Genetic Disorders

Question 1

Triplet repeat disorders can demonstrate ____.

Answer 1

Anticipation; meaning that there may be progressively earlier onset and increased severity over successive generations - this is because the # of triplet repeats increases with each generation

Question 2

Mitochondrial DNA mutations are passed down from which parent?

Answer 2

The mother

Question 3

What generational features are commonly seen in autosomal recessive diseases?

Answer 3

• Usually see the condition in one generation
• Both parents are carriers
• Increased risk with consanguinity

Question 4

What generational features are commonly seen in autosomal dominant diseases?

Answer 4

• Condition often seen in multiple generations
• Often one of the parents is affected
• Exceptions may be in cases of reduced penetrance or late-onset of disease

Question 5

What generational features are commonly seen in X-linked recessive diseases?

Answer 5

• The incidence is much higher in males than in females
• Heterozygous females are usually unaffected but may display disease depending on pattern of X inactivation
• The mutant allele is transmitted by the affected male to all his daughters
• Females are often carriers
• Any of his daughters’ sons have a 50% chance of inheriting the gene

Question 6

What generational features are commonly seen in X-linked dominant diseases?

Answer 6

• Females are more frequently affected because all daughters of an affected man will be affected too
• Can have affected males and females if the mother is affected

Question 7

When is testing family members of a proband useful, apart from when there is a positive result?

Answer 7

Genetically testing family members for a VUS present in the probrand can tell us whether the VUS has a high chance of being pathologic (ex. the presence of a VUS in family members with a similar condition as the proband would make us highly suspicious, AND the lack of the VUS in unaffected parents would also make us suspicious)

Question 8

What is a syndrome?

Answer 8

Well-characterized constellation of major and minor anomalies that occur together in a predictable fashion presumably due to a single underlying etiology (ex. Down syndrome)

Question 9

Why do we counsel a 1% risk of recurrence for de novo genetic conditions?

Answer 9

• Gonadal mosaicism - genetic change is only present in the gonads but not detectable in the blood

Question 10

What is the chance of passing down an autosomal recessive disorder?

Answer 10

25% chance IF both parents are confirmed carriers (12.5% if only one is a confirmed carrier)

Question 11

What generational features are commonly seen in mitochondrial DNA diseases?

Answer 11

No male-to-male transmission

Question 12

What is locus heterogeneity?

Answer 12

One syndrome with many possible causative genes

Question 13

When should a monogenic disease be suspected?

Answer 13

• When there are facial differences
• When there is a suspicious family history
• When there are developmental challenges
• When there is a major anomaly or multiple minor anomalies
• When there are several unexplained diagnoses in one individual
• When the patient is younger than expected for a condition
• When the patient lacks risk factors for a condition