Genomic medicine 1

Question 1

Type 1 Diabetes mode of inheritance

Answer 1

Polygenic

Other conditions: HTN, DM, Coronary heart disease, congenital hip dysplasia, asthma, schizophrenia, cleft palate

Question 2

Sickle cell disease mode of inheritance

Answer 2

Autosomal recessive
(inborn errors of metabolism)
Enzyme deficiency or metabolic disorders
Common autosomal recessive conditions:
Sickle cell, cystic fibrosis, Tay-sach, PKU, glycogen storage disease, muccopolysacchariodoses

Question 3

Leigh syndrome

Answer 3

Mitochondrial disease

Mitochondrial DNA is only maternal inherited

Question 4

Neurofibromatosis Type 1

Answer 4

Autosomal dominant
(NF-1&NF2, familial hyper cholesterolemia , Adult poly cystic kidney disease , Hereditary spherocytosis
Marfan’s
Huntington
BRCA 1/2 gene
Von Willibrand disease, HNPCC
Peutz-Jegher’s syndrome (multiple polyps in GIT and muco cutaneous pigmentation)

Question 5

Indian origin, white hairs and skin, pale pink eyes

Answer 5

Occulo-cutaneous albenism
(not making any melanin-as no active tyrosinase)
Affected gene on chromosome 11
At risk of:
Poor visual acuity, Nystagmus
Meets criteria of blind child
Skin cancers( Malignant melanoma, squamous cell carcinoma, basal cell carcinoma)
Social difficulties due to being looking different

Question 6

Risk of cystic fibrosis in baby born to healthy parents but brother with CF

Answer 6

25% risk (as autosomal recessive)

25% healthy
50% carriers
Effects males and females equally

Question 7

Low set ears, small eyes, micrognathia, cleft lip and palate, microcephalic face and prominent occipital bone

Answer 7

Edward syndrome (Trisomy Eighteen)

Patau syndrome similar presentation but broad flat nose and sloping forehead

Question 8

Primary amenorrhea, short for age, broad chest, widely spaced nipples

Answer 8

Turner’s syndrome (45XO) 
Gonadal hypoplasia, failure of growth spurts.
Also webbed neck.
Normal IQ 
HTN due to coarctation of Aorta

Question 9

Gynecomastia, small firm testes, infertility, tall and skinny

Answer 9

Klinefelter’s syndrome (47XXY)

Question 10

1 year old, not standing independently, not speaking any words, only babble, does not interact and appears slow
O/E: Strabismus, joint extension

Answer 10

Fragile X.
FMR-1 gene mutation
Large head, global developmental delay, autism like feature with hyperactivity
Low IQ, Prominent forehead and large jaw.

Question 11

Screen risk for Down’s syndrome

Answer 11

1:1500 @20years of age
1:800 @30 years of age
1:270 @35 years of age
1:100 @40 years of age
>1:50 above 45 years of age

If risk is over 1:150 , diagnostic test is offered

Question 12

Diagnostic tests for Down’s syndrome

Answer 12

Chorionic villus sampling- Performed before 13 weeks of gestation

Amniocentesis- performed after 15weeks of gestation

If risk is over 1:150 , diagnostic test is offered

Question 13

Mother carrier, father status unknown

Risk of Cystic fibrosis in child

Answer 13

Do prenatal screening.

Antenatal genetic testing

Question 14

To detect genetic changes in embryo created using IVF

Answer 14

Pre-implantation testing

Question 15

Medial Epicanthic folds, low set ears, flat nasal bridge

Answer 15

Down’s syndrome

Question 16

Predictive testing

Answer 16

To detect genetic mutations that appear after birth and often later in life (e.g Hemochromastosis/ BRCA gene)

Question 17

Brush field spots

Answer 17

Grey spots on iris - Seen in Down’s syndrome

Question 18

Screening tests for Down’s syndrome

Answer 18

Combination of US and two bloods tests

US performed between 11-14 weeks for nucchal translucency
Beta-hCG and PAPP-A (Pregnancy associated plasma protein A) levels

Question 19

Down’s syndrome screening after 16weeks

Answer 19

Combination of 4 blood tests /Quadruple test

Question 20

NICE guidance for gestational diabetes

Answer 20

OGTT at booking for high risk patients:
BMI>30
Previous macrosomic baby (>4.5kg) 
Previously GDM
1st degree relative with DM
Family origin with high prevalence of DM (South Asian, Black Caribbean, Middle Eastern)