Genetics

Question 1

What is Wilson’s Disease? What are the complications?

Answer 1

Build up/deposition of copper throughout the body
- psychiatric disorders
- hepatomegaly
- kayser-fleischer ring
- cardiomyopathy
- movement disorders (myoclonus)
- renal tubular dysfunction
- arthritis
- CNS disorders
Mutation in the ATP7B gene (autossomal recessive)

Question 2

What mutation is associated with Wilson’s disease? What can be used other than this to diagnose?

Answer 2

Mutation in the ATP7B gene (autosomal recessive).
Low ceruloplasmin level.

Question 3

Is serum copper low or high in Wilson’s Disease? Why?

Answer 3

Low due to deposition within the organs.

Question 4

How is Wilson’s Disease managed? What are the side effects of this medication?

Answer 4

Penicillamine- chelates copper to reduce build up.
Can cause nephrotic syndrome, drug induced SLE, and myasthenia-gravis.

Question 5

What is the karyotype for Turner’s syndrome?

Answer 5

45XO

Question 6

What cardiac defects are associated with Turner’s syndrome?

Answer 6

Bicuspid aortic valve and coarctation of the aorta

Question 7

What are the features of Down’s Syndrome?

Answer 7

congenital heart and neural defects along with changes to the physical appearance, such as a flat occiput, upslanting palpebral fissures and small, low-set ears.

Question 8

What is a +ve test in the 15 week screening for Down’s?

Answer 8

Low AFP, low uE3, high bHCG

Question 9

What causes myotonic dystrophy type 1?

Answer 9

Trinucleotide repeat disorder of DMPK gene - autosomal dominant

Question 10

What are the clinical features of myotonic dystrophy type 1?

Answer 10

• Face: frontal balding, bilateral ptosis, long and thin face, cataracts
• Speech: dysarthria
• Neck: SCLM wasting
• Hands: percussion myotonia, distal wasting, slow reflex grip
• Internal features: testicular trophy, metabolic syndromes and insulin resistance, arrhythmias, cardiomyopathies

Question 11

What causes Friedrich’s Ataxia? What is the usual age of onset?

Answer 11

Trinucleotide repeat disorder.
10-15 y/o.

Question 12

What are the clinical signs of Friedrich’s ataxia?

Answer 12

• Neurological signs: ataxia, dysarthria, lower limb weakness, upgoing plantares, sensory impairments
• External signs: muscle wasting, kyphoscoliosis, high arched palate
• Internal: HOCM (systolic murmur), reduced visual acuity, T1DM, deafness

Question 13

Edward’s Syndrome is a trisomy of which chromosome? What are the clinical features?

Answer 13

Trisomy 18, heart defects (VSD), oesophageal atresia, omphalocele, microcephaly, low set ears, overlapping digits.

Question 14

Patau’s Syndrome is a trisomy of which chromosome? What are the clinical features?

Answer 14

Trisomy 13,cleft palate, microcephaly, intelectual disability, polydactyly.

Question 15

What is Noonan’s Syndrome caused by? What are the clinical features?

Answer 15

Mutation in PTPN11, SOS1, and RIT1 gene mutations are all attributable,
Most common is PTPN11 (50%).
Pulmonary stenosis, short stature and a webbed neck.

Question 16

What mutation causes Marfan’s Syndrome?
What is the inheritance pattern?

Answer 16

Fibrillin-1 mutation on chromosome 15q21.
Autosomal dominant.

Question 17

What chromosome is affected in Prader-Willi Syndrome?

Answer 17

Loss of function of genes of the paternal copy of chromosome 15.

Question 18

What are the signs of Marfan’s Syndrome?

Answer 18

• Tall and thing with unusually long limbs
• Arachnodactyly
• High-arched palate
• Cardiovascular cx
• Ophthalmic cx
• MSK abnormalities
• Neurological abnormalities

Question 19

What are the signs/symptoms of Prader-Willi Syndrome?

Answer 19

• Poor feeding in infancy
• Hyperphagia in later childhood
• Morbid obesity
• Hypotonia
• Short stature
• Developmental delay
• Skin picking which results in cellulitis

Question 20

What causes fragile X syndrome?

Answer 20

CGG trinucleotide repeat on FMR1 gene on X chromosome.

Question 21

What are the manifestations of fragile X syndrome?

Answer 21

• Intellectual disability
• Anxiety
• Autistic features
• Long face
• Protruding ears
• Hypermobile joints
• post-pubertal macroorchidism (large testes).