X-Linked Inheritance ✅

Question 1

What causes X-linked recessive disorders?

Answer 1

Mutations in genes on the X chromosome

Question 2

What is the result of the mutation being on the X-chromosome in X-linked recessive disorders?

Answer 2

It causes disease in males and leaves females unaffected or only mildly affected

Question 3

Where does the mutation come from in a boy affected by an X-linked recessive disorder?

Answer 3

Either inherited from mother or can occur de novo

Question 4

What is the % chance of a mother who is a carrier of an X-linked recessive disorder having an affected child?

Answer 4

25%

Question 5

Why is there a 25% chance of a mother who is a carrier of an X-linked recessive disorder having an affected child?

Answer 5

50% chance that she will pass on the affected chromosome, and 50% chance the offspring will be male

Question 6

What is the % chance a mother who is a carrier of an X-linked recessive disorder will have a carrier daughter?

Answer 6

25%

Question 7

What is the implication of having a de novo mutation causing an X-linked recessive disorder compared to inheriting the mutation from a carrier mother?

Answer 7

The risk of a further affected child is lower

Question 8

What is the usual risk of recurrence of a de novo mutation in a future child?

Answer 8

1%

Question 9

Why is the recurrence risk of de novo mutations in a future child higher than 1% for some X-linked recessive disorders?

Answer 9

Due to gonadal mosaicism

Question 10

Give an example of an X-linked recessive disorder where the recurrence risk of a de novo mutation in a future child is higher than 1%

Answer 10

Duchenne muscular dystrophy

Question 11

Can a man with a X-linked recessive disorder pass the condition on to his sons?

Answer 11

No

Question 12

Why can a man with an X-linked recessive disorder not pass the condition on to his son?

Answer 12

Because the man only passes on his Y chromosome

Question 13

What is the inheritance of Fragile X syndrome?

Answer 13

X-linked recessive

Question 14

What is the frequency of fragile X syndrome?

Answer 14

1 in 2000

Question 15

What causes Fragile X syndrome?

Answer 15

A triplet repeat expansion in the FMR1 gene

Question 16

Does fragile X syndrome show anticipation?

Answer 16

Yes

Question 17

What repeat length is ‘full mutation’ and causes disease in fragile X syndrome?

Answer 17

> 200

Question 18

What are repeat lengths of 55-200 known as in Fragile X syndrome?

Answer 18

‘Premutations’

Question 19

What is the clinical relevance of premutations in Fragile X syndrome?

Answer 19

Repeats can expand when transmitted to a child to become a full mutation

Question 20

What are the features of Fragile X syndrome?

Answer 20

• Moderate learning difficulties
• Relative macrocephaly
• Mitral valve prolapse

Question 21

Can females have Fragile X syndrome?

Answer 21

They can show features of the condition, but they are milder than males

Question 22

How is a diagnosis of Fragile X syndrome made?

Answer 22

Targeted genetic testing for expansion of the FMR1 gene

Question 23

What are X-linked dominant disorders caused by?

Answer 23

Mutations in genes on the X chromosome

Question 24

Are X-linked dominant disorders more common in females or males?

Answer 24

Females

Question 25

Why are X-linked dominant disorders more common in females?

Answer 25

Because the mutation is frequently lethal in males, often soon after conception

Question 26

How can X-linked dominant mutations be obtained?

Answer 26

• Inherited from affected mother

- De novo mutation

Question 27

What is the % chance of a woman with an X-linked dominant disorder passing it on to their daughter?

Answer 27

50%

Question 28

What is the risk that a surviving male is affected by an X-linked dominant disorder?

Answer 28

Very low (for most X-linked dominant disorders)

Question 29

What is the risk of recurrence in a future child of de novo mutations causing X-linked dominant disorders?

Answer 29

1%

Question 30

What does the 1% risk of recurrence in a future child of a de novo mutation causing an X-linked dominant disorder?

Answer 30

The small risk of gonadal moasacism

Question 31

What is the inheritance pattern of Rett syndrome?

Answer 31

X-linked dominant

Question 32

What is the incidence of Rett syndrome?

Answer 32

1 in 10,000-20,000 females

Question 33

What is Rett syndrome caused by?

Answer 33

A heterozygous loss-of-function mutation in the MECP2 gene

Question 34

Is the mutation in Rett syndrome inherited or de novo?

Answer 34

De novo

Question 35

What is the risk of recurrence of Rett syndrome in a future child?

Answer 35

1%

Question 36

What are the features of Rett syndrome?

Answer 36

Apparent normal early development followed by a period of regression and loss of language and motor skills, accompanied by deceleration of head growth at 6-18 months

Question 37

What stereotypical movements are seen in Rett syndrome?

Answer 37

Midline hand movements

Question 38

Are seizures common in Rett syndrome?

Answer 38

Yes

Question 39

How is Rett syndrome diagnosed?

Answer 39

Molecular genetic testing with sequencing and copy number analysis of the MECP2 gene