Autosomal Dominant Disorders

Question 1

What is the mnemonic for common AD disorders?

Answer 1

DOMINANT POWERFUL VC 7H

Question 2

What are the Autosomal dominant disorders?

Answer 2

D = Dystrophia myotonica

O = Osteogenesis imperfecta (except type-2),

Ocular myopathy

M = Marfan’s syndrome

MODY (maturity onset Diabetes mellitus)

MEN (Multiple endocrine neoplasia)

I = Intermittent porphyria (Acute, AIP, also PCT & variegate porphyria)

N = Neurofibromatosis

A = ADPKD

Achondroplasia

Anti-thrombin III deficiency

Activated protein C resistance (Factor V leiden disease)

Alzheimer’s disease (the 5% inherited cases)

Arrythmogenic right ventricular cardiomyopathy (ARVC)

N = Noonan’s syndrome

T = Tuberous sclerosis

P = Peutz-Jegher’s syndrome

Protein C deficiency

O = Osler Weber Rendu Syndrome (HHT)

W = Wolf-Parkinson-White (WPW) syndrome

E = Ehlers-Danlos syndrome

R = Retinoblastoma

Romano-Ward syndrome(RWS)

F = Familial adenomatous polyposis (FAP) (inc. Gardner syndrome)

Familial hypercholesterolemia (type IIA, IIB, III, IV hyperlipidaemia)

Familial glucocorticoid remediable aldosteronism (Familial GRA)

U = Upington disease

L = Liddle’s syndrome

Li-Fraumeni syndrome

V = Von Hippel Lindau syndrome, Von-Willebrand’s disease (except typ-3)

C = Charcot Marie Tooth disease (including other HMSN)

Cowden’s syndrome

Catecholaminergic polymorphic ventricular tachycardia (CPVT)

H = Huntington’s disease

H = HOCM (Hypertrophic obstructive cardiomyopathy), Brugada syndrome

H = HNPCC (hereditary non-polyposis colorectal ca)

H = Hereditary spherocytosis

H = Hyperlipidemia type II

H = Hypokalaemic periodic paralysis

H = Hyperthermia (malignant)

Question 3

Who are the carrier and who are the affected?

Answer 3

NO Carrier state for autosomal dominant disorders

Both homozygous and heterozygous manifest disease

Question 4

What is the inheritence pattern among the offspring?

Answer 4

All offsprings has 50% chance of getting affected

Question 5

How many copy/allele of autosomal gene is needed to manifest the disease?

Answer 5

One (1)

Question 6

Who is affected? male or female?

Answer 6

Both

Question 7

Can anyone unaffected pass the disease?

Answer 7

No.

Only the affected (heterozygous/homozygous) can pass the disease

Question 8

What is the risk in first or subsequent pregnacies?

Answer 8

Same for all pregnancies.

In each pregnancy, child has 50% chance to be affected

Question 9

Do they skip generation or appear in every generation?

Answer 9

Normally, they appear in every generation

Question 10

What are the complicating factors?

Answer 10

• ​Non-penetrance
• Spontaneous mutaion

Question 11

What in non-penetrance?

Answer 11

Abnormal genotype, but

Normal phenotype = (lack of clinical signs & symptoms)

Question 12

What is spontaneous mutation?

Answer 12

New mutation in one of gamtes

Question 13

Give an example of non-penetrance?

Answer 13

40% of otosclerosis has non-penetrance

Question 14

Give example of spontaneous/new mutation

Answer 14

80% of Achondroplasia

Neurofibromatosis type 1

Question 15

Source of new mutation

Answer 15

Egg & Sperm

Egg is more common

Question 16

What are variable expression and reduced penetrance?

Answer 16

Variable expression = Within a family the severity may vary

Reduced penetrance = known mutation carrier + but clinically appears normal

Question 17

What is the type of maximum Autosomal dominant disorders?

Structural/Metabolic?

Answer 17

Structural

(has few exceptions)

Question 18

Almost all autosomal dominant disroders are structural.

But, as an exception, which are metabolic?

Answer 18

Hyperlipidaemia type 2

Hypokalaemic periodic paralysis

Malignant hyperthermia

AIP (Acute intermittent porphyria)

Familial hypercholesterolemia

Question 19

Which autosomal dominant condition has ‘short 4th and 5th metacarpals’?

Answer 19

Pseudohypoparathyroidism

Question 20

Which autosomal dominat condition is called ‘male Turner’s?

Answer 20

Noonan’s syndrome

Question 21

Which autosomal dominant condition has ‘blue sclera’?

Answer 21

Osteogenesis imperfecta

Question 22

Which type of osteogenesis imperfecta is NOT autosomal dominant?

Answer 22

Type 2

they are new mutation with no family history

Question 23

What is the inheritence of type 1 & 2 von-willebrand’s disease?

Answer 23

Autosomal dominant

Most common form is type 1 (80% of VWD)

Question 24

What is the inheritence of type 3 von-willebrand’s disease?

Answer 24

Autosomal Recessive

The most severe form of VWD

Question 25

What is the inheritence of all hepatic porphyria & which is the exceptional?

Answer 25

Autosomal dominant

(Except. Congenital erythropoietic porphyria)

Question 26

What is the inheritance pattern of CEP (Congenital erythropoietic purpura)?

Answer 26

Autosomal recessive

Question 27

Conditions prefixed as ‘hereditary’ or ‘familial’ is usually-?

Answer 27

Autosomal dominant

Exception: Hereditary haemochromatosis (AR)