Hemophilia & Genetic Inheritance
Hemophilia is an inherited genetic disorder caused by mutations or deletions in genes located on the X chromosome that encode for blood clotting factors (theF8gene for Factor VIII and theF9gene for Factor IX).
X-Linked Recessive Inheritance Pattern
Because the genes responsible for Hemophilia A and B reside on the X chromosome, the inheritance pattern differs fundamentally between biological males (XY) and females (XX):
Inheritance Rules:
- Males (XY): Possess only one X chromosome (inherited from their mother). If their single X chromosome bears the hemophilia mutation, they will manifest the bleeding disorder. Father-to-son transmission is genetically impossible.
- Females (XX): Possess two X chromosomes. A female who inherits one affected X chromosome is acarrier. Due to Lyonization (random X-inactivation), carriers usually have enough circulating factor (~30%–70%) to avoid major bleeds, though some experience mild bleeding tendencies.
Transmission Probabilities
Case 1: Carrier Mother and Unaffected Father
In each pregnancy:
- 50% chance that a male child will have hemophilia.
- 50% chance that a female child will be an asymptomatic or mild carrier.
Case 2: Father with Hemophilia and Unaffected Mother
In each pregnancy:
- 100% of daughters will inherit their father's affected X chromosome and become obligate carriers.
- 0% of sons are affected (sons receive the unaffected Y chromosome from the father).
Spontaneous / De Novo Mutations
In approximately 30% of all newly diagnosed hemophilia cases, there is no previous family history of bleeding disorders. These cases arise spontaneously due to a new (de novo) mutation during gametogenesis in the mother or child. Once established, the mutation is inherited by subsequent generations according to X-linked rules.
The Hemophilia Society Rajkot offers carrier screening assistance, pedigree mapping, and family genetic counseling to support affected families.