Makindo Medical Notes

Related Subjects: |Autosomal Recessive |X Linked Recessive |Autosomal Dominant |Li Fraumeni syndrome |Genetic Linkage |Cell Cycle |DNA replication

Overview of X-Linked Recessive Inheritance

X-linked recessive inheritance is a pattern of inheritance where a mutation in a gene on the X chromosome causes a trait or disorder to be expressed in males and typically carried by females. Males are more frequently affected because they have only one X chromosome, while females have two and can compensate with the normal allele on the other X chromosome.

Key Characteristics

• Affected Males:
  • Males with the mutated gene on their single X chromosome will express the disorder.
  • Affected males do not pass the disorder to their sons, as they pass their Y chromosome to male offspring.
• Carrier Females:
  • Females with one mutated gene are typically carriers and usually do not show symptoms due to the presence of a second, normal X chromosome.
  • Carrier females have a 50% chance of passing the mutated gene to their children.
  • Each son of a carrier mother has a 50% chance of being affected.
  • Each daughter of a carrier mother has a 50% chance of being a carrier.
• Skewed X-Inactivation:
  • In rare cases, carrier females can exhibit symptoms if the normal X chromosome is inactivated in a majority of cells.

Examples of X-Linked Recessive Disorders

• Haemophilia A and B:
  • Caused by mutations in the F8 and F9 genes, respectively.
  • Leads to deficient blood clotting and prolonged bleeding.
• Duchenne Muscular Dystrophy (DMD):
  • Caused by mutations in the DMD gene.
  • Results in progressive muscle weakness and degeneration.
• Color Blindness:
  • Commonly caused by mutations in the OPN1LW or OPN1MW genes.
  • Leads to difficulty distinguishing between certain colours, usually red and green.
• G6PD Deficiency:
  • Caused by mutations in the G6PD gene.
  • Results in haemolytic anaemia triggered by certain foods, infections, or medications.

Genetic Counseling and Testing

• Carrier Testing:
  • Genetic testing can identify carrier females who have a family history of X-linked recessive disorders.
• Prenatal Testing:
  • Can diagnose certain X-linked recessive disorders before birth through techniques like amniocentesis or chorionic villus sampling (CVS).
• Newborn Screening:
  • Some X-linked recessive disorders can be detected early through newborn screening programs, allowing for timely intervention and treatment.
• Genetic Counseling:
  • Provides information and support to individuals and families affected by or at risk of genetic disorders.
  • Helps in understanding the risks, implications, and options available.

Management and Treatment

• Symptomatic Treatment:
  • Focuses on managing symptoms and improving quality of life.
  • Examples include clotting factor replacement for haemophilia and physical therapy for Duchenne muscular dystrophy.
• Avoidance of Triggers:
  • For disorders like G6PD deficiency, avoiding known triggers (e.g., certain foods, medications) is crucial.
• Gene Therapy:
  • Emerging treatments aim to correct the underlying genetic defect.
• Supportive Care:
  • Includes nutritional support, mobility aids, and respiratory assistance for progressive conditions like Duchenne muscular dystrophy.

Summary

X-linked recessive inheritance involves mutations on the X chromosome that primarily affect males, while females are typically carriers. Understanding the key characteristics, examples of disorders, genetic counseling, and treatment options is crucial for managing and supporting individuals and families affected by these genetic conditions.