Two families with 5 affected members suffering from congenital myasthenic syndrome are reported from University Hospital, Bonn, Germany. The age at onset of ptosis, extraocular weakness, and exercise intolerance was in childhood or adolescence. The course was slowly progressive. The distribution of muscle weakness was more proximal than distal. All patients had abnormal decremental response on low-frequency 3-Hz nerve stimulation, and no repetitive responses to single nerve shock. All improved with anti-acetylcholinesterase drugs. Intercostal muscle biopsies from one patient in each family showed type 1 fiber predominance, and marked reduction in number of secondary synaptic clefts per neuromuscular junction and in the expansion of the postsynaptic area. Acetylcholine-receptor (AChR) density was reduced, and AChR-associated protein utrophin was deficient in the end-plate, on immunohistochemical analysis. Both patients showed a defect in the development or maintenance of the postsynaptic clefts. [1]

COMMENT. Since the clinical description of a congenital myasthenic syndrome [2], as distinguished from the neonatal transient form, several congenital myasthenic syndromes have been identified. Engel AG et al at the Mayo Clinic have reported patients and families with endplate acetylcholine and AChR deficencies, a slow-channel syndrome, defects in resynthesis of ACh and kinetics of AChR, and abnormal interaction of acethylcholine with its receptor. (see Progress in Pediatric Neurology III, 1997;pp346-347, for reviews of Mayo Clinic reports).

The Bonn families with congenital myasthenic syndrome had defects in the postsynaptic clefts with deficiencies in end-plate acetylcholine receptor and utrophin (dystrophin-related protein). The authors note that their patients resemble reports of a so-called congenital paucity of secondary synaptic clefts syndrome (CPSC) (Smit et al. 1988; Wokke et al. 1989). These familial syndromes have different clinical features and absent anti-AChR antibodies that distinguish them from autoimmune myasthenia gravis.