X-linked Dominant Disorders

Question 1

What is the mnemonic for X-linked dominant disorders?

Answer 1

FAIR

Question 2

What are the X-linked dominant disorders?

Answer 2

F = Familial hypophosphataemic rickets (vitamin D resistant rickets)

Fragile X syndrome (complex X linked)

A = Alport syndrome (in 85% cases; 10-15% are autosomal recessive)

I = Incontinentia pigmenti

R = Rett’s syndrome

peRiventriculaR nodulaR heteRoptia

Question 3

Which X-linked dominant disease is a complex X-linked?

Answer 3

Fragile X syndrome

Question 4

What is the inheritence pattern Alport syndrome?

Answer 4

>80% is X-linked dominant

Few cases are ADAS (Autosomal Dominant Alport Syndrome)

Question 5

How many mutated copy/allele of X-linked gene is needed to manifest the disease?

Answer 5

1 (one)

Question 6

Among female, who are affected by X-linked dominant disorder? heterozygous/homozygous?

Answer 6

both

Question 7

If father normal + mother heterozygote (affected), what are the chances among children?

(can use pen & paper)

Answer 7

Each daughter has 50% chance of being heterozygous (affected), 50% chance to be normal

Each son has 50% chance to be affected, 50% chance to be normal

Question 8

If father normal + mother homozygote affected, what are the chances among children?

(can use pen & paper)

Answer 8

All daughters will be heterozygote affected (Each has 100% chance)

All sons will be affected (Each has 100% chance)

Question 9

If father affected + mother homozygote affected. what are the chances among children?

(can use pen and paper)

Answer 9

All daughters will be homozygote affected (each has 100% chance)

All sons will be affected (each has 100% chance)

Question 10

If father affected + mother heterozygote (affected), what are the chances among children?

(can use pen and paper)

Answer 10

Each daughter has 50% chance to be heterozygote affected, and 50% chance to be homozygote affected

Each son has 50% chance to be affected and 50% chance to be normal

Question 11

If father affected + mother normal, what are the chances among children?

(can use pen and paper)

Answer 11

All daughters will be heterozygous affected (Each has 100% chance)

All sons will be normal

Question 12

If a female is affected (heterozygote) with X-linked dominant disorder, what is the family history?

Answer 12

If she is heterozygous, >>> her father is normal/affected, mother is normal/affected (heterozygote/homozygote)

Question 13

If a female is affected (homozygote) with X-linked dominant disorder, what is her family history?

Answer 13

only possible if mother is homozygote (affected) and father is affected

Question 14

If a male is affected, what can be predicted about his parents?

Answer 14

His mother is affected (homozygote/heterozygote)

[father cannot be predicted]

Question 15

Son gets his X-linked dominant disorder from whom?

Answer 15

Mother

Question 16

‘NO male to male transmission’ is applicable for which diseases?

Answer 16

X linked recessive disorder

X linked dominant disorder

Question 17

In the exam, if the question tells ‘one spouse is affected’, what is presumed about another spouse?

Answer 17

another spouse is normal

Question 18

In the exam, if the question tells ‘women is affected with X-linked dominant disorder’, what hetero/homozygote is she?

Answer 18

if not mentioned, think she is heterozygote.

homozygote will be mentioned

Question 19

If mother has an X-linked dominant disoder, what are the chances among children?

(can use pen and paper)

Answer 19

Each pregnancy (son or daughter) will have 50% chance to be affected

(presumed she is heterozygote & father is normal)

Question 20

Can a male be homozygote with X-linked disease?

Answer 20

NO

Male have only one X chromosome

Question 21

If father is affected, what are the chances among children?

(can use pen and paper)

Answer 21

NO son will be affected

All daughters will be affected (heterozygote)

(presumed mother is normal)

Question 22

What is the carrier profile in X-linked dominant disorder?

Answer 22

NO carrier.

One affected X-chorosome will make male/female affected.

Question 23

What is the variation of manifestation of X-linked dominant disorders in male and female?

Answer 23

Females are less severely affected

Males are frequently lethal

Question 24

Why females are less severely affected in X-linked dominant disorders?

Answer 24

Lyonisation (X-inactivation) in them

Question 25

Why are males frequently lethal in X-linked dominant disorders?

Answer 25

They have only one single X chromosome

(And they do NOT have lynisation)

Question 26

Alport syndrome: variation of features in male and female

Answer 26

Though X-linked dominat, it shows more severe expression in males

In males: At early life/boyhood >>> deafness + renal failure

In females: At early life >>> haematuria + clinically well; At later life: HTN (in 1/3rd), renal failure (up to 15%), deafness

Question 27

Fragile X syndrome: variation of features in male and female

Answer 27

Though X-linked dominat, it shows more severe expression in males (usually, but not always)

In males: significant learning disabilities

In females of full-mutation carriers: up to 50% have some learning ot behavioural problems (less severe than boys): usually, not always

Question 28

Incontinentia pigmenti (IP): variation of features in male and female

Answer 28

Males: emryonically lethal >> miscarriage

Females: In infancy > vesicular skin lesions, hypodonia (small teeth), alopecia, retinal & other abnormalities

Later > they have increased rate of miscarriages due to affected male conceptions

Question 29

Rett syndrome: variation of features in male and female

Answer 29

Males: Emryonically lethal >> so, miscarriage & males are rare + they are severely affected

Females: developmental regression, progressive microcephaly, stereotypical hand movements, irregular breathing patterns

Question 30

Rett syndrome: offsprings

Answer 30

Severe enough conditions that affected individuals do NOT reproduce

Such mutations generally arise anew in individuals

Question 31

Periventricular nodular heteroptia: variation of features in male and female

Answer 31

Males: Embryonically lethal >> miscarriage

Females: epilepsy + occasional learning disability

Question 32

Which X-linked dominant disorders are embryonically lethal in male?

Answer 32

Incontinentia pigmenti

Periventricular nodular heteroptia

Rett syndrome

Question 33

Name an X-linked dominant disorder with Skewed birth ratio

(excess of miscarriages due to affected male conception)

Answer 33

Incontinentia pigmenti

Question 34

Which X-linked dominant disorder is NOT embyonically lethal?

Answer 34

Vitamin D resistant Rickets

Males & Females get affected & pass the affected X chromosome to their children