Sex

• Duchenne and Becker muscular dystrophy almost exclusively affect males because of the X-linked inheritance pattern.
• Rarely, skewed random inactivation of healthy copies of the X chromosome leads to the Becker/Duchenne phenotype in females who carry the dystrophin mutation.
• Females with Turner syndrome (XO) or uniparental disomy or those who have translocations between the X and autosomal chromosomes may similarly manifest the Duchenne phenotype. Elevations of creatine phosphokinase (CPK) level are found in two thirds of female carriers, the vast majority of whom are clinically asymptomatic.

• Age

  • Duchenne muscular dystrophy clinically manifests in patients aged 3-7 years, with development of lordosis, a waddling gait, and the Gowers sign. Calf pseudohypertrophy follows 1-2 years later. Most patients are wheelchair bound by age 12 years.

  • History

    • Waddling gait, manifesting in children aged 2-6 years, is often the first symptom in patients with Duchenne muscular dystrophy and is secondary to hip girdle muscle weakness.
    • Sometimes a young boy may come to medical attention because of elevated liver function enzymes (AST, ALT), and in such cases serum creatine kinases CK and GGT levels should be checked prior to considering liver biopsies. Occasionally a young boy may be referred for speech delay or learning problems.
    • Most children with dystrophinopathy have IQs about one standard deviation lower than the general population, but certainly plenty of exceptions exist. The low intellectual skills, such as cognitive issues (learning differences, attention deficit hyperactivity disorder, obsessive-compulsive disorder, pervasive developmental disorder, mentalretardation), are seen in up to 30% of patients with dystrophinopathy. 
    • In some older boys , dilated cardiomyopathy findings may lead to diagnoses such as viral or idiopathic cardiomyopathy when in fact a dystrophin mutation may be the underlying reason.

    • Laboratory Studies

      Serum creatine phosphokinase (CPK)

      Imaging Studies

      • Scoliosis frequently ensues in patients with Duchenne muscular dystrophy, particularly after they are wheelchair dependent. Radiographs of the spine are important for screening and evaluating the degree of scoliotic deformity.
      • • Electromyography

          • Electromyography (EMG), even though not diagnostic, narrows the differential diagnosis by effectively excluding primarily neurogenic processes such as spinal muscular atrophy.
          • In general, the proximal muscles of the lower extremities may exhibit the more prominent EMG findings. A sufficient number of muscles need to be sampled to establish the presence of a diffuse process such as a dystrophy. The more revealing findings will be obtained in muscles of intermediate involvement with respect to weakness.
          • The motor unit action potentials (MUAPs) in patients with Duchenne or Becker muscular dystrophy are typically of short duration, particularly the simple (ie, nonpolyphasic) MUAPs. MUAP amplitudes are variable (normal to reduced) and they are typically polyphasic from the variability in muscle fiber diameters, resulting in longer MUAP durations. Early recruitment of MUAPs may be seen. If muscle fiber loss is severe, then what appears to be a loss of motor units may be seen with fast firing individual spikes. The latter are distinguished from neurogenic processes by their generally lower-than-normal amplitudes and reduced area of spikes.
          • Fibrillation potentials and positive sharp waves, which represent spontaneously depolarizing muscle fibers bereft of nervous innervation, are encountered in active disease as necrosis engulfs the motor endplate or separates the endplate from other portions of the muscle fiber. These may be difficult to see in some muscles, requiring higher-than-usual sensitivity settings on the amplifier.
        • Molecular diagnosis

          • Individuals with Duchenne or Becker muscular dystrophy can be reliably and accurately detected from peripheral blood samples in nearly all cases. If uninformative deletion/duplication genetic tests have resulted, direct sequencing of the dystrophin gene is a viable option. Other innovative methods have been devised for accurate noninvasive diagnosis.
            • Currently, most laboratories use multiplex PCR amplification to examine deletion "hotspots," which account for approximately 59% of all mutations. This method has a 98% detection rate for deletions.
            • Duplications, which account for 5% of mutations, can be detected by several different quantitative techniques, including Southern blot, quantitative PCR, multiplex amplifiable probe hybridization (MAPH), and multiplex ligation-dependent probe (MLPA). These techniques are also highly sensitive for detecting deletions.
            • The remaining one third of the mutations are composed of subexonic sequences, of which 34% are nonsense mutations, 33% are frameshifts, 29% are splice site mutations, and 4% are missense mutations. These mutations can be screened for by using techniques such as denaturing high-performance liquid chromatography (dHPLC); single- stranded conformational polymorphism analysis with single condition amplification internal primers (SCAIP) or detection of virtually all mutations (DOVAM), a robotically enhanced multiplexed method; or denaturing gradient gel electrophoresis.

            • Histologic Findings

              Few muscle biopsies are as instantly recognizable as those of patients with Duchenne muscular dystrophy. Features of Duchenne muscular dystrophy are reminiscent of a tissue battlefield after a major conflict, with necrotic muscle fibers littering the landscape. Widespread muscle necrosis leads to angulated fibers, central nuclei, and considerable fiber size variation, with regenerating cells in different stages of atrophy and regrowth.

              Medical Care and Treatment

              Supportive care

              Supportive care requires a coordinated and multidisciplinary team approach including primary care physician, neurologist, pulmonologist, cardiologist, endocrinologist, physical therapist, orthotist, mobility expert, nutritionist, orthopedic surgeon, social worker, genetic counselor, psychologist/psychiatrist, palliative care team, and school staff (including teacher, counselors, and nurses).

              • Plays a crucial role in maximizing functional status and tone, as well as in delaying wheelchair dependence.

                • Daily joint-stretching exercises prevent the debilitating onset of contractures.
                • Night splints can have a favorable influence.
                • Judicious use of tendon release surgeries may prolong ambulation by as long as 2 years.
                • Braces, such as ankle-foot orthoses and knee-ankle-foot orthoses, can be adjuncts in prolonging the period of mobility and delaying wheelchair dependency. Maintaining the ability to stand, even without mobility, delays the onset of many contractures and scoliosis. This may require elaborate bracing mechanisms and often is poorly tolerated and expensive. Because bracing delays but does not prevent the eventual outcome, this option is less frequently pursued now than in the past.