Genetics

Question 1

Down Syndrome genetics

Answer 1

Trisomy 21

Question 2

Clinical features of down syndrome

Answer 2

Hypotonic
Flat occiput
Single palmar crease
Wide sandal gap between 1st and 2nd toe
Flat nasal bridge
Brushfield spots in iris
Epicanthic folds
Small ears and small mouth
Upslanted palpebral fissure
Duodenal atresia
Congenital heart defect esp AVSD
Delayed motor milestones
Learning difficulties
Alzheimer's disease

Question 3

Possible genetic mutations for trisomy 21 to occur

Answer 3

Meiotic non-disjunction (most common), translocation (Robertsonian) or mosaicism

Question 4

Genetics of Edwards syndrome

Answer 4

Trisomy 18

Question 5

Clinical features of Edwards syndrome

Answer 5

LBW
Prominent occiput
Small mouth
Short sternum
Rocker-bottom feet
Over-lapping flexed fingers

Question 6

Genetics of Patau syndrome

Answer 6

Trisomy 13

Question 7

Clinical features of Patau syndrome

Answer 7

Scalp and cerebral defects
Small eyes
Cleft lip and palate
Polydactyly
Patent ductus arteriosus

Question 8

Turner’s syndrome genetics

Answer 8

45, X (loss of an X chromosome). Females only!
Short statue
Coarctation of aorta
Lymphoedema of hands and feet.
Web neck
Widely spaced nipples
Hearing loss and recurrent otitis media
Behaviour problems
Amenorrhoea and impaired/delayed puberty
Gonadal dysgenesis.

Question 9

Management of Turner’s

Answer 9

Growth hormone

At puberty = oestrogen replacement.

Question 10

Klinefelter’s syndrome genetics

Answer 10

XXY

Question 11

Clinical features of Klinefelter’s

Answer 11

Males only.
Hypogonadism
Infertility
Gynaecomastia
Tall stature
Psychological issues

Question 12

Management of Klinefelter’s

Answer 12

Androgen therapy

Question 13

Genetics of fragile X and another name

Answer 13

Martin-Bell syndrome
FMR1 gene has lengthen and pathologically repeated CGG repeat (over 200x), absent fragile X protein.
X-linked

Question 14

Carriers of fragile X

Answer 14

Pre-mutation of under 200x CGG repeats. All patient os Fragile X will have a carrier mother.

Question 15

Clinical features of fragile X

Answer 15

Macrocephaly = long narrow face, large ears, prominent jaw.
Delayed motor, speech and language milestones and development.
Hyperactivity
Mood swings
Autism
Learning difficulties
large testes post-pubertal.

Question 16

Management of fragile X

Answer 16

Minocycline improves behaviour.

Question 17

Noonan’s syndrome

Answer 17

Autosomal dominant. Mutation in the RAS-MAPK pathway.
Short stature
Ptosis, downward slanting eyes, low set ears.
Congenital heart defect - pulmonary stenosis
Web neck
Spine and check deformity.
Learning difficulties

Question 18

William’s syndrome

Answer 18

Autosomal dominant
Infantile hypercalcaemia
Short stature
Congenital heart defects - aortic stenosis
Broad forehead
Strabismus
Wide mouth
Learning difficulties.

Question 19

Prader-Willi genetics

Answer 19

Loss of paternal contributed long arm of chromosome 15

Question 20

Clinical features of prader-willi

Answer 20

Infant = hypotonia, poor feeding, hypoplasia of genitals.
Child = hyrerphagia, obesity, short stature, behavioural problems.

Question 21

Becker’s muscular dystrophy

Answer 21

X linked.
Semifunctional dystrophin.
Milder symptoms to Duchenne MD and later onset.
Increased creatinine kinase

Question 22

Duchenne Muscular dystrophy

Answer 22

X linked
Loss of dystrophin
Waddling, clumsy gait
Hypertrophy of calves
Gower's manoever to stand using hands
HIGH creatinine kinase
Dx with muscle biopsy.
Rx prednisolone

Question 23

Angelmans syndrome

Answer 23

Unprovoked laughing and clapping
Microcephaly
Seizures
Ataxia
Broad based gait
Mental retardation

Question 24

Genetics of Angelmans syndrome

Answer 24

Maternal deletion of chromosome 15.