2. TERMINOLOGIES
Maternal related to mother, especially during pregnancy
Prenatal - Before birth of the baby
Defects - Incompleteness, inadequate, imperfection.
Conceive- Become pregnant
Termination - Coming to an end
Viability - The capacity of living
3. CONGENITAL ANOMALIES AND
DYSMORPHIC SYNDROMES
Congenital anomaly (birth defect/con genital defect/congenital disorder):
The term congenital means "born with". All types of structural
abnormalities or defects that are present at birth are termed as congenital
anomaly.
A malformation is a primary (or intrinsic) structural defect occurring
during the development of an organ or tissue.
Dysmorphology is the study of malformations arising from abnormal
embryogenesis.
4. CLASSIFICATION OF BIRTH DEFECTS
➢ Malformations may involve one organ/system or multiple systems.
➢ Single system defects (single abnormalities): Single abnormalities
may have a genetic or non genetic basis. For examples, congenital
heart defects (such as ventricular or atrial septal defects), cleft lip
and/or palate and neural tube defects.
➢ Multiple malformation syndromes (multiple abnormalities): It
consists of defects in two or more systems and is more likely to be
due to chromosomal abnormalities.
➢ Syndrome: When a combination of congenital abnormalities occurs
together repeatedly in a consistent pattern due to a single
underlying cause, it is termed as "syndrome".
5. CAUSES OF CONGENITAL ANOMALIES
➢ In 60-70% of the cases, the exact cause is not known (idiopathic).
➢ The common causes can be grouped into three major categories:
➢ Genetic,
➢ Environmental,
➢ Multifactorial origin (due to interaction of many genes with other
factors).
7. GENETIC FACTORS
➢ It plays a role in some birth defects. Genetic
causes of congenital anomalies can be divided
into two main categories:
➢ Those associated with chromosomal aberrations.
➢ Those arising from single-gene mutations ("Mendelian
disorders").
8. GENETIC FACTORS
Chromosomal Birth Defects
➢ Abnormalities in the number or structure of chromosomes can
cause birth defects and is responsible for about 6% of
congenital abnormalities.
➢ Severe chromosomal disorders lead to spontaneous
abortion/miscarriage. For examples of birth defects due to
chromosomal disorders include:
➢ Down syndrome (an extra copy of chromosome 21).
➢ Turner syndrome (girl with a missing part or whole X
chromosome).
➢ Klinefelter syndrome (a boy has two or more X
chromosomes).
9. GENETIC FACTORS
Single-gene defects
➢ Deletion or mutation in single gene can cause congenital
anomalies.
➢ Single-gene mutations follow Mendelian patterns of inheritance
and are responsible for about 7.5% of all congenital anomalies.
➢ Approximately, 90% are inherited in an autosomal dominant or
recessive pattern, while the remainder in an X-linked pattern.
➢ Single-gene defects may involve only one organ (system) or many
organs
10. ENVIRONMENTAL FACTORS
➢ An agent which causes a birth defect (structural abnormality) or
malformations of an embryo or fetus is known as a teratogen.
➢ Teratology is the study of developmental anomalies.
➢ Developmental defects induced by teratogens are potentially
preventable.
➢ If mother is exposed to teratogens during pregnancy, it can
produce fetal death, growth retardation, fetal malformation, or
functional impairment.
➢ The teratogens may be drug, chemical, physical or biological
agents.
11. ALCOHOL
➢ It is the most widely used teratogen. Alcohol abuse by the mother
(during pregnancy) causes several structural anomalies.
➢ Cognitive and behavioral defects in the fetus, collectively termed
fetal alcohol spectrum disorders (FASDs).
➢ The severely affected infants with FASDs have growth retardation.
microcephaly, atrial septal defect, short palpebral fissures, and
maxillary hypoplasia, and this classic teratogenic phenotype is
labeled as fetal alcohol syndrome.
12.
13. THALIDOMIDE
➢ It was once used as a tranquilizer to treat morning sickness.
➢ It was found to be teratogenic when administered between the
28th and 50th days of pregnancy.
➢ Many children born to mothers exposed to thalidomide presented
with skeletal deformities (limb abnormalities) and defects in other
organs, mainly the ears and heart.
➢ Typically, they had short and malformed limbs which resembled
the flippers of a seal (phocomelia). The children had normal
intelligence.
15. SMOKING & CHEMICALS
➢ Nicotine derived from cigarette smoke has not been proven to be a
teratogen. However, it can lead to spontaneous abortions,
premature labor and placental abnormalities.
➢ Few chemicals are known to be teratogenic. For example, exposure
to organic solvents (chemicals that dissolve other substances such
as degreasers, paint thinners and varnish removers), and high
levels of exposure to pesticides may increase the risk of birth
defects.
16. MATERNAL INFECTIONS
➢ Several maternal infections can interfere with embryogenesis and
fetal development.
➢ The developing brain, eyes and ears are particularly susceptible to
damage by infection.
➢ Viral infections: Certain viral infections during pregnancy can
cause birth defects. The viruses include rubella, cytomegalovirus,
herpes simplex, varicella-zoster, influenza, mumps, human
immunodeficiency virus (HIV), and enterovirus infections. The
main factor which determine the risk is the gestational age at
which the viral infection
17. MATERNAL INFECTIONS
➢ Several maternal infections can interfere with embryogenesis and
fetal development.
➢ The developing brain, eyes and ears are particularly susceptible to
damage by infection.
18. MATERNAL INFECTIONS
➢ Viral infections: Certain viral infections during pregnancy can
cause birth defects. The viruses include rubella, cytomegalovirus,
herpes simplex, varicella-zoster, influenza, mumps, human
immunodeficiency virus (HIV), and enterovirus infections.
➢ The main factor which determine the risk is the gestational age at
which the viral infection occurs in the mother.
➢ Maternal infection early in gestation may cause structural
abnormalities of the central nervous system and congenital heart
disease.
19. MATERNAL INFECTIONS
➢ Toxoplasmosis: Maternal infection with the parasite causing
toxoplasmosis has risk of infecting the fetus.
➢ The TORCH test is a blood test which measures infectious
disease antibody titer against groups of chronic infections:
toxoplasmosis, rubella. cytomegalovirus (CMV), and herpes
simplex virus (HSV).
➢ Sexually transmitted infections (STIs): STIs in the mother can
damage the fetus and newborn. For example, untreated syphilis can
cause stillbirth, newborn death or bone defects.
20. PHYSICAL AGENTS
➢ It is mutagenic, carcinogenic and also teratogenic.
➢ It includes electromagnetic waves (X-ray and gamma rays), high
energy particles and atomic radiation.
➢ Exposure to heavy doses of ionizing radiation (as in radiotherapy)
during early pregnancy (2-5 weeks after conception) leads to
microcephaly.
➢ Blindness, skull defects, spina bifida and other deformities in the
developing fetus.
21. MATERNAL DISORDERS AND ILLNESS
➢ Several maternal disorders are associated with an increased risk of fetal
malformations.
➢ Maternal diabetes: The risk of congenital mal formations in the fetus of
insulin-dependent diabetic pregnant is higher. Non-insulin dependent
diabetes and gestational diabetes do not have an increased risk.
➢ Phenylketonuria (PKU): All women with phenylketonuria should
consume low phenylalanine diet both before and during pregnancy. A
high serum level of phenylalanine in pregnant woman will result in
serious fetal abnormalities such as microcephaly, congenital heart defects
and mental retardation in almost all the children. Affected babies are
given a special diet that prevents mental retardation.
22. MULTIFACTORIAL INHERITECE
➢ Some birth defects are caused by a combination of genes and
environmental exposures.
➢ Multifactorial inheritance is defined as the interaction of genes
with environmental factors. Examples of multifactorial birth
defects include: Cleft lip/palate (opening in the lip and/or roof of
the mouth).
➢ Neural tube defects (NTDs) (serious birth defects of the brain and
spinal cord, including spina bifida and anencephaly), the incidence
of which can be reduced by consumption of folic acid during
periconceptional period.
➢ Congenital heart defects.
23. PREVENTION OF CONGENITAL ANOMALIES
Preconception Visit
➢ Identify the diseases: These include: chronic illness like diabetes,
epilepsy and hypertension.
➢ Advice on lifestyle: These include: Quitting smoking, avoiding
alcohol and any medications during pregnancy which are
teratogenic or not safe.
➢ Check for vaccination especially measles, mumps and rubella
(MMR).
➢ Genetic counseling.
24. PREVENTION OF CONGENITAL ANOMALIES
➢ During Pregnancy All pregnant women should take a daily multi
vitamin containing folic acid, to reduce the risk of neural tube
defects (spina bifida and anencephaly).
25. CONSANGUINITY
➢ It refers to relationship by blood (being from the same family) or
by a common ancestor.
➢ Definition: Consanguineous marriage is defined as marriage
between close blood relatives who have at least one common
ancestor.
➢ Though not morally permissible, they do occur in some
communities.
➢ In Arab populations, the most common type of consanguineous
marriage occurs between first cousins who are the children of two
brothers.
➢ In the Indian subcontinent, uncle-niece marriages are the most
commonly encountered form of consanguineous relationships.
26. RISK OF CONSANGUINITY
➢ Congenital malformations: The child of consanguineous
marriage is associated with an increased incidence of genetic
disorders and congenital malformations.
➢ Phenotypic characteristics: Blindness, hearing loss and seizures
are much more common than in the general population.
➢ Metabolic disorders: Phenylketonuria is three times more
common than in general population.
➢ Other disorders: These include mental retardation, primary
amenorrhea and a slightly increased risk of a multifactorial
disorder.
27. ATOPY
➢ The term 'atopy' (meaning out of place or strangeness) was coined by
Coca (1923) to refer to naturally occurring familial hypersensitivity in
humans.
➢ Atopy is a hereditary predisposition toward developing type I
hypersensitivity reactions on exposure to specific antigens.
➢ These include allergic disorders such as hay fever, asthma, or chronic
urticaria.
➢ Allergy is defined as abnormally high sensitivity to antigens known as
allergens. These allergens may be inhaled (e.g., pollen, house dust or
microorganisms) or ingested (e.g., eggs, milk, or other foods).
➢ Some of the allergens cause disease when they come in contact with the
surface like skin or conjunctiva and are called as contact allergens.
➢ The antigens causing atopy (allergens) induce IgE type of antibodies.
These antibodies were formerly known as 'reagin' antibodies.
28. PRENATAL NUTRITION AND FOOD ALLERGIES
➢ Allergic diseases are common cause of illness. Diet during early
childhood is an important factor determining the development of
allergy.
➢ The factors which decrease the incidence of allergy, particularly in
high-risk infants with a parental history of atopy are:
➢ Maternal Diet & Atopy
➢ Infant Nutrition
➢ Low Exposure to Environmental Agents
➢ Identification of High Allergy Risk Newborns
29. Maternal Diet & Atopy
➢ The risk of atopy in the child can be reduced if the mother avoids
allergenic foods during pregnancy and lactation. The examples for
common food with allergens include milk, egg, fish and peanuts.
30. Infant Nutrition
➢ Important relationship exists between infant nutrition and atopy.
Breastfeeding and its benefit in atopy:
➢ Exclusive breastfeeding: It can lower incidence of atopic disease and food
allergy. Highest prevalence of atopy was noted in children who had little or
no breastfeeding. The partial protective effect of breastfeeding may last as
long as child attains 18. years of age.
➢ Advantages of breast feeding in atopy are:
➢ The baby formulas contain proteins which may be allergens. If breast-fed, there is no
need of baby formulas.
➢ Reduces frequency of gastrointestinal infection, which can act as an adjuvant.
➢ Human breast milk contains anti inflammatory factors and antibodies.
31. Infant Nutrition
➢ Prolonged breastfeeding: If exclusive breast feeding is done beyond 4
months, it reduces the occurrence of allergic disease. More prolonged the
breastfeeding, greater is the protection against allergy.
➢ Milk supplement: Some infants cannot be breast-fed and require a milk
supplement. The supplement by a hypoallergenic hydrolysate milk formula is
distinctly better than a conventional cows' milk formula or a soya milk
formula.
➢ Delayed introduction of allergic solid food: Delayed introduction of
allergenic solid foods like dairy products, eggs, fish, nuts and soya bean in
the child's diet reduces the risk of atopy.
32. IDENTIFICATION OF HIGH ALLERGY RISK
NEWBORNS
➢ Infant who has a high-risk of developing atopic disease should be identified.
It will help in implementing preventive measures for allergy and also to
motivate the parents to follow those measures.
➢ Parents with atopy: If both parents have atopic disease, the risk of developing
allergies in the child is greater than if only one of them is affected.
➢ IgE level in cord blood: If cord-blood immunoglobulin (Ig) E is elevated, the
risk is high irrespective of family history. Conversely, low cord-blood IgE is
associated with relatively low risk.
➢ Reduction in number of CD8+ suppressor cells: CD8+ cells play an important
immuno regulatory role in IgE production. Reduction in CD8+ suppressor cells
during the first few days of life, increase the risk of allergy.
33. MATERNAL AGE
➢ Age of mother has an influence on the pregnancy and fetus. Advanced
maternal age (AMA) is defined as any expectant mother of age 35 years or
above by the time she delivers.
➢ Majority of women over the age of 35 years have healthy pregnancies and
healthy babies.
➢ Higher risk of genetic abnormalities: As maternal age increases there is an
increased risk of Down's syndrome and other chromosomal abnormalities.
Advanced maternal age is one of the indications for prenatal testing.
➢ Decreased fertility: In women, fertility begins to decrease from beginning in
their early thirties. The conception is delayed in women older than 35 years
when compared to those younger than 35.
➢ Risk of twins: Advanced maternal age is as sociated with higher risk of having
a naturally conceived (without fertility treatment) twin pregnancy. Twins can
be identical or non identical-monozygotic (MZ) (uniovular) or dizygotic (DZ)
(biovular)-depending on whether they originate from a single conception or
from two separate conceptions
34. MATERNAL AGE
➢ Diseases associated with advanced age: As age increases, the
risk of developing diabetes or high blood pressure, during
pregnancy also increases.
➢ Gynecological problems such as pelvic infection, tubal damage,
endometriosis, fibroids, ovulation problems, etc. tend to increase
with age and interfere with fertility.
35. MALE FACTORS IN INFERTILITY
➢ Infertility is the failure to conceive after regular unprotected
sexual intercourse after a given period of time, usually one year in
humans.
Primary vs. secondary infertility:
➢ Primary infertility means that couples have never been able to
conceive.
➢ Secondary infertility is difficult to conceive after already having
conceived (either carried the pregnancy to term or had a
miscarriage).
➢ The cause of reduced fertility and infertility may be in the male or
female partner. The environmental factors are important, but
genetic factors can also be involved.
36. MALE FACTORS IN INFERTILITY
➢ Male Factors in Infertility Male infertility accounts for 40-50%
cases of infertility.
Defect in Sperm Production
➢ Male infertility is commonly due to failure in spermatogenesis
(sperm production).
➢ Azoospermia is defined as absence of sperm in the ejaculate. It
may be due to obstruction (blockage) of sperm from testis to
terminal urethra.
➢ Oligospermia is defined as sperm count from testis below the
normal limit.
37. GENETIC FACTORS WHICH CAUSE SPERM
ABNORMALITIES
Abnormalities in chromosome number or structure
➢ Male with chromosomal abnormalities has a greater risk of
having children with chromosomal abnormalities and also
infertility.
➢ Abnormalities in chromosome number: Klinefelter syndrome
(47,XXY) is associated extra X chromosome.
➢ Abnormalities in chromosome structure: These include
translocations (e.g. Robertsonian translocations) and pericentric
inversions.
38. GENETIC FACTORS WHICH CAUSE SPERM
ABNORMALITIES
Genetic defects on the Y chromosome
➢ The Y-chromosome contains many genes required for
spermatogenesis.
➢ Y chromosome microdeletion (YCM) is a family of genetic
disorders caused by deletion of very tiny/small areas (genes) in
the Y chromosome. These areas of deletion are known as region
are one of the causes of male infertility.
39. GENETIC FACTORS WHICH CAUSE SPERM
ABNORMALITIES
Monogenic disorders
➢ Genetic conditions with associated infertility: These are relatively
rare and include: Noonan's syndrome, myotonic dystrophy,
Kallmann syndrome, partial androgen in sensitivity (Reifenstein
syndrome), adult polycystic kidney disease, and Kartagener/
immotile cilia syndrome.
Autosomal gene mutations
➢ Cystic fibrosis is a monogenic inherited disorder caused by a
mutation in the CFTR genes. It may cause reduced fertility in
males.
40. GENETIC FACTORS WHICH CAUSE SPERM
ABNORMALITIES
Epigenetic Factors
➢ Changes in the genetic material that do not alter the basic DNA
sequence are called epigenetic factors.
➢ Epigenetic abnormalities include:
➢ Defects in telomeres: Telomeres are important in
spermatogenesis.
➢ Defects in mitochondrial DNA: It can impair the movement of
sperm.
41. GENETIC FACTORS WHICH CAUSE SPERM
ABNORMALITIES
Non Genetic Causes of Male Infertility and poor
➢ Pretesticular causes: Pretesticular causes include poor hormonal support
general health. It is suggested that tobacco products in cigarette smoke
may kill sperms.
➢ Testicular factors: Testis may produce semen of low quantity and/or
poor quality despite adequate hormonal support. Apart from genetic
abnormalities, other causes of infertility are testicular cancers,
undescended testis, varicocele and mumps.
➢ Post-testicular causes: Any abnormalities in the organs involved in
transport of sperm from testis to urethra may cause infertility despite
normal sperm production by testis. These include defects of the genital
tract and problems in ejaculation.
42. FEMALE FACTORS IN INFERTILITY
Genetic Causes
Many cases of female infertility are due to genetic factors.
Chromosomal abnormality: It is associated with infertility and increased
risk of spontaneous abortion.
Inherited genetic diseases: These are rare and may be due to abnormal
genes or mutations.
X mutations: Premature ovarian failure or early menopause may be found
in carriers of fragile X mutations.
43. FEMALE FACTORS IN INFERTILITY
Non-Genetic Causes
➢ Defect in ovulation: Infertility may be due to defect in maturation or
release of ova from ovary.
➢ Blockage of fallopian tube: It may be caused by infections such as
chlamydia, tuberculosis and prevent the transport of ova from ovary to
uterus.
➢ Diseases of uterus: For example, endometriosis (endometrial glands and
stroma is found outside the uterine cavity).
➢ Other factors: For example, over- or under weight.
44. RECURRENT SPONTANEOUS ABORTIONS
➢ Spontaneous abortions (miscarriage) is the expulsion from the mother's
womb of an embryo or fetus weighing 500 g or less when it is not capable
of independent survival.
➢ Physical defects of the uterus (e.g., submucosal leiomyomas, uterine
polyps, or uterine malformations) may be one of the cause of spontaneous
abortion.
➢ Definition: Recurrent spontaneous abortions (RSAs) is defined as
sequence of two or more consecutive abortions before 20 weeks of
pregnancy.
45. CAUSES RECURRENT SPONTANEOUS
ABORTIONS
➢ Causes of recurrent spontaneous abortions are complex and in majority of
the cases it is not known. Sometimes more than one factor may be
responsible.
➢ Genetic factors: Chromosomal abnormality in parents is one of the
causes of recurrent spontaneous abortions. The most common structural
abnormality is translocation. Sometimes mosaicism for sex chromosome
can lead to recurrent spontaneous abortions.
➢ Immunologic causes: These may be classified as autoimmune and
alloimmune factors. Autoimmunity: Presence of autoantibodies in mother
can cause recurrent spontaneous abortions.
46. CAUSES RECURRENT SPONTANEOUS
ABORTIONS
➢ Alloimmunity: This may be mainly due to sharing of human leukocyte
antigen (HLA) between parents.
➢ Clotting factor mutations: For example, Factor V Leiden protein, C
resistance and homocystinuria.
➢ Endocrine and metabolic factors:
➢ Poorly controlled diabetes.
➢ Presence of antithyroid antibodies.
➢ Luteal phase defect with diminished levels of progesterone.
➢ Hyper secretion of luteinizing hormone.
47. INVESTIGATIONS FOR RECURRENT SPONTANEOUS
ABORTIONS (if the cause is genetic
➢ Investigations for the Genetic Causes Include
➢ Histological examination of placenta.
➢ Karyotyping of the aborted fetus.
➢ Karyotyping of both husband and wife.
➢ If chromosomal abnormality is detected in the couples or in the aborted
fetus, genetic counseling should be undertaken.
49. NEURAL TUBE DEFECTS
➢ During 3rd or 4th weeks of pregnancy (first month of embryonic life),
specialized cells on the dorsal side of the fetus begin to fuse and form the neural
tube.
➢ Sometimes, the neural tube. may not close completely or after successful closure
it may reopen.
➢ These malformations resulting from defective closure of the developing neural
tube are known as neural tube defects (NTD). These malformations involve
neural tissue, meninges, and overlying bone or soft tissues.
50.
51. TYPES OF NEURAL TUBE DEFECTS
➢ Most of the neural tube defects have serious consequences.
➢ Defect in the upper end of neural tube: A defect occurring at the upper end of the
developing neural tube results in either anencephaly or an encephalocele.
➢ Anencephaly (without brain): It occurs when the head end of the neural tube
fails to close. It is characterized by the absence of a major portion of the brain
and skull. Infants either die within the uterus (stillborn) or die within a few
hours or days after birth.
52.
53. TYPES OF NEURAL TUBE DEFECTS
➢ Encephalocele: It is a neural tube defect characterized by sac-like protrusion of
the brain through the opening in the skull. It is due to the incomplete closure of
the cranium.
54. TYPES OF NEURAL TUBE DEFECTS
➢ Defect in the lower end of neural tube - A defect occurring at the lower end of
the developing neural tube leads to a spinal lesion such as a lumbo-sacral
myelocele or meningomyelocele.
➢ Spina bifida: It is the most common neural tube defect which involves the
spinal cord. It is caused by failure of closure of the lower portions of the neural
tube. Spina bifida may be an asymptomatic bony defect or it may present with a
severe malformation associated with an overlying meningeal out pouching.
➢ There are two types of Spina Bifida
➢ Spina Bifida Cystica
➢ Meningocele
➢ Myomeningocele
➢ Spina Bifida Occulta
55.
56. TYPES OF NEURAL TUBE DEFECTS
➢ Meningocele: It is characterized by extension of only meninges through a defect
in the spinal cord.
➢ Myelomeningocele (or meningomyelocele): It refers to the extension of spinal
cord tissue through a defect in the vertebral column. It occurs most commonly in
the lumbosacral region.
57. NEURAL TUBE DEFECTS CAUSES
➢ Neural tube defects are caused by multifactorial inheritance. It is due to
combination of genetic, environmental and nutritional factors during early
embryonic development.
➢ Genetic factors: Trisomy 18 and 13 are associated with NTDs in about 5-10%
of cases.
➢ Environmental factors: Prenatal exposure to certain drugs which cause
congenital defects.
➢ Nutritional factors: Folic acid deficiencies and folate antimetabolites (such as
methotrexate) are associated with increased incidence of neural tube defects.
➢ Others: These include maternal diabetes, maternal obesity, poor socioeconomic
status, multiparity and cigarette smoking.
58. ROLE OF FOLIC ACID IN LOWERING THE RISK
OF NEURAL TUBE DEFECTS
➢ Folic acid is an important nutritional factor required for DNA and RNA
synthesis.
➢ Folic acid plays a role during the closure of the neural tube and its deficiency is
important factor in neural tube defects.
➢ Taking folic acid prior to conception and during the first 3 months of pregnancy
significantly reduces the risk, but does not completely prevent it.
59. ROLE OF FOLIC ACID IN LOWERING THE RISK
OF NEURAL TUBE DEFECTS
Prevention
➢ To prevent the first occurrence of neural tube defects, all women planning a
pregnancy should adopt the following:
➢ Diet of women planning a pregnancy should be supplemented with folic acid.
➢ Processed foods such as bread, cereals, flour and other grain products, which are
fortified with folic acid, should be used.
➢ Consume more folate-rich foods and avoid overcooking which destroys the folic
acid.
➢ As soon as women become pregnant, she should be immediately given folic acid
daily. This should be continued until the 12th week of pregnancy.
➢ Dosage – 400 mcg Daily up to 12 weeks.
60. ROLE OF FOLIC ACID IN LOWERING THE RISK
OF NEURAL TUBE DEFECTS
➢ To prevent recurrence of neural tube defects in the child of parents who had a
previous child with NTD, the mother should take folic acid daily and should
continue until the 12th week of pregnancy.
➢ Antenatal diagnosis: It is based on imaging and the screening of maternal blood
samples for elevation of α-fetoprotein.
62. DOWN SYNDROME (TRISOMY 21)
➢ Down syndrome was first described by Dr John Langdon Down.
➢ It is the most common chromosomal disorder and is a leading cause of mental
retardation.
➢ The incidence of Down syndrome in newborns is about 1 in 700. About 95% of
these individuals have trisomy 21 (extra copy of chromosome 21), resulting in
chromosome count of 47 instead of normal 46.
➢ The parents of such children are normal and have a normal karyotype.
63. ETIOLOGY
➢ Maternal age: It has a strong influence on the incidence of trisomy 21.
Children of older mothers have much greater risk of having Down
syndrome.
➢ Other factors: Increased incidence maybe associated with exposure of
mother to pesticides, electromagnetic fields, anesthetic drugs, alcohol and
caffeine.
64. MECHANISM OF TRISOMY 21
➢ The three copies of chromosome 21 in somatic cells cause Down
syndrome.
➢ It may be due to:
➢ Nondisjunction in the first meiotic division of gametogenesis and is
responsible for trisomy 21 in most (95%) of the patients.
➢ Robertsonian translocation of an extra long arm of chromosome 21 to
another acrocentric chromosome causes about 5% of cases.
➢ Mosaicism is responsible in about 1% of cases.
65. CLINICAL FEATURES
➢ Diagnosis of Down syndrome is usually apparent at the time of birth by
the infant's characteristic craniofacial appearance.
➢ The diagnosis is confirmed by cytogenetic analysis.
➢ Characteristic features appear as the child grows.
➢ Mental status: Children are mentally retarded with low IQ (25 to 50).
66. CLINICAL FEATURES
➢ Craniofacial features: The diagnostic clinical features are as follows:
➢ Flat face and occiput, with a low-bridged nose, reduced interpupillary
distance and oblique palpebral fissures.
➢ Epicanthal folds of the eyes impart an oriental appearance (obsolete term
mongolism).
➢ A speckled appearance of the iris (Brush field spots)Enlarged and
malformed ears.
➢ A prominent tongue (macroglossia), which typically lacks a central
fissure and protrudes through an open mouth.
68. CLINICAL FEATURES
➢ Heart: Congenital cardiac anomalies and are responsible for the majority of the
deaths in infancy and early childhood.
➢ The cardiac defects are:
➢ Septal and AV defect: These defects may involve atrial septum (atrial septal
defect), ventricular septum (ventricular septal defect), and one or more
atrioventricular (AV) valves.
➢ Other cardiac anomalies: Tetralogy of Fallot and Patent ductus arteriosus.
➢ Skeleton: These children are small because of shorter bones of the ribs, pelvis,
and extremities.
➢ The hands are broad and short and show a simian crease (a single transverse
crease across the palm).
➢ The fifth finger curves inwards.
69. CLINICAL FEATURES
➢ Gastrointestinal tract: It may show esophageal/ duodenal stenosis or
atresia, imperforate anus and Hirschsprung disease (megacolon).
➢ Reproductive system: Men are sterile because of spermatogenesis arrest.
➢ Immune system: Affected children are susceptible to infections due to
defective immunity.
➢ Endocrine system: Antithyroid antibodies may cause hypothyroidism.
➢ Hematologic disorders: They have increased risk of acute myeloid or
lymphoblastic leukemia.
➢ Neurologic disorders: All patients older than age 40 years show
neuropathologic changes characteristic of Alzheimer disease (a
degenerative disorder of the brain).
