Anitha B-Presented Prenatal, Maternal factors influencing the Genetic Defect and Diseases

1. PRESENTATION
ON
Maternal, Prenatal factors
influences on Genetic Defects
& Diseases
Ms.Anitha B Vinothkumar
Skylark Institute of Nursing
Howrah
West Bengal

2. Maternal Age
• Advanced maternal age is defined as any expectant
mother of age 35 years or above by the time she delivers.

3. Maternal Age
• Age of the mother has an influence on the pregnancy and fetus.
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.

4. Maternal Age
• 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.

5. Maternal Age
• Risk of Twins:
• Advanced maternal age is associated with higher risk of
having a naturally conceived (without fertility treatment)
twin pregnancy.

6. Maternal Age
Diseases associated with advanced age:
• Diabetes or high blood pressure
• Gynaecological problems: eg. Pelvic infection, tubal
damage, endometriosis, fibroids, ovulation problems etc.
tend to increase with age and interfere with fertility.

7. Diseases associated with advanced
age:
• Gynaecological problems:
Pelvic Infection Fibroids

8. Diseases associated with advanced
age:
• Gynaecological problems:
Endometriosis PCOS

9. Other features of advanced age
• Libido (sexual desire) will decrease with age
• Endometrial receptivity will decrease with the age

10. Other features of advanced age
• Though advanced father’s age (Paternal) age has an
adverse effect, it is not as much as maternal age.

11. Infertility
• Definition:
Infertility is the failure to conceive after regular
unprotected sexual intercourse after regular unprotected
sexual intercourse after a given period of time, usually 1
year in humans.
Types:
•Primary
•Secondary

12. Infertility
• -Primary:
• It means that couples have never been able to conceive.
• -Secondary:
• It is difficult
conceived(either
miscarriage).
to conceive after
the pregnancy
already having
to term or had a

13. Infertility
• 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.

14. Male Factors in Infertility-(40-50%)
• Defect in sperm Production:
• - Due to failure in the spermagenesis:
□Azoospermia- is defined as absence of sperm in the
ejaculate. It may be due to obstruction of the passage of
sperm from testis to terminal urethra.
□Oligospermia-is defined as sperm count below the
normal limit.

15. Male Factors in Infertility-(40-50%)
• 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 the chromosome number:
• Eg.Klinefelter syndrome (47, XXY) is associated extra X
chromosome.

16. Male Factors in Infertility-(40-50%)
• 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 the chromosome number:
• Eg.Klinefelter syndrome (47, XXY) is associated extra X
chromosome.

17. Male Factors in Infertility-(40-50%)
Genetic Factors which cause sperm abnormalities:
-Abnormalities in the chromosome structure:
It includes translocation & pericentric inversion.
Eg.Robertsonian translocations

18. Male Factors in Infertility-(40-50%)
Genetic defect on the Y chromosome:
□Y chromosome micro deletion is a family genetic disorders caused by
deletion of very tiny/small areas (genes) in the Y chromosome.
• Monogenic Disorders:
• -Genetic conditions with associated infertility: Rare
• Eg. Kartagener/immotile cilia syndrome
• - Autosomal gene mutations: Cystic fibrosis is a monogenic inherited
disorder caused by a mutation in the CFTR genes Cystic fibrosis
transmembrane conductance regulator).

19. Male Factors in Infertility-(40-50%)
Monogenic Disorders:
• -Genetic conditions with associated infertility: Rare
• Eg. Kartagener/immotile cilia syndrome
• - Autosomal gene mutations: Cystic fibrosis is a monogenic inherited
disorder caused by a mutation in the CFTR genes.

20. Male Factors in Infertility-(40-50%)
• Epigenetic Factor:
• Changes in the genetic material that do not alter the basic DNA
sequence are called epigenetic factors. Its abnormalities include,
❑ Defects in telomeres
❑ Defect in mitochondrial DNA

21. Male Factors in Infertility-(40-50%)
• Non-Genetic Causes of Male Infertility:
• Pretesticular cause: It Includes,
✔ Poor hormonal support and poor general health
• Testicular factors: Testis may produce semen of low quantity and /or
poor quality.
✔ Testicular cancers, undescended testis, varicocele and mumps.

22. Male Factors in Infertility-(40-50%)
• Non-Genetic Causes of Male Infertility:
• Post testicular causes:
✔ Defects of genital tract and problems in ejaculation.
✔ Any abnormalities in the organs involved in transport of sperm from
testis to urethra may cause infertility.

23. Female Factors in Infertility
• Unknown
• Genetic Causes
• -Chromosomal abnormality
• -Inherited Genetic Diseases
• -X Mutations
Non-Genetic Causes:
• -Defect in Ovulation
• Blockage of Fallopian tube: Infections Like Chlamydia, TB and prevent the
transport of ova from ovary to uterus.
• Diseases of Uterus: eg. Endometriosis
• Other factors: eg. Over or under weight

24. RECURRENT SPONTANEOUS ABORTION
• Spontaneous Abortion:
It is the expulsion from the mother’s womb of an embryo or fetus
weighing 500g or less when it is not capable of independent survival.
Recurrent Abortion:
Definition:
• Defined as sequence of two or more consecutive abortions before 20
week of pregnancy.

25. Causes
• Majority of the cases are unknown
• Genetic Factors: Chromosomal abnormalities of the
parents (Translocation)
• Immunologic causes:
• -Auto immunity
• -Alloimmunity
• Clotting factor Mutation: eg. Factor V Leiden protein, C
resistance and homocystinemia

26. Causes
• Endocrine and metabolic factors:
• -Poorly controlled Diabetes
• -Presence of anti thyroid antibodies
• -Luteal phase defect with diminished levels of progesterone
• -Hyper secretion of LH
• Genital tract Infections
• Physical defects of the uterus: eg.Submucosal leiomyomas, uterine
polyps or uterine malformations.

27. Investigations for the genetic disease
• Histological examination of placenta
• Karyotyping of the aborted fetus
• Karyotyping of both husband and wife

28. NEURAL TUBE DEFECTS AND ROLE OF FOLIC ACID IN
LOWERING THE RISKS
• During 3rd or 4th week of pregnancy, specialized cells in the dorsal
side of the fetus begin to fuse and form 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.

29. Types:
• Defect in the Upper end of the Neural Tube:
• -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 (stillborns) or die within a few hours
or days after birth.

30. Types:
• Defect in the Upper end of the Neural Tube:
• -Encephalocele: Characterized by sac-like protrusion of the brain
through the opening in the skull. Due to incomplete closure of the
cranium.

31. Defect in the Lower end of the Neural
tube:
• Spina Bifida:
• 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.

32. Defect in the Lower end of the Neural
tube:
Meningocele: It is characterized by extension of only
meninges through a defect in the spinal cord.
• Myelomeningocele/Meningomyelocele:
• It refers to the extension of the spinal cord tissue through
a defect in the vertebral column.

33. Causes- Multifactorial inheritance
• Genetic Factors:
• Trisomy 18 and 13 are associated with NTDs in about 5-10 % of
cases.

34. Causes- Multifactorial inheritance
• Environmental factors: Prenatal exposure to certain drugs.
• Nutritional factors: Folic acid deficiencies and folate
antimetabolites(such as methotrexate)

35. Causes- Multifactorial inheritance
• Others: Maternal DM, Maternal Obesity, Poor socio economic status,
Multi parity and cigarette smoking

36. Role of Folic acid in lowering the Risk of Neural
Tube defects
• Folic acid is important nutritional factor required for DNA
and RNA synthesis.
• Prevention
• Diet
• Supplementation

37. Down syndrome
• - Described by Dr.John Langdon Down
It is the most common chromosomal disorder and is
leading to mental retardation.
• Incidence:
• 1 in 700.

38. Etiology and Pathogenesis
• Maternal age
• Other factors
• Exposure of the mother to pesticides
• Electromagnetic fields
• Anesthetic drugs
• Alcohol
• Caffeine

39. Mechanism of Trisomy 21
• Non disjunction (95%)
• Robertsonian translocation(4%)
• Mosaicism(1%)

40. Mechanism of Trisomy 21
• Non disjunction (95%)
• Robertsonian translocation(4%)
• Mosaicism(1%)

41. Clinical Features
• Mental status: Low IQ (25050)
• Craniofacial features:
• Flat face & Occiput
• Epicanthal folds of the eyes
• A Speckled appearance of the iris
• Enlarged and malformed ears
• A prominent tongue

42. Clinical Features
• Brain: Mental retardation
• Heart: Congenital cardiac anomalies

43. Clinical Features
• Skeleton: Small, Shorter bones of ribs, pelvis and extremities, hands are broad and short,
show simian crease, fifth finger occurs inwards.
• GI: Esophageal or duodenal stenosis or atresia, imperforate anus and Hirschsprung disease
• Reproductive system: Men are sterile
• Immune system: Defective immunity
• Endocrine system: Antithyroid antibodies may cause hypothyroidism
• Hematologic disorders: Increased risk of Leukemia
• Neurologic disorders:
• Atlanto axial instability: characterized by excessive movement at the junction of the atlas(C1)
and axis (C2) vertebrae difficulty in walking, abnormal gait, restricted neck mobility, torticollis
etc.

45. Clinical Features