Inheritance

Question 1

Cystic Fibrosis - what is the inheritance?

Answer 1

Autosomal recessive

Question 2

Cystic Fibrosis- what are the key characteristics?

Answer 2

Autosomal recessive, mutation in the CTFR (cystic fibrosis transmembrane conductance regulator) gene on chromsome 7, the most common mutation is deletion of F508 (delta F508 mutation in 70% of cases) - excess mucus production and chloride in sweat - recurrent chest infections, poor gas exchange, pancreatitis, cirrhosis, intestinal obstruction, malabsorption of fat soluble ADEK vits, osteoporosis, diabetes, Infertility

Question 3

Why does CF lead to infertility?

Answer 3

Absent vas deferens (men), thickened cervical mucus (women)

Question 4

Fragile X syndrome - what is the inheritance?

Answer 4

X-linked dominant (but features less prominent in females, some texts refer to the condition as recessive)

Question 5

Fragile X syndrome - what are the characteristics?

Answer 5

FMR1 mutation, X-linked dominant inheritance but phenotype suppressed in females so some texts refer to as recessive- long face, protruding ears, enlarged testes(macroorchidism), low muscle tone, flat feet, learning difficulties, may have autism adhd, seizures

Question 6

Duchenne’s Muscular Dystrophy - what is the inheritance?

Answer 6

X-linked recessive

Question 7

Duchenne’s Muscular Dystrophy - what are the characteristics?

Answer 7

X-linked recessive inheritance, progressive neuromuscular disorder, weakness and wasting affecting the hip and shoulder girdle first. Mutation of the dystrophin Xp21 gene

Question 8

What are the features of X-linked recessive inheritance?

Answer 8

Only males are affected, females can be carriers, fathers can not pass the recessive gene onto sons, only mothers can transfer the gene. Knight’s move pattern of inheritance = any male grandchild of an affected male

Question 9

Turner syndrome- what is the inheritance?

Answer 9

Chromosomal abnormality (sex chromosome aneuploidy) - 45 X0

Question 10

Turner Syndrome - what are the characteristics

Answer 10

Sex chromosome aneuploids 45X0 (monosomy X), typically caused by loss of a Barr body - raised nuchal translucency, neck webbing, cystic hygroma, short stature, wide carrying arm angle, shield shaped chest, normal intelligence, infertility and prevention of developing female sex characteristics due to gonadal dysgenesis (loss of germ cells on developing embryo), horshoe kidney, cardiac abnormalities, 1 in 2500 live births but 90% will miscarry before term

Question 11

Christmas disease - what is the inheritance?

Answer 11

X-linked recessive inheritance

Question 12

Christmas disease - what are the characteristics?

Answer 12

X-linked recessive inheritance, factor XI deficiency haemophilia B (second most common haemophilia)

Question 13

Prader-Willi syndrome - what is the inheritance?

Answer 13

Chromosomal microdeletion

Question 14

Prader-Willi syndrome - what are the characteristics?

Answer 14

Chromosomal microdelition, chromosome 15, obesity, type 2 diabetes, may have learning difficulties, lack of sexual development, due to gene deletion (paternally deleted genes and maternal imprinting)

Question 15

What is chromosomal microdeletion?

Answer 15

A genetic abnormality caused by deletion of a small sub-set of genes located near to each other on a chromosome accounting for the deletion of less than 5 million base pairs

Question 16

Angelman syndrome - what is the inheritance?

Answer 16

In many cases it is caused by chromosomal microdeletion (maternal gene deletion rather than paternal gene deletion seen in Prader-Willi syndrome)

Question 17

Cri-du-chat syndrome - what is the inheritance?

Answer 17

Chromosomal microdeletion on short arm of chromosome 5

Question 18

Angelman syndrome - what are the characteristics?

Answer 18

Predominately caused by a chromosomal microdeletion on the maternal gene with paternal imprinting - results in a neurodevelopmental disorder, severe developmental delay, happy demeanor, elf-like features

Question 19

Cri-du-chat syndrome

Answer 19

Chromosomal microdeletion on chromosome 5 (short arm), developmental delay, small head and jaw, characteristic cry

Question 20

When is nuchal translucency measured?

Answer 20

Between 11-14 weeks

Question 21

What conditions are associated with increased nuchal translucency?

Answer 21

Down’s syndrome, Patau syndrome, Edward’s syndrome, Turner syndrome, Noonan syndrome, major cardiac abndomalities

Question 22

Noonan syndrome - what is the inheritance?

Answer 22

Autosomal dominant

Question 23

Noonan syndrome - what are the characteristics?

Answer 23

Autosomal dominant inheritance (most commonly), several different genes with KRAS gene mutation being the most common, clinical features include short stature, congenital heart defects, wide brow, neck webbing, low set ears

Question 24

What is the most common cause of trisomy?

Answer 24

Non-disjunction during meiosis 1

Question 25

What is the most common trisomy to result in miscarriage?

Answer 25

Trisomy 16

Question 26

What is the most common trisomy compatible with life?

Answer 26

Trisomy 21

Question 27

Kleinfelter’s syndrome - mode of inheritance

Answer 27

Sex chromsome aneuplody 47XXY

Question 28

Kleinfelter’s syndrome- what are the characteristics?

Answer 28

Tall, small testes (hypogonadotrophic hypogonadism), infertility

Question 29

Red-green colour blindness - mode of inheritance

Answer 29

X-linked recessive

Question 30

Infantile polycystic kidney disease - what is the mode of inheritance and what are the characteristics

Answer 30

Autosomal recessive inheritance, enlarged polycystic kidneys, reduced amniotic fluid, underdeveloped lungs, underdeveloped liver, internal bleeding, reduced life expectancy (most will dies in infancy)

Question 31

Osteogenesis imperfecta - mode of inheritance

Answer 31

Autosomal dominant

Question 32

Osteogenesis imperfecta - what are the characteristics?

Answer 32

autosomal dominant inheritance, blue sclera, brittle bones that break easily, multiple different types but most common mutation on COL1A1

Question 33

Beta Thalassaemia - mode of inheritance

Answer 33

Autosomal recessive

Question 34

Which gene is affected in fragile x syndrome?

Answer 34

FMR1 gene on the X chromosome which codes for FMRP protein, important for building synapses in the brain. In normal fmr1 genes there is a cgg repeat 5 to 40 times but when mutated in fragile X it is repeated over 200 times making the gene unable to produce the FMRP protein

Question 35

Congenital adrenal hyperplasia - what is the inheritance?

Answer 35

autosomal recessive

Question 36

Congenital adrenal hyperplasia - what is the most common gene/protein affected?

Answer 36

CYP21A gene - 21-hydroxylase (resulting in androgen excess and mineralcorticoid deficiency)

Question 37

Phenylketonuria - inheritance

Answer 37

autosomal recessive

Question 38

Test for PKU

Answer 38

guthrie (heel prick test) done after 12 hours of birth, usually within 5 days

Question 39

Consequences of PKU

Answer 39

error in amino acid metabolism - severe deficiency in phenylalanine hydroxalase and therefore cannot metabolism phenylalanie resulting in a build of phenylpyruvic acid and phenylethylamine, which become neurotoxic in high concentrations. Untreated, this can result in learning difficulties and seizures