Symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers

Symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers (also known as manifesting carriers of DMD/BMD or symptomatic DMD/BMD carrier females) refers to a condition in which females who carry a heterozygous pathogenic variant in the DMD gene on the X chromosome develop clinical symptoms of muscular dystrophy. While Duchenne and Becker muscular dystrophies predominantly affect males, a subset of female carriers — estimated at 2.5% to 19% depending on the study and definition used — develop symptoms ranging from mild to severe. The condition primarily affects the skeletal muscular system and the heart. Clinical manifestations in symptomatic female carriers are highly variable. Skeletal muscle involvement can range from mild proximal muscle weakness, exercise intolerance, and muscle cramps to progressive limb-girdle weakness that may eventually require wheelchair use, though severe presentations resembling classic Duchenne muscular dystrophy are rare. Elevated serum creatine kinase (CK) levels are commonly observed. Cardiac involvement is a significant concern and may include dilated cardiomyopathy, left ventricular dysfunction, and arrhythmias, which can occur even in the absence of significant skeletal muscle symptoms. The mechanism underlying symptom manifestation in carriers is primarily attributed to skewed X-chromosome inactivation, where the X chromosome carrying the normal DMD allele is preferentially inactivated, leading to reduced or absent dystrophin expression in a proportion of muscle fibers. Other mechanisms such as X-autosome translocations or Turner syndrome (45,X) with a DMD mutation on the remaining X chromosome can also cause manifestation. There is no cure for this condition. Management is supportive and multidisciplinary, focusing on monitoring and treating cardiac complications with ACE inhibitors, beta-blockers, or other cardiac medications as needed. Physical therapy and rehabilitation help maintain mobility and muscle function. Regular cardiac surveillance with echocardiography and electrocardiography is strongly recommended for all female DMD carriers, regardless of skeletal muscle symptoms. Corticosteroids may be considered in cases with significant progressive weakness, though evidence in female carriers specifically is limited. Genetic counseling is essential for reproductive planning and family screening.

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