Diagnosis of dystrophinopathies: review for the clinician

The dystrophinopathies are muscle disorders due to an abnormality of an Xp21-linked gene which produces the dystrophin protein. The most common of these disorders are the Duchenne and Becker muscular dystrophies. Modern molecular genetic techniques enable reliable diagnosis and prognosis in many patients, but there are occasional pitfalls. Furthermore, the clinical spectrum of the dystrophinopathies are now such that the clinician needs to be aware of a broader range of clinical disorders that require analysis of the dystrophin gene and its product, not just those that mirror a classic Duchenne or Becker muscular dystrophy picture. This spectrum ranges from a severe form presenting at birth to asymptomatic elevation of CK. Females may be manifesting carriers or present as a severe phenotype when the abnormal gene is expressed as an X-autosome translocation or monosomy X. Laboratory diagnosis and prognosis can be made most accurately by using both DNA analysis at the dystrophin gene and immuno-analysis of muscle with antibodies directed against different regions of the protein product. This review describes some exemplary patients, suggests a clinical classification for dystrophinopathies, and outlines a diagnostic approach.