X-linked Recessive Disorders Flashcards
What is the mnemonic for X-linked recessive disorders?
An Oblivious Female Will Give Her Cool Boy Kids Her x-Linked Recessive Disorder
What are the X-linked recessive disorders?
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
What is the sex/gender status in X-linked recessive disorders?
Males are affected
Females are carrier (rarely affected)
Is it possible for a male to be carrier?
NO
one affected ‘X’ makes them affected
Is the possible for a female to be affected?
Yes
In 2 cases:
1. Her father and mother both had the affected X OR
2. Turner’s syndrome (45, XO)
If a boy is affected with X-linked recessive, what is his family history?
His mother was a carrier/affected
Can a boy get his X-linked recessive/dominant disorder from his father?
NO
A boy gain only Y chromosome from father
‘NO male to male transmission’ is applicable for which diseases?
X-linked Recessive disorder
X-linked Dominant disorder
Mitochondrial disorder
Will an affected male transmit the X-linked recessive disorder to his daughters?
Yes. Always to all his daughters.
Male gives his one X chromosome to daughter.
If a female is carrier of an X-linked recessive disorder, what is her family history?
2 possibilities:
1. mother was affected/carrier
2. Father was affected
If a female is affected (rare case), what are the possibilities?
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)
Homozygote (affected) females with X-linked recessive disorder are extremely rare, but in which race & disease it is bit commoner?
Afro-Caribbean community
G6PD deficiency
Can both male/female be heterozygote & homozygote with X-linked recessive disorders?
NO.
Male can not be homozygote
Female can be both heterozygote and homozygote
If father normal + mother carrier, what are the chances among children to inherit the disease?
(can use pen & paper)
Each daughter has 50% chance of being carrier
Each son has 50% chance of being affected
If father normal + mother affected (homozygote), what are the chances among children to inherit the disease?
(can use pen and paper)
All daughters will be carrier (Each has 100% chance): none affected
All sons will be affected (Each has 100% chance)
If father affected + mother normal, what are the chances among children to inherit the disease?
(can use pen & paper)
All daughters will be carrier (Each has 100% chance)
All sons will be normal
If father affected + mother carrier (heterozygote), what are the chances among children to inherit the disease?
(can use pen and paper)
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
If father affected + mother affected (homozygote), what are the chances among children to inherit the disease?
(can use pen and paper)
All children (sons & daughters) will be affected (Each has 100% chance)
Lesch-Nyhan syndrome is a cause of which rheumatological disease?
Gout
High uric acid production
Which category of immunodeficiency is Wiskott-Aldrich syndrome?
Primary combined B and T cell deficiency
Which gene is mutated in Wiskott-aldrich syndrome?
WASP gene
Are all chronic granulomatous disease X-linked recessive?
>70% is X-linked recessive (Not all)
Varying pattern of inheritence
Which diseases have varying pattern of inheritence (but majority being inherited has X-linked recessive)?
Chronic granulomatous disease
Primary immunodeficiency
Neutrophil disorders
Ornithine transcarbamoylase deficiency: pathology, features
A urea cycle disorder
Affected males: neonatal onset
Carrier females: well in later life
What does happen if a person with ornithine transcarbamoylase deficiency goes under stress or starvation?
Dangerous hyperammoniaemia
(Dangerously high ammonia in blood)
‘In X-linked conditions, if one X is inactivated >> mild manifestation/phenotype’
- this phenomenon is called
Lyonisation
‘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?
Alport syndrome
Fragile X syndrome
Fabry’s disease
Fabry’s disease: variation of features in male and female
cardiovascular and renal defects + reduced life expectancy
(Female carriers have milder of it than male affected)
What are the risks of female carriers of Duchene muscular dystrophy and Fabry’s disease?
Increased risk of cardiac complications
(In case of Duchene, they have 10% lifetime risk of overt cardiac failure)
What are the recommendations for female carriers of Duchene muscular dystrophy and Fabry’s disease?
If non-symptomatic >>> 5-yearly screening by echocardiography
If symptomatic >>> more frequent screening
