DUCHENNE MUSCULAR DYSTROPHY

·         X-linked Recessive disorder (Therefore, seen only in males)

·         a.k.a. Pseudohypertrophic Muscular Dystrophy

·         Most common hereditary neuromuscular disease.

·         Characterized by PAINLESS degeneration and fibrosis of muscles (no muscle spasms/myalgia)

·         Genetics-

§  Locus- Xp21.2 (codes for dystrophin) [Dystrophin gene- one of the largest genes in the body]

§  Defects- Deletions (65%) >> Duplications (7%)

§  Dystrophin connects actin filaments to β-dystroglycan (a transmembrane protein in the sarcolemma), thus connecting actin to sarcolemma.

§  Dystrophin-glycoprotein complex confers stability to sarcolemma

§  Absence of dystrophin secondarily causes reduction in the number of dystrophin-associated sarcolemmal glycoproteins → increased susceptibility of sarcolemma to necrosis.

§  Carriers may show no or only mild weakness (only in some cases, may exhibit weakness due to lyonisation of the normal X-chromosome)

·         Clinical Manifestations-

§  Asymptomatic at birth (mild hypotonia may be seen)

§  Skeletal Muscle Abnormalities- (Progressive)

§  Poor head control in infancy- may be the first sign.

§  Early gross motor developmental milestones are usually achieved appropriately or may be delayed.

§  Deep tendon reflexes are usually present, but may disappear in later stages due to excessive weakness of the muscles.

§  Proximal weakness >> Distal weakness

§  Lower limb weakness >> Upper limb weakness

§  Hip Girdle weakness- appears by beginning of 2 yrs.

§  Lordotic posture and muscle wasting

§  Gower’s sign- start to appear by 3 yrs and fully manifest by 5-6 yrs.

§  Trendelenburg/Waddling gait

§  Pseudohypertrophy of muscles- Calf (typical), gluteal and shoulder

§  Contractures of iliotibial tract & Achilles tendon - associated with toe-walking and lordotic posture.

§  Confinement to wheelchair usually by 12 yrs (It accelerates development of painful scoliosis)

§  Respiratory muscle weakness + Chest deformity + Scoliosis – Impaired pulmonary function.

§  Pharyngeal muscle weakness- ↑ risk of aspiration.

§  Intellectual impairment

§  Cardiomyopathy - its severity doesn’t correspond to severity of musculoskeletal involvement

§  Death (by 18 yrs)- due to:-

§  Respiratory failure

§  Heart failure

§  Pneumonia

§  Aspiration

·         Lab features and Diagnosis

§  ↑↑ Serum CK (Creatinine Kinase) – 20-100 times normal

§  ↑ even at birth and pre-symptomatic patients.

§  ↑ in female carriers

§  Electromyography (EMG) – non-specific features of myopathy in absence of any nerve abnormalities

§  Echocardiography

§  Muscle Biopsy- diagnostic

§  Scattered degenerating & regenerating myofibrils.

§  Mononuclear cell infiltrate

§  Endomysial connective tissue proliferation

§  Dense fibers

§  Calcification within myofibrils

§  Western blot analysis for dystrophin protein

§  Immunohistochemical staining of muscle with dystrophin antibodies.

·         Treatment

§  No curative treatment

§  Glucocorticoids - ↓ rate of progression (long term adverse effects may outweigh the benefits)

§  Frequent monitoring of cardiac complications

§  Supportive treatment for:-

§  Cardiac decompensation

§  Respiratory infections

§  Physiotherapy (delays formation of contractures)

§  Calcium supplementation

§  Diet restrictions to prevent obesity but maintenance of adequate nutritional status.