Commoner (Non-Cancer) Genetic Disorders

Question 1

What are the clinical aspects of Huntington disease?

Answer 1

• Onset 30-50 years
• AD with genetic anticipation
  Triplet repeat (unstable length mutation of HTT gene)

Question 2

What are the clinical aspects of myotonic dystrophy?

Answer 2

• Progressive muscle weakness, myotonia, cataracts, diabetes and cardiac problems
• AD with genetic anticipation
• Unstable length mutation of CTG repeat (affected if 50 or more)

Question 3

What are the clinical aspects of CF?

Answer 3

• Recurrent lung infection, bronchiectasis and obstructive lung disease
• AR
• Diagnosed by IRT level
• CTFR mutations (F508del most common) lead to defective chloride channel so increased thickness of secretions

Question 4

What are the clinical aspects of NF-1?

Answer 4

• Cafe au lait macules, neurofibromas, short stature, macrocephaly, learning difficulties, lisch nodules, scoliosis and tibial fractures
• AD
• Mutations cause truncation of the protein neurofibromin (prevents activity of ras signalling) and so increased ras activity

Question 5

What are the clinical aspects of DMD?

Answer 5

• Progressive proximal muscle weakness (usually before age of 5 - delayed walking), contractures, raised CK, respiratory failure, cardiomyopathy, scoliosis and learning disability
• X-LR
• Knight’s move pattern
• DMD gene (Xp21) encodes for dystrophin protein which allows muscles to exert their contraction - not present in DMD

Question 6

What are the clinical aspects of fragile X syndrome?

Answer 6

• Learning difficulties
• X-LR with genetic anticipation
• Abnormality in FMR1 gene resulting in loss of the protein FMRP, necessary for normal development of neuronal dendritic spines and synapses required for learning and memory

Question 7

What are the clinical aspects of Down syndrome?

Answer 7

• Learning difficulties, and risk of heart malformations

- Trisomy 21

Question 8

What are the clinical aspects of Edwards syndrome?

Answer 8

• Learning difficulties, small chin, clenched hands with overlapping fingers, malformations of heart, kidney and other organs
• Trisomy 18

Question 9

What are the clinical aspects of Patau syndrome?

Answer 9

• Congenital heart disease, left lip and palate, microphthalmia, abnormal ears, clenched fists and post axial polydactyly
• 50% die within 1 month
• Trisomy 13