Duchenne Muscular Dystrophy Inheritance Pattern
Duchenne muscular dystrophy follows an X-linked recessive inheritance pattern, meaning males are predominantly affected because they possess only one X chromosome, while females are typically asymptomatic carriers. 1
Primary Inheritance Mechanism
Males manifest the disease because a single mutated dystrophin gene on their sole X chromosome results in complete disease expression, with an incidence of approximately 1 in 3,000 to 1 in 5,000 live male births. 1, 2
Females typically do not manifest DMD because they possess a second, normal X chromosome that compensates for the mutated gene through random X-inactivation. 1
Approximately two-thirds of DMD cases are maternally inherited, while the remaining one-third result from de novo mutations. 3
Rare Female Manifestation
While females are usually asymptomatic carriers, they can rarely manifest DMD through specific mechanisms:
When female carriers do develop symptoms, they typically present with mild to moderate dilated cardiomyopathy in the fifth decade of life with slowly progressive disease. 1, 2
Ultra-rare cases of symptomatic females occur through X-autosome translocations that disrupt the DMD gene combined with skewed X-inactivation (such as 99:1 ratios), leading to preferential inactivation of the normal X chromosome. 4
Hemizygosity for the mutated allele can be detected in symptomatic females using polymorphic dinucleotide (CA)n repeat markers within the dystrophin gene. 5
Critical Clinical Implications
Family screening is essential as approximately 30-50% of dilated cardiomyopathy cases in DMD families show inherited patterns. 1
Female carriers require lifelong cardiac surveillance given their significant risk of late-onset cardiomyopathy, even in the absence of skeletal muscle symptoms. 1, 2
Establishing carrier status in female relatives is crucial to restore reproductive confidence for non-carriers and facilitate reproductive options for confirmed carriers. 3
The X-linked recessive pattern means affected males cannot transmit the disease to their sons (who receive the Y chromosome), but all daughters of affected males will be obligate carriers. 1