Table 2.

Diagnostic clues in congenital myasthenic syndromes Generic diagnosis

Generic diagnosis Fatigable weakness involving ocular, bulbar and limb muscles since infancy or early childhood Similarly affected relative Decremental EMG response at 2- to 3-Hz stimulation Negative tests for anti-AChR antibodies, MuSK, and P/Q type calcium channels

Exceptions and caveats In some CMS the onset is delayed45,37 There may be no similarly affected relatives The symptoms can be episodic7,13,44 EMG abnormalities may not be present in all muscles, or are present only intermittently7,13 Weakness may not involve cranial muscles40

Clinical clues pointing to a specific diagnosis*

Endplate AChE deficiency 35 Repetitive CMAPs Refractoriness to cholinesterase inhibitors Delayed pupillary light reflexes

Slow-channel CMS45 Repetitive Compound Muscle Fiber Action Potential (CMAPs) Selectively severe involvement of cervical and wrist and finger extensor muscles in most cases Dominant inheritance in most cases

Endplate choline acetyltransferase deficiency7,46 Recurrent apneic episodes, spontaneous or with fever, vomiting, or excitement No or variable myasthenic symptoms between acute episodes Stimulation at 10 Hz for 5 min causes marked decrease of CMAP followed by slow recovery EMG decrement at 2 Hz can be absent at rest but appears after stimulation at 10 Hz for 5 min, then disappears slowly.

Rapsyn deficiency Multiple congenital joint contractures in one-fourth of patients Increased weakness and respiratory insufficiency precipitated by intercurrent infections EMG decrement can be mild or absent.

Dok-7 myasthenia 40,15 Proximal greater than distal limb and axial muscle weakness, mild facial weakness and ptosis, and normal ocular ductions in the majority Bulbar muscles affected in some patients May deteriorate on exposure to pyridostigmine

^*There are no clinical clues to the diagnosis of the fast channel CMS, primary EP AChR deficiency, and most cases of rapsyn deficiency.

Abbreviations: AChE, acetylcholinesterase; AChR, acetylcholine receptor; CMAP, compound muscle fiber action potential; EMG. electromyogram; EP, endplate.