GENETICS FOR THE MRCOG PART 1

1. 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. 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). 15. AD deafness. 16.
osteogenesis imperfecta. 17. Noonans syndrome. 18. myotonic dystrophy. 19.
Tuberous sclerosis. 20. Ehler danlos syndrome. 21. heridetry hemorrhagic telagectasia
(AKA oslerweber-rendau disease).

2. AUTOSOMAL RECESSIVE

1. Cystic fibrosis 2. Sickle cell disease 3. thalasemia 4. phenylketonuria (PKU) 5.

Congenital adrenal hyperplasia 6. wilsons disease. 7. Glycogen storage diseases. 8.
Tay sachs disease (AKA hexoaminidase A) 9. Gauchers disease. 10. homocystenuria
11. ataxia telangectasia 12. ARPKD (infantile PKD) 13. Albinism 14.
hemochromatosis 15. mucopolysacridosis (except hunters disease) 16.
sphingolipidosis (except Fabrys disease) 17. Usher syndrome 18. fredrich ataxia 19.
spinal muscle atrophy 20. kartagners syndrome 21. wolframs syndrome

3. 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, male and female offspring are equally affected

examples: 1. Fragiles X Syndrome. [CGG] 2. Rett syndrome. 3. hypophosphatemic

rickets (perviously vitamin D resistant rickets) 4. incontinentia pigmenti. 5. Xg blood
group.

4. codominanace inheritance neither of the two allele are dominant

5. 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 7. Alport syndrome 8. wiskott aldrich syndrome 9.
hunters syndrome 10. menkes disease 11. fabrys disease 12. nephrogenic
diabetes insipidus

6. MITOCHONDRIAL INHERITANCE
1. mitochondrial myopathies 2. Lebers hereditary optic neuropathy. 3. Leighs
syndrome
7. TRINUCLEOTIDE REPEATS Disease Repeat
1. huntington disease CAG
2. fragile X syndrome CGG
3. Myotonic dystrophy CTG
4. friedreich ataxia GAA
8. 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)
GAIN of chromosomes
1. 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

DOWN SYNDROME 1. increase risk for : alzheimer disease AML/ALL

hypothyroidism 2. raised nuchal translucency

2. EDWARD SYNDROME Trisomy 18

1. increase nuchal translucency
2. musculoskeletal defect
3. facial defects
4. cardiac defects abdominal defects
5. mortality rate
1. 1 month = 30%
2. 2 month = 50%
3. 1 year = 90%
6. IUGR
7. male : female 1:2
8. UK prevalence 1:3000 live birth
3. PATAUS SYNDROME trisomy 13
1. midline defects incidence increase with maternal age
2. post axial polydactyly
3. congenital heart defect
4. renal abnormality
5. omphalocele
6. IUGR UK prevalence 1:5000 live births
7. mortality rate 100% by 1 month age.
4. KLIENFILTER SYNDROME 47, XXY
1. incidence 1:1000 live birth
5. TURNER SYNDROME 45,X or 45,XO
1. intellectually normal risk for gonadoblastoma

9. DELETION
 1. microdeletion syndrome and chromosome affected
1. cri-du-chat 5
2. williams 7
3. angleman 15
4. prader-willi 15
5. smith magenis 17
6. Di-George 22
10. 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

11. IMPRINTING example

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

12. MULTIFACTORIAL INHERITANCE

1. HTN DM PreEclampsia CDH major NTD congenital heart disease cleft
lip & palate. Atopy
2. Tuberculosis, Scurvy, Peptic ulcer, Diabetes
1. Common
2. Genetics complex
3. Multifactorial
4. Low recurrence rate
3. Phenylketonuria, Galactosaemia Spina bifida Ischaemic heart disease
Ankylosing spondylitis Club foot Pyloric stenosis Dislocation of hip
Duchenne muscular dystrophy Haemophilia Osteogenesis imperfecta
1. Rare
2. Genetics simple
3. Unifactorial
4. High recurrence rate
13. INVESTIGATIONS
1. Karyotyping (chromosomal analysis)
2. FISH (molecular cytogenetics)

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