MELAS Inheritance from Father to Male Offspring
A male with MELAS syndrome cannot transmit the disease to his offspring, regardless of the child's sex, because mitochondrial DNA is exclusively inherited through the maternal line. 1
Mitochondrial Inheritance Pattern
MELAS follows strict maternal inheritance because:
- Mitochondrial DNA is transmitted exclusively from the mother to all her children through the cytoplasm of the egg cell 1
- Males with mitochondrial DNA mutations cannot pass these mutations to their offspring because sperm contribute only nuclear DNA to the fertilized egg, not mitochondrial DNA 1
- The A3243G mutation in mitochondrial DNA (the most common cause of MELAS, present in approximately 80% of patients) is maternally inherited 2, 3
Risk Assessment for Male Patients
For a male patient with MELAS syndrome:
- The risk of transmission to any offspring (male or female) is 0% 1
- His children will not inherit the mitochondrial mutation from him 1
- However, if his female partner carries a mitochondrial mutation, she could transmit it to their children 1
Important Clinical Caveat
While MELAS is typically caused by mitochondrial DNA mutations, rare cases may involve nuclear DNA mutations:
- If the patient's condition were caused by a nuclear DNA mutation (extremely rare), inheritance would follow autosomal dominant, autosomal recessive, or X-linked patterns 1
- For autosomal dominant nuclear mutations, there would be a 50% risk to offspring 1
- Genetic testing is essential to confirm the specific genetic basis and distinguish between mitochondrial versus nuclear DNA mutations 1
Genetic Counseling Recommendations
When counseling male MELAS patients:
- Emphasize the zero risk of transmission from father to children for mitochondrial DNA mutations 1
- Focus on the importance of maternal family history, as the mother's lineage determines risk 1
- Confirm the genetic basis through molecular testing to rule out rare nuclear DNA causes 1
- Assess the partner's family history for any mitochondrial disorders 1