Approach to Taking a History in Suspected Congenital Myasthenic Syndrome (CMS)
A thorough three-generation family history and detailed neuromuscular symptom assessment are essential first steps in evaluating patients with suspected Congenital Myasthenic Syndrome. The diagnostic approach should focus on identifying characteristic patterns of weakness, age of onset, and progression that distinguish CMS from acquired myasthenic disorders.
Key Components of History Taking
Age of Onset and Initial Presentation
- Document precise age of symptom onset (59% manifest in neonatal period, 35% in infancy) 1
- Identify initial presenting symptoms:
Pattern of Weakness and Fluctuation
- Document distribution of weakness:
- Ocular involvement (ptosis, ophthalmoparesis)
- Bulbar symptoms (nasal voice, dysphagia, dysarthria)
- Limb weakness pattern (proximal vs. distal)
- Respiratory involvement
- Assess fluctuation characteristics:
- Diurnal variation (worse with fatigue/end of day)
- Triggers for worsening (exercise, illness, stress)
- Recovery patterns with rest
Disease Progression
- Document the course of symptoms over time:
- Stability vs. progression of weakness
- Development of new symptoms over time
- Response to previous treatments
- Frequency of respiratory crises or hospitalizations
Family History
- Obtain a detailed three-generation family history 3
- Document consanguinity
- Identify family members with similar symptoms
- Note that parents may be asymptomatic carriers (autosomal recessive inheritance pattern common)
Specific Symptom Assessment
Ocular Symptoms
- Age of onset and progression of ptosis
- Presence of ophthalmoparesis/diplopia
- Compensatory head posture
Bulbar Function
- Feeding difficulties in infancy
- Current swallowing function
- Voice quality (nasal speech)
- History of aspiration pneumonia
Respiratory Function
- History of respiratory crises requiring ventilation
- Sleep-disordered breathing or morning headaches
- Need for ventilatory support (particularly important in DOK7, SCCMS patients) 4
Motor Function and Mobility
- Walking distance limitations (53% of patients have reduced walking distance) 1
- Wheelchair dependency (34% of patients) 1
- Ability to climb stairs, rise from sitting
- Impact on activities of daily living
Treatment History
- Previous treatments and response:
- Acetylcholinesterase inhibitors (pyridostigmine, neostigmine)
- 3,4-diaminopyridine
- Immunosuppressive therapies (if previously misdiagnosed)
- Document dosages and side effects
- Pattern of response to medication (improvement, deterioration, or no change)
Differential Diagnostic Clues
- Negative acetylcholine receptor antibodies (to rule out myasthenia gravis) 2
- Lack of response to immunosuppressive therapy
- Positive family history
- Early age of onset
Important Pitfalls to Avoid
- Misdiagnosis as autoimmune myasthenia gravis - CMS patients are often initially misdiagnosed and inappropriately treated with immunosuppression
- Overlooking subtle bulbar or ocular symptoms - These may not be reported by patients but significantly impact function
- Failure to obtain detailed family history - Essential for genetic diagnosis
- Not recognizing gene-specific phenotypes - Different genetic subtypes have characteristic presentations and treatment responses
Documentation Recommendations
- Create a timeline of symptom onset and progression
- Document all previous treatments and responses
- Record functional limitations in detail
- Note any triggering or alleviating factors
- Document family history with pedigree diagram
The comprehensive history should guide genetic testing and treatment decisions, as different CMS subtypes respond differently to medications. Patients with receptor deficiency mutations (RAPSN, CHRND, CHRNB1) typically have better treatment responses than those with synaptopathy or presynaptic defects 1.