Non-cancer genetic disorders

Question 1

Describe the clinical presentation of Huntintons disease

Answer 1

• Onset 30-50 years
• Progressive chorea (involuntary movements) and psychiatric decline/dementia
• Prognosis is 17 years

Question 2

Describe the mechanism of inheritance of Huntingtons disease.

Answer 2

Autosomal dominant with genetic anticipation

• mutation of HTT gene with repeating CAG chain
• parental transmission expands the CAG chan
• longer chain = earlier onset

Question 3

Describe the pathogenesis of the repeating CAG chain in Huntingtons

Answer 3

• CAG codes for glutamine

- Aggregation of glutamine causes neurotoxicity

Question 4

Describe the clinical presentation of myotonic dystrophy

Answer 4

• Onset at 20
• Muscle dystrophy and myotonia
• Cataracts

Question 5

Describe the mechanism of inheritance of myotonic dystrophy

Answer 5

• repeating CTG chain
• expansion of chain via maternal transmission
• age of onset and severity with each generation

Question 6

What is the pathogenesis of Myotonic Dystrophy?

Answer 6

• Repeating CTG chain is non-coding, but interferes with the splicing of the DMPK gene
• Causes defective chlorine ion channel which causes symptoms

Question 7

What is the clinical presentation of cystic fibrosis?

Answer 7

• Recurrent respiratory infection
• Exocrine pancreas insufficiency
• Male infertility

Question 8

What id the mechanism of inheritance of cystic fibrosis?

Answer 8

Autosomal recessive - mutation to the CFTR gene

Question 9

What is the pathogenesis of cystic fibrosis?

Answer 9

• Mutation causes incorrect forlding and insertion into the cell membrane for the chloride channel
• Respiratory and pancreatic excretions are too thick

Question 10

What diagnostic testing/screening is available for CF?

Answer 10

• Neonatal screening then diagnostic DNA testing

- Cascade screening within the family of an affected individual

Question 11

What is cascade screening?

Answer 11

The family of an affected individual can be screened to see if they are carriers - must be of an age to give informed consent.

Question 12

What is the clinical presentation of neurofibromatosis type 1?

Answer 12

• Brown birth marks and neurofibromas (neural tumour which forms bumps on skin)
• Macrocephaly and learning difficulties

Question 13

What is the mechanism of inheritance of neurofibromatosis type 1?

Answer 13

Autosomal dominant

Question 14

What is the clinical presentation of Duchenne Muscular Dystrophy?

Answer 14

Progressive muscle dystrophy from 2/3

- Wheelchair by age 12

Question 15

What is the mechanism of inheritance of Duchenne muscular dystrophy?

Answer 15

X-linked recessive (affects boys)

Question 16

What the genetic pathophysiology of Duchenne Muscular Dystrophy?

Answer 16

Mutation to the DMD gene causes faulty dystrophin protein, causing weak and leaky muscle cells.
- High serum creatine kinase

Question 17

What is the clinical presentation of fragile X syndrome

Answer 17

• Intellectual disability

- Long face, large ears