Neurology · Year 3 · from Neurology

Case 2: Duchenne Muscular Dystrophy

Patient Demographics

• Age: 4 years old
• Sex: Male

Chief Complaint

Mother: "He's having trouble keeping up with other kids. He can't run well and falls a lot."

History of Present Illness

Michael is a 4-year-old boy brought by his mother for evaluation of motor difficulties. She first noticed concerns around age 2.5-3 years when he seemed slower than peers to climb stairs and had difficulty getting up from the floor. He has always had large calf muscles, which she initially thought meant he was strong. Over the past year, his teachers have reported he can't keep up during physical activities and falls frequently. He has difficulty climbing playground equipment. His mother has noticed he uses a characteristic maneuver to stand from the floor - he puts his hands on his thighs and "walks" his hands up his legs. He cannot jump. He is not declining in any other developmental areas - his speech and cognition are normal.

Developmental History

• Language: Normal - speaks in full sentences
• Cognitive: Normal - learning colors, shapes, letters
• Fine Motor: Normal - draws, uses utensils
• Gross Motor: Delayed - walked at 18 months (late end of normal), always clumsy

Family History

• Mother: Healthy
• Father: Healthy
• Maternal uncle: "Had muscle problems, was in a wheelchair, died young" - mother doesn't know diagnosis

Physical Examination

• General: Alert, pleasant boy
• Vital Signs: Normal
• HEENT: Normal
• Cardiovascular: Regular rhythm, no murmur
• Respiratory: Clear
• Musculoskeletal:
• Calf pseudohypertrophy - firm, enlarged calves bilaterally
• Mild lumbar lordosis
• No contractures yet
• Neurological:
• Proximal weakness: Hip flexors 3+/5, hip extensors 3/5, knee extensors 4/5
• Distal strength preserved: 5/5 in feet
• Gower's sign POSITIVE - uses hands to climb up legs when rising from floor
• Waddling gait
• Cannot run
• Cannot hop on one foot
• Deep tendon reflexes: Reduced at knees, present at ankles
• No fasciculations
• Sensory: Normal

Clinical Image

Image: Sequential illustration of Gower's sign - the characteristic maneuver used by children with proximal muscle weakness (especially Duchenne muscular dystrophy) to rise from the floor by "walking" their hands up their thighs.

Image Source: Wikimedia Commons Attribution: Medical illustration, Public Domain URL: https://commons.wikimedia.org/wiki/File:Gowers_sign.png

Diagnostic Studies

Serum Creatine Kinase (CK):

• Result: 18,500 U/L (normal: <200 U/L)
• Massively elevated - consistent with muscular dystrophy

Genetic Testing:

• DMD gene analysis: Large deletion of exons 45-50 detected
• Confirms diagnosis of Duchenne muscular dystrophy (out-of-frame deletion)

Additional Studies:

• Echocardiogram: Normal LV function (baseline)
• Pulmonary function tests: Deferred (too young for reliable spirometry)
• ECG: Normal

Assessment and Diagnosis

Duchenne Muscular Dystrophy (DMD)

• X-linked recessive disorder
• Caused by mutations in dystrophin gene leading to absent dystrophin protein
• Progressive muscle weakness and degeneration
• Most common fatal genetic disorder of childhood

Natural History of DMD

Management Plan

Corticosteroid Therapy:

• Deflazacort 0.9 mg/kg/day (or prednisone 0.75 mg/kg/day)
• Prolongs ambulation by 2-3 years
• Preserves pulmonary and cardiac function
• Monitor for side effects: weight gain, behavior changes, growth suppression, osteoporosis, cataracts
• Start now while still ambulatory

Physical Therapy:

• Stretching program to prevent contractures (especially Achilles)
• Strengthening within limits (avoid eccentric exercise)
• Aquatic therapy
• Maintain mobility as long as possible

Cardiac Management:

• Baseline echocardiogram (completed - normal)
• Annual echocardiogram
• Start ACE inhibitor when LV dysfunction develops (or prophylactically by age 10)
• Annual ECG

Pulmonary Management:

• Baseline pulmonary function when able (typically age 5-6)
• Pulmonary function testing every 6-12 months
• Pneumococcal and influenza vaccinations
• Sleep study if symptoms of nocturnal hypoventilation
• Non-invasive ventilation (BiPAP) when indicated

Bone Health:

• Vitamin D and calcium supplementation
• DXA scan (baseline and periodic)
• Bisphosphonates if significant osteoporosis

Emerging Therapies:

• Exon skipping therapy - Eteplirsen (for exon 51 skipping) - not applicable to this patient's mutation
• Gene therapy trials ongoing
• Discussed with family - referred to neuromuscular center for clinical trial eligibility

Genetic Counseling:

• Mother is obligate carrier
• Risk to future male children: 50%
• Sisters should be tested (carrier status)
• Female carriers: screen for cardiomyopathy

Psychosocial Support:

• Parent support groups
• School accommodations (504 plan or IEP)
• Emotional support for patient and family
• Connected to MDA (Muscular Dystrophy Association)

Follow-Up

6-month visit:

• Stable on deflazacort
• Mild weight gain (2 kg above expected)
• Walking independently
• No contractures
• Started physical therapy program

Family counseling completed:

• Mother tested: DMD carrier confirmed
• Mother's echocardiogram: Normal
• Parents decided against further biological children; considering adoption

Teaching Points

1. Gower's sign indicates proximal muscle weakness - classic for DMD but not pathognomonic

1. Calf pseudohypertrophy - enlarged calves due to fatty/fibrous replacement of muscle

1. CK is markedly elevated (10,000-50,000+ U/L) in DMD - screen with CK if suspicion

1. DMD is X-linked recessive - affects boys; mothers are carriers

1. Corticosteroids (deflazacort or prednisone) are the mainstay of treatment - prolong ambulation and preserve cardiac/pulmonary function

1. Cardiac and pulmonary monitoring is essential - cardiomyopathy and respiratory failure are major causes of death

1. Genetic counseling is critical for family planning and identification of at-risk female carriers

1. New therapies emerging - exon skipping, gene therapy offer hope for some patients

All cases for this lecture as Markdown