Understanding the disorder and its importance
Neuromuscular disorders are a diverse group of conditions that affect the functioning of muscles due to problems with the nerves that control them or with the muscles themselves. Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) are two significant examples of these disorders. DMD is a genetic disorder characterised by progressive muscle degeneration and weakness due to the absence of dystrophin, a protein that helps keep muscle cells intact. SMA is a genetic disorder affecting the motor neurons in the spinal cord, leading to muscle weakness and atrophy. Understanding these disorders is crucial because they can have profound impacts on a child’s development, mobility and life expectancy. Early diagnosis and intervention can significantly improve outcomes, quality of life and in some cases, alter the natural course of the disease.
Signs and symptoms
The signs and symptoms of neuromuscular disorders can vary but often include muscle weakness and altered muscle tone. In DMD, early signs typically appear between ages two and five, including difficulty running, jumping or climbing stairs. The characteristic Gowers’ sign (using hands to ‘climb’ up one’s own body to stand up from a sitting position) may be present. Calf muscles often appear enlarged (pseudohypertrophy). As the disease progresses, weakness extends to the arms, neck and other areas. In SMA, symptoms can vary widely depending on the type, but generally include muscle weakness and atrophy, often more severe in the legs than arms. In severe infantile-onset SMA (Type 1), babies may have difficulty holding their head up, feeding or breathing. In less severe forms, children may have delayed motor milestones or difficulty with activities requiring strength. Both conditions can lead to complications such as scoliosis, contractures and respiratory issues.
When to seek neurological assessment
Neurological assessment should be sought if there are signs of delayed motor development, regression of motor skills, or persistent muscle weakness. For DMD, frequent falls, difficulty running or climbing stairs or the appearance of enlarged calf muscles should prompt evaluation. In SMA, failure to meet motor milestones (like sitting unsupported or walking) or loss of previously acquired motor skills are key indicators. Any unexplained muscle weakness, especially if progressive, warrants neurological assessment. For infants, poor muscle tone (hypotonia) or difficulty feeding should also lead to evaluation. Early assessment is crucial as some treatments, especially for SMA, are most effective when started early.
Investigation and treatment strategies
Investigation of suspected neuromuscular disorders typically begins with a detailed clinical history and physical examination. For DMD, initial screening often involves a blood test for creatine kinase (CK) levels, which are typically highly elevated. Genetic testing for mutations in the dystrophin gene confirms the diagnosis. For SMA, genetic testing for mutations or deletions in the SMN1 gene is the primary diagnostic tool. In some cases, electromyography (EMG) and nerve conduction studies may be performed. Muscle biopsy, once common, is now less frequently used due to advances in genetic testing.
Treatment strategies for DMD and SMA have evolved significantly in recent years. For DMD, corticosteroids remain a mainstay of treatment, helping to preserve muscle strength and function. Newer therapies include exon-skipping drugs and gene therapies, which aim to produce functional dystrophin. For SMA, revolutionary treatments have emerged, including nusinersen (a splice-modifying antisense oligonucleotide), onasemnogene abeparvovec (gene replacement therapy), and risdiplam (a small molecule that modifies SMN2 splicing). These treatments can significantly alter the course of the disease, especially when started early.
Supportive care is crucial for both conditions. This includes:
- Physical therapy to maintain muscle strength and flexibility, prevent contractures and optimise function.
- Occupational therapy to assist with activities of daily living and recommend adaptive equipment.
- Respiratory support, including assisted ventilation as needed.
- Cardiac monitoring and management, particularly in DMD.
- Nutritional support to maintain optimal weight and prevent complications.
- Orthopaedic interventions for scoliosis or contractures.
Regular multidisciplinary follow-up is essential to monitor disease progression and adjust management strategies. This typically involves neurologists, pulmonologists, cardiologists, orthopaedists, physical and occupational therapists and other specialists as needed.
Genetic counselling is an important aspect of care, providing information about inheritance patterns and options for future pregnancies. Psychological support for patients and families is also crucial, given the progressive nature of these conditions.
Research into new treatments for neuromuscular disorders is ongoing, with promising approaches in gene therapy, exon skipping and other novel therapeutics. Staying informed about clinical trials and research developments can be important for families affected by these conditions.
With advances in care and new therapeutic options, the outlook for many neuromuscular disorders has improved significantly. However, management remains complex and requires a comprehensive, multidisciplinary approach tailored to individual needs and disease course.