1. GENETICS FOR THE
MRCOG PART 1
YAZID JIBREL
ROYAL MEDICAL SERVICES

2. •
Clinical genetics is a speciality concerned with
the investigating and diagnosis of patients of all
ages with disorders that may be inherited

5. AUTOSOMAL DOMINANT
1. Achondroplasia
2. Huntigton disease
3. Von willbrand disease
4. heridetry spherocytosis
5. marfan syndrome
6. neurofibromatosis type 1 and 2
7. retinoblastoma

6. AUTOSOMAL DOMINANT
1. Achondroplasia
2. Huntigton disease
3. Von willbrand disease
4. heridetry spherocytosis
5. marfan syndrome
6. neurofibromatosis type 1 and 2
7. retinoblastoma

7. AUTOSOMAL DOMINANT
1. Achondroplasia
2. Huntigton disease [CAG]
3. Von willbrand disease
4. heridetry spherocytosis
5. marfan syndrome
6. neurofibromatosis type 1 and 2
7. retinoblastoma

8. AUTOSOMAL DOMINANT
1. Achondroplasia
2. Huntigton disease
3. Von willbrand disease
4. heridetry spherocytosis
5. marfan syndrome
6. neurofibromatosis type 1 and 2
7. retinoblastoma

9. AUTOSOMAL DOMINANT
8. von hippel lendeau disease.
9. Adult polycystic kidney disease
10. breast cancer.
11. acute intermittent porpheryia.
12. MEN
13. familial hypercholestrolemia
14. familial polyposis coli (AKA familial adenomatous
polyposis).

10. AUTOSOMAL DOMINANT
8. von hippel lendeau disease.
9. Adult polycystic kidney disease
10. breast cancer.
11. acute intermittent porpheryia.
12. MEN
13. familial hypercholestrolemia
14. familial polyposis coli (AKA familial adenomatous
polyposis).

11. AUTOSOMAL DOMINANT
8. von hippel lendeau disease.
9. Adult polycystic kidney disease
10. breast cancer.
11. acute intermittent porpheryia.
12. MEN
13. familial hypercholestrolemia
14. familial polyposis coli (AKA familial adenomatous
polyposis).

12. AUTOSOMAL DOMINANT
15. AD deafness.
16. osteogenesis imperfecta.
17. Noonan’s syndrome.
18. myotonic dystrophy.
19. Tuberous sclerosis.
20. Ehler danlos syndrome.
21. heridetry hemorrhagic telagectasia (AKA oslerweber-rendau disease).

13. AUTOSOMAL RECESSIVE
1. Cystic fibrosis
2. Sickle cell disease
3. thalasemia
4. phenylketonuria (PKU)
5. Congenital adrenal hyperplasia
6. wilson’s disease.
7. Glycogen storage diseases.

14. AUTOSOMAL RECESSIVE
1. Cystic fibrosis
2. Sickle cell disease
3. thalasemia
4. phenylketonuria (PKU)
5. Congenital adrenal hyperplasia
6. wilson’s disease.
7. Glycogen storage diseases.

15. AUTOSOMAL RECESSIVE
1. Cystic fibrosis
2. Sickle cell disease
3. thalasemia
4. phenylketonuria (PKU)
5. Congenital adrenal hyperplasia
6. wilson’s disease.
7. Glycogen storage diseases.

16. AUTOSOMAL RECESSIVE
8. Tay sachs disease (AKA hexoaminidase A)
9. Gauchers disease.
10. homocystenuria
11. ataxia telangectasia
12. ARPKD (infantile PKD)
13. Albinism
14. hemochromatosis

17. AUTOSOMAL RECESSIVE
15. mucopolysacridosis (except hunter’s disease)
16. sphingolipidosis (except Fabry’s disease)
17. Usher syndrome
18. fredrich ataxia
19. spinal muscle atrophy
20. kartagner’s syndrome
21. wolfram’s syndrome

18. X-LINKED DOMINANT
•
we have 2 scenarios of inheritance:
1. the affected father
2. the affected mother
•
dominant = every generation (no skip
generation)
•
X-liked = no male to male transmission

19. X-LINKED DOMINANT
•
dominant = every generation (no skip generation)
•
X-liked = no male to male transmission
•
male and female offspring are equally affected

20. X-LINKED DOMINANT
•
examples:
1. Fragiles X Syndrome. [CGG]
2. Rett syndrome.
3. hypophosphatemic rickets (perviously vitamin D resistant
rickets)
4. incontinentia pigmenti.
5. Xg blood group.

21. codominanace inheritance
neither of the two allele are
dominant

22. X-LINKED RECESSIVE
1. Duchhennes muscular dystrophy
2. red green color blindness
3. G6PD
4. hemophilia (A, B, and C)
5. lesch-Nyhan syndrome (AKA HGPRT
deficiency)
6. ichthyosis

23. X-LINKED RECESSIVE
7. Alport syndrome
8. wiskott aldrich syndrome
9. hunter’s syndrome
10. menke’s disease
11. fabry’s disease
12. nephrogenic diabetes insipidus

24. MITOCHONDRIAL
INHERITANCE
1. mitochondrial myopathies
2. Leber’s hereditary optic neuropathy.
3. Leigh’s syndrome

25. TRINUCLEOTIDE REPEATS
Disease
Repeat
huntington disease
CAG
fragile X syndrome
CGG
Myotonic dystrophy
CTG
friedreich ataxia
GAA

27. ANEUPLOIDY
•
Aneuploidy, a deviation from the eupliod number,
represents the gain (+) or loss (-) of a specific
chromosome.
•
two major aneuploidies are observed:
1. monosomy (loss of chromosome).
2. trisomy (gain of chromosome)

28. DOWN SYNDROME
•
•
Trisomy 21
•
prevalance 1:700 live births
•
due to :
1. 1ry trisomy (nondysjunction) 95%
2. robertsonian translocation of
chromosome 14 : 21 (3%).
3. mosaicism (1%)
maternal age risk for down syndrome
1. 25 years old = 1 : 1500
2. 30 years old = 1: 900
3. 35 years old = 1:350
4. 40 years old = 1: 100
5. 45 years old = 1:30
6. 50 years old = 1:11
7. cut off for invasive screen 1:250

29. DOWN SYNDROME
1. increase risk for :
alzheimer disease
AML/ALL
hypothyroidism
2. raised nuchal translucency

30. EDWARD SYNDROME
•
Trisomy 18
•
increase nuchal translucency
•
musculoskeletal defect
•
facial defects
•
cardiac defects
1. 1 month = 30%
•
abdominal defects
2. 2 month = 50%
•
IUGR
•
•
•
male : female 1:2
UK prevalence 1:3000 live
birth
mortality rate:
3. 1 year = 90%

31. PATAU’S SYNDROME
•
•
•
•
trisomy 13
•
midline defects
incidence increase with
maternal age
•
post axial polydactyly
•
congenital heart defect
•
renal abnormality
•
omphalocele
•
IUGR
UK prevalence 1:5000 live
births
mortality rate 100% by 1
month age.

32. KLIENFILTER SYNDROME
•
47, XXY
•
incidence 1:1000 live birth

33. TURNER SYNDROME
•
45,X or 45,XO
•
intellectually normal
•
risk for gonadoblastoma

34. DELETION
microdeletion syndrome
chromosome affected
cri-du-chat
5
williams
7
angleman
15
prader-willi
15
smith magenis
17
Di-George
22

35. TRANSLOCATION
•
the exchange of 2 segments of chromosome between nonhomologous chromosomes
•
2 types:
1. balanced: an even exchange of material with no excess or loss
2. unbalanced: unequal exchange in genetic material
•
Robetsonian translocation result from fusion of the long arms
of 2 acrocentric chromosomes

36. TRANSLOCATION

37. TRANSLOCATION

38. IMPRINTING
•
Angelman 15q11-13
•
maternal deletion
1. happy disposition
2. macroglossia
3. ataxia
4. seizures
5. learning difficulty
•
Prader-Willi 15q11-13
•
paternal deletion
1. obese
2. hypogonadism
3. hypotonia

40. MULTIFACTORIAL
INHERITANCE
GENETIC
Tuberculosis
ENVIRONMENTAL
Phenylketonuria
Galactosaemia
Rare
Genetics simple
Unifactorial
High recurrence rate
Spina bifida
Ischaemic heart disease
Ankylosing spondylitis
Common
Genetics complex
Multifactorial
Low recurrence rate
•
DM
PreEclampsia
•
Club foot
Pyloric stenosis
Dislocation of hip
Duchenne
muscular dystrophy
Peptic ulcer
Diabetes
HTN
•
Haemophilia
Osteogenesis imperfecta
•
major NTD
•
congenital heart disease
•
cleft lip & palate.
•
Atopy
•
CDH
Scurvy

42. INVESTIGATIONS
•
Karyotyping (chromosomal analysis)
•
FISH (molecular cytogenetics)

43. GENETICS LINGO
•
There is an agreed format for the describing chromosomal
abnormalities and this forms the basis of reports from
cytogenitic laboratory.
•
example: 46,XY,t(2;3)(p21;q29)
•
translocation: t
•
deletions: der
•
duplication: dup

44. THANK YOU