Summary Duchenne Muscular Dystrophy presents in young males between the ages of 2 and 6 years with progressive muscle weakness. It is caused by an X-linked recessive mutation leading to the absence of dystrophin protein. Labs demonstrated markedly elevated CPK leves and diagnosis is made with DNA testing for dystrophin. Treatment involves a multidisciplinary approach to address cardiomyopathy, pulmonary dysfunction, scoliosis, and foot deformities. Epidemiology Most common hereditary neuromuscular disease first described by Guillaume-Benjamin-Amand Duchenne de Boulogne, a French neurologist who first described the condition in 1861 Prevalence 2-3/10,000 Demographics affects young males only age of symptom onset is between 2-6 years of age Etiology Pathophysiology dystrophin expressed in striated and cardiac muscle, brain, and retina large cytoskeletal protein login to view 1 more bullet dystrophin absence leads to loss of DGC leading to excessive membrane fragility and permeability dysregulation of calcium homeostasis oxidative damage poor muscle fiber regeneration repeated cycles of necrosis and regeneration login to view 1 more bullet progressive replacement of muscle tissue with fibrous and fatty tissue skeletal and cardiac muscle lose elasticity and strength Genetics X-linked recessive Xp21.2 dystrophin gene defect due to point deletion and nonsense mutation one third of cases result from spontaneous mutations carrier females typically unaffected, however 2.5-20% of female carriers may still show symptoms Lyon hypothesis login to view 1 more bullet Associated conditions orthopaedic manifestations calf pseudohypertrophy scoliosis equinovarus foot deformity joint contractures nonorthopaedic conditions cardiomyopathy static encephalopathy Physical Exam Symptoms early development typically normal within first few years delayed milestones slower growth velocity may present with mild hypotonia or poor head control progressive weakness affecting proximal muscles first (begins with gluteal muscle weakness) gait abnormalities begin around age 2 to 3 years delayed walking toe walking clumsy, waddling gait difficulty climbing stairs, hopping, or jumping decreased motor skills mild intellectual impairment pharyngeal weakness aspiration, nasal regurgitation of liquids, and nasal quality of voice less common presentations incontinence of urine and stool (late manifestation) malignant hyperthermia Physical exam calf pseudohypertrophy (infiltration of normal muscle with connective tissue) deep tendon reflexes present (unlike spinal muscular atrophy) contractures elbows, hips, knees, ankles lumbar lordosis compensates for gluteal weakness neurogenic scoliosis Gower's sign rises by walking hands up legs to compensate for gluteus maximus and quadriceps weakness Trendelenburg gait fractures frequent falls Evaluation Labs markedly elevated CPK levels (10-200x normal) CPK leaks across defective cell membrane login to view 1 more bullet elevated levels in 80% of asymptomatic carriers login to view 1 more bullet Muscle biopsy connective tissue infiltration and foci of necrosis muscle fiber necrosis with mononuclear cell infiltrate absent dystrophin with staining DNA testing shows absent or near-absent dystrophin protein typically <5% of normal quantity of dystrophin EMG myopathic decreased amplitude, short duration, polyphasic motor normal conduction velocities Imaging Radiographs usually to characterize fractures due to multiple falls nonspecific features translucent soft tissues (fatty muscle replacement) scoliosis hypoinflated lungs cardiomegaly MRI typical pattern of muscle involvement upper limb login to view 2 more bullets lower limb login to view 4 more bullets Echocardiogram dilated cardiomyopathy present in all patients by late teens/early 20s Differential Similarity and Distinguishing features of differential diagnosis Similar traits to Duchenne's Distinguishing traits from Duchenne's Becker's Calf pseudohypertrophy Markedly elevated CPK X-linked transmission Becker's has slower progression of weakness with diagnosis made later (~8 yrs) and longer life expectancy Prone to cardiomyopathy Dystrophin decreased instead of absent due to in-frame mutation Spinal muscular atrophy Proximal weakness Onset of weakness is earlier in childhood Absent deep tendon reflexes and fasciculations CPK levels are normal Pseudohypertrophy is absent Emery-Dreifuss dystrophy Similar clinical picture No calf pseudohypertrophy CPK levels near normal Elbow and ankle contractures develop early Limb girdle dystrophy Progressive motor weakness No calf pseudohypertrophy CPK levels are only mildly elevated Guillain-Barre syndrome Acute onset of weakness Absent deep tendon reflexes CPK levels are normal CSF fluid analysis is diagnostic Treatment Nonoperative corticosteroid therapy indications login to view 1 more bullet goals login to view 1 more bullet outcomes login to view 7 more bullets side effects login to view 9 more bullets medications login to view 10 more bullets oligonucleotide splicing modulators gene therapy agents login to view 2 more bullets mechanism login to view 4 more bullets indications login to view 2 more bullets advantages login to view 2 more bullets disadvantages login to view 6 more bullets ACE inhibitor, beta-blockers slow progression of cardiomyopathy and heart failure regular EKC/echocardiogram surveillance login to view 2 more bullets pulmonary care with nightly ventilation rehabilitation techniques login to view 4 more bullets nutrition risk of malnutrition, obesity, osteoporosis Operative soft tissue releases to prolong ambulation indications login to view 1 more bullet techniques login to view 4 more bullets postoperative care login to view 1 more bullet scoliosis surgery (see below) Scoliosis Introduction considered a neurogenic curve curve progresses rapidly from age 13 to 14 years begins with mild hyperlordosis progresses with general kyphosis and scoliosis with varying degrees of pelvic obliquity login to view 1 more bullet progresses 1° to 2° per month starting at age 8 to 10 years patients may become bedridden by age 16 cardiac and pulmonary function studies should be obtained pre-operatively as significant declines in function of both organ systems may make spinal fusion too high-risk treatment is complicated by restrictive pulmonary disease (significant decrease in forced vital capacity) Treatment nonoperative bracing is contraindicated login to view 1 more bullet maintain ambulation for as long as possible login to view 2 more bullets operative instrumented posterior spinal fusion is the mainstay of treatment for Duchenne-associated scoliosis indications login to view 19 more bullets preoperative considerations login to view 9 more bullets Techniques login to view 13 more bullets Equinovarus Foot Introduction common foot deformity seen with Duchenne muscular dystrophy Pathoanatomy muscle imbalance secondary to muscle replacement with fibrofatty tissue Diagnosis made upon clinical exam Treatment nonoperative stretching, physical therapy, and night time AFO use operative Tendinoachilles lengthening with posterior tibialis tendon transfer, toe flexor tenotomies Prognosis Historical prognosis Most unable to ambulate independently by age 10 Most wheelchair dependent by age 15 Most die from respiratory weakness or cardiomyopathy by age 20 5-, 10, and 15-year survival rates without steroid therapy 100%, 72.1%, 27.9% With >1 year of steroid treatment Delays loss of ambulation by 3-4 years Delays loss of hand to mouth function by 5 years Delays loss of distal hand function by 6-8 years 76% lower mortality rate 5-, 10, and 15-year survival rates with steroid therapy login to view 1 more bullet