Duchenne and Becker Muscular Dystrophies (Dystrophinopathies)

Duchenne Muscular Dystrophy (DMD) This form presents in early childhood with delayed attainment of independent ambulation, difficulty running or climbing stairs, frequent falls, Gowers’ sign (the patient performs a specific “climbing” maneuver to rise from the floor), and enlargement of the calves (pseudohypertrophy). Over the years, there is a progressive worsening of muscle strength, primarily localized to the proximal lower limbs; without treatment, loss of independent ambulation typically occurs between ages 9 and 13. Patients then develop progressive weakness in the upper limbs. In the second decade of life, the onset of cardiomyopathy and respiratory failure occurs, which affects life expectancy. In the final stages of the disease, patients may present with severe tetraplegia, involving distal muscles as well, and dysphagia. Variable cognitive involvement may also be observed.

Becker Muscular Dystrophy (BMD) BMD has a later onset, generally during adolescence or adulthood. Patients report cramps, myalgias, and progressive muscle weakness, which leads to the loss of independent ambulation in only a subset of patients. A variable proportion of subjects may exhibit cardiac involvement, which can sometimes be isolated and serve as the initial symptom. Respiratory impairment may also be present. Life expectancy is generally normal.

Carrier Status Female carriers are generally asymptomatic or may present with a slight elevation in CPK levels. In a small percentage of cases (2.5-10%), they may experience muscular symptoms (cramps, myalgias, weakness) or dilated cardiomyopathy (7-18% of cases).

The diagnosis of Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD) is based on several tests that allow for the confirmation of the disease and the differentiation between the two forms.

• Laboratory Tests: Significantly elevated creatine kinase (CK) levels (10-100 times higher than normal in DMD, variable in BMD).
• Instrumental Tests: Electromyography (myopathic pattern) and muscle MRI (fibro-fatty replacement) are useful for diagnostic purposes. Echocardiogram, Holter-ECG (cardiac monitoring), spirometry, and overnight pulse oximetry (respiratory function monitoring) are essential for follow-up. For female carriers, periodic cardiological screenings are recommended due to the risk of developing cardiomyopathy.
• Genetic Analysis: MLPA (Multiple Ligation-dependent Probe Amplification) testing to detect deletions or duplications in the DMD gene is positive in approximately 70% of DMD cases and 90% of BMD cases. In the remaining cases, direct sequencing of the DMD gene can identify point mutations. Carrier testing and prenatal diagnosis are possible if the familial mutation is known.
• Muscle Biopsy: Rarely necessary; it is primarily used for differential diagnosis when genetic testing is inconclusive.