”..

Prenatal Detection. In developed countries, prenatal detection of severe NTD should approach 100%. Maternal serum AFP screening is efficient as a screening tool. Sonography is efficient at both screening and diagnosis..

Counseling. Outcome depends a lot on level. Lower lesions may result in relatively mild defects. Another issue is the related hydrocephalus, cerebellar malformation and long-term cognitive dysfunction..

Summary. Generally not genetic Recurrence risk is elevated over background but still low Prenatal detection is excellent but some cases can present a big counseling challenge..

Neural Tube Defects. Probably the most common congenital defect Some part of the neural tube or its coverings has not closed Occurs 21-28 days after conception Multifactorial aetiology High recurrence rate: associated with poor maternal nutrition Prevention : pre- conceptional folic acid.

Aetiology : multifactorial. Combination of genetic, environment & maternal factors Genetic - trisomy 13, triploidy Maternal diabetes Antiepileptic drugs Alcohol Antiepileptic drugs Phenytoin 6-30% embryopathy with NTD growth deficiency microcephaly facial dysmorphism developmental delay congenital malformations Valproate.

Prenatal diagnosis. Ultrasound Invasive tests : amniocentesis fetal cord blood sampling chorionic villus sampling Serum screening (maternal) e.g. AFP (alpha fetoprotein) at 16 weeks for NTD ( neural tube defect).

Spinal defects. Spina bifida is a birth defect in which there is incomplete closing of the spine and membranes Two types: spina bifida occulta and spina bifida cystica . Spina bifida cystica can then be broken down into meningocele and myelomeningocele Spina bifida occulta : vertebral defect with normal cord and membranes. usually lumbosacral. skin over the defect may show abnormal pigmentation, a hairy patch or a dermal sinus. meningocele : meningeal sac protrudes through a bony defect and is covered by intact skin meningomyelocele : skin overlying the sac ruptures exposing the abnormal meninges, nerve roots and abnormal/ incompletely formed cord.

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Image result for meningocele.

Meningomyelocele. Usually in lower thoracic, lumbar and upper sacral spine 80% have associated hydrocephalus Frequently have joint deformities or restriction of movement Absent anal sphincter and bladder enervation May die at birth, or develop ascending meningitis < 10%survive beyond 6 months without treatment.

Image result for meningomyelocele.

Cranial defects. Hydrocephalus Defined as presence of excessive amounts of CSF within the cranial cavity. Usually caused by obstruction to CSF flow - with dilatation of the ventricular system proximal to the obstruction Overproduction of CSF Defective reabsorption of CSF.

Hydrocephalus : Clinical. Macrocephaly Widely separated sutures Huge fontanelles Relatively small face Usually progressive resulting in intellectual impairment spastic paraplegia cerebellar ataxia.

Hydrocephalus : Causes. Arno l d Chiari malformation commonest cause in neonates obstruction at the foramen magnum with spina bifida Acquired due to inflammation or haemorrhage, obstruction of aqueduct of Sylvius Mutant genes Incidence 1: 1000 Treated with ventricular shunt with one-way valve to drain CSF into peritoneum.

Cranial defects. Anencephaly : cranial vault missing and base of skull poorly formed. the coverings of the brain fail to develop and the developing brain is exposed to amniotic fluid. cerebrum and cerebellum are usually absent. the base of the skull is covered by disorganised brain tissue and blood vessels called the area cerebrovasculosa.

Anencephaly. Cranial end of the neural tube fails to close Acrania ( absence of cranial bones) 50% associated with craniorachischisis both the brain and spinal cord remain open to varying degrees.

The End. Thank you.