X-linked Recessive Disorders

Question 1

What is the mnemonic for X-linked recessive disorders?

Answer 1

An Oblivious Female Will Give Her Cool Boy Kids Her x-Linked Recessive Disorder

Question 2

What are the X-linked recessive disorders?

Answer 2

An = Androgren insensitivity syndrome (AIS)

Oblivious = Ocular albinism, Ornithine transcarbamoylase deficiency

Female = Fabry’s disease

Will = Wiscott Aldrich syndrome

Give = G6PD deficiency (favism)

Her = Hunter’s disease (Mucopolysaccaridosis type 2: MPS type 2)

Cool = Color blindness (Red-green)

Combined immunodeficiency (severe, SCID)

Chronic granulomatous disease

Boy = Becker muscular dystrophy (BMD)

Bruton’s agammaglobinemia

Kids = Kallman syndrome

Her = Haemophilia A, B

x-Linked = Lesch-Nyhan syndrome

Recessive = Retinitis pigmentosa

Disorders = Duchene muscular dystrophy

Question 3

What is the sex/gender status in X-linked recessive disorders?

Answer 3

Males are affected

Females are carrier (rarely affected)

Question 4

Is it possible for a male to be carrier?

Answer 4

NO

one affected ‘X’ makes them affected

Question 5

Is the possible for a female to be affected?

Answer 5

Yes

In 2 cases:

​1. Her father and mother both had the affected X OR

2. Turner’s syndrome (45, XO)

Question 6

If a boy is affected with X-linked recessive, what is his family history?

Answer 6

His mother was a carrier/affected

Question 7

Can a boy get his X-linked recessive/dominant disorder from his father?

Answer 7

NO

A boy gain only Y chromosome from father

Question 8

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

Answer 8

X-linked Recessive disorder

X-linked Dominant disorder

Mitochondrial disorder

Question 9

Will an affected male transmit the X-linked recessive disorder to his daughters?

Answer 9

Yes. Always to all his daughters.

Male gives his one X chromosome to daughter.

Question 10

If a female is carrier of an X-linked recessive disorder, what is her family history?

Answer 10

2 possibilities:

1. mother was affected/carrier

2. Father was affected

Question 11

If a female is affected (rare case), what are the possibilities?

Answer 11

3 possibilites:

1. She has Turner’s syndrome OR

2. Father is affected + mother is carrier OR

3. Father is affected + mother is affected (rarest)

Question 12

Homozygote (affected) females with X-linked recessive disorder are extremely rare, but in which race & disease it is bit commoner?

Answer 12

Afro-Caribbean community

G6PD deficiency

Question 13

Can both male/female be heterozygote & homozygote with X-linked recessive disorders?

Answer 13

NO.

Male can not be homozygote

Female can be both heterozygote and homozygote

Question 14

If father normal + mother carrier, what are the chances among children to inherit the disease?

(can use pen & paper)

Answer 14

Each daughter has 50% chance of being carrier

Each son has 50% chance of being affected

Question 15

If father normal + mother affected (homozygote), what are the chances among children to inherit the disease?

(can use pen and paper)

Answer 15

All daughters will be carrier (Each has 100% chance): none affected

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

Question 16

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

(can use pen & paper)

Answer 16

All daughters will be carrier (Each has 100% chance)

All sons will be normal

Question 17

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

(can use pen and paper)

Answer 17

Each daughter has 50% to be affected & 50% chance to be carrier

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

Question 18

If father affected + mother affected (homozygote), what are the chances among children to inherit the disease?

(can use pen and paper)

Answer 18

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

Question 19

Lesch-Nyhan syndrome is a cause of which rheumatological disease?

Answer 19

Gout

High uric acid production

Question 20

Which category of immunodeficiency is Wiskott-Aldrich syndrome?

Answer 20

Primary combined B and T cell deficiency

Question 21

Which gene is mutated in Wiskott-aldrich syndrome?

Answer 21

WASP gene

Question 22

Are all chronic granulomatous disease X-linked recessive?

Answer 22

>70% is X-linked recessive (Not all)

Varying pattern of inheritence

Question 23

Which diseases have varying pattern of inheritence (but majority being inherited has X-linked recessive)?

Answer 23

Chronic granulomatous disease

Primary immunodeficiency

Neutrophil disorders

Question 24

Ornithine transcarbamoylase deficiency: pathology, features

Answer 24

A urea cycle disorder

Affected males: neonatal onset

Carrier females: well in later life

Question 25

What does happen if a person with ornithine transcarbamoylase deficiency goes under stress or starvation?

Answer 25

Dangerous hyperammoniaemia

(Dangerously high ammonia in blood)

Question 26

‘In X-linked conditions, if one X is inactivated >> mild manifestation/phenotype’

- this phenomenon is called

Answer 26

Lyonisation

Question 27

‘Many X-linked conditions do NOT fit purely into recessive or dominant pattern + but have some more severe expression in males than females’

- example of them?

Answer 27

Alport syndrome

Fragile X syndrome

Fabry’s disease

Question 28

Fabry’s disease: variation of features in male and female

Answer 28

cardiovascular and renal defects + reduced life expectancy

(Female carriers have milder of it than male affected)

Question 29

What are the risks of female carriers of Duchene muscular dystrophy and Fabry’s disease?

Answer 29

Increased risk of cardiac complications

(In case of Duchene, they have 10% lifetime risk of overt cardiac failure)

Question 30

What are the recommendations for female carriers of Duchene muscular dystrophy and Fabry’s disease?

Answer 30

If non-symptomatic >>> 5-yearly screening by echocardiography

If symptomatic >>> more frequent screening