X-linked Dominant Disorders Flashcards
What is the mnemonic for X-linked dominant disorders?
FAIR
What are the X-linked dominant disorders?
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
Which X-linked dominant disease is a complex X-linked?
Fragile X syndrome
What is the inheritence pattern Alport syndrome?
>80% is X-linked dominant
Few cases are ADAS (Autosomal Dominant Alport Syndrome)
How many mutated copy/allele of X-linked gene is needed to manifest the disease?
1 (one)
Among female, who are affected by X-linked dominant disorder? heterozygous/homozygous?
both
If father normal + mother heterozygote (affected), what are the chances among children?
(can use pen & paper)
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
If father normal + mother homozygote affected, what are the chances among children?
(can use pen & paper)
All daughters will be heterozygote affected (Each has 100% chance)
All sons will be affected (Each has 100% chance)
If father affected + mother homozygote affected. what are the chances among children?
(can use pen and paper)
All daughters will be homozygote affected (each has 100% chance)
All sons will be affected (each has 100% chance)
If father affected + mother heterozygote (affected), what are the chances among children?
(can use pen and paper)
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
If father affected + mother normal, what are the chances among children?
(can use pen and paper)
All daughters will be heterozygous affected (Each has 100% chance)
All sons will be normal
If a female is affected (heterozygote) with X-linked dominant disorder, what is the family history?
If she is heterozygous, >>> her father is normal/affected, mother is normal/affected (heterozygote/homozygote)
If a female is affected (homozygote) with X-linked dominant disorder, what is her family history?
only possible if mother is homozygote (affected) and father is affected
If a male is affected, what can be predicted about his parents?
His mother is affected (homozygote/heterozygote)
[father cannot be predicted]
Son gets his X-linked dominant disorder from whom?
Mother
‘NO male to male transmission’ is applicable for which diseases?
X linked recessive disorder
X linked dominant disorder
In the exam, if the question tells ‘one spouse is affected’, what is presumed about another spouse?
another spouse is normal
In the exam, if the question tells ‘women is affected with X-linked dominant disorder’, what hetero/homozygote is she?
if not mentioned, think she is heterozygote.
homozygote will be mentioned
If mother has an X-linked dominant disoder, what are the chances among children?
(can use pen and paper)
Each pregnancy (son or daughter) will have 50% chance to be affected
(presumed she is heterozygote & father is normal)
Can a male be homozygote with X-linked disease?
NO
Male have only one X chromosome
If father is affected, what are the chances among children?
(can use pen and paper)
NO son will be affected
All daughters will be affected (heterozygote)
(presumed mother is normal)
What is the carrier profile in X-linked dominant disorder?
NO carrier.
One affected X-chorosome will make male/female affected.
What is the variation of manifestation of X-linked dominant disorders in male and female?
Females are less severely affected
Males are frequently lethal
Why females are less severely affected in X-linked dominant disorders?
Lyonisation (X-inactivation) in them
Why are males frequently lethal in X-linked dominant disorders?
They have only one single X chromosome
(And they do NOT have lynisation)
Alport syndrome: variation of features in male and female
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
Fragile X syndrome: variation of features in male and female
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
Incontinentia pigmenti (IP): variation of features in male and female
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
Rett syndrome: variation of features in male and female
Males: Emryonically lethal >> so, miscarriage & males are rare + they are severely affected
Females: developmental regression, progressive microcephaly, stereotypical hand movements, irregular breathing patterns
Rett syndrome: offsprings
Severe enough conditions that affected individuals do NOT reproduce
Such mutations generally arise anew in individuals
Periventricular nodular heteroptia: variation of features in male and female
Males: Embryonically lethal >> miscarriage
Females: epilepsy + occasional learning disability
Which X-linked dominant disorders are embryonically lethal in male?
Incontinentia pigmenti
Periventricular nodular heteroptia
Rett syndrome
Name an X-linked dominant disorder with Skewed birth ratio
(excess of miscarriages due to affected male conception)
Incontinentia pigmenti
Which X-linked dominant disorder is NOT embyonically lethal?
Vitamin D resistant Rickets
Males & Females get affected & pass the affected X chromosome to their children
