Congenital myasthenic syndrome (CMS) with end-plate acetylcholinesterase (AChE) deficiency is a rare autosomal recessive disease, recently classified as CMS type Ic (CMS-Ic). It is characterized by onset in childhood, generalized weakness increased by exertion, refractoriness to anticholinesterase drugs, and morphological abnormalities of the neuromuscular junctions (NMJs). The collagen-tailed form of AChE, which is normally concentrated at NMJs, is composed of catalytic tetramers associated with a specific collagen, COLQ. In CMS-Ic patients, these collagen-tailed forms are often absent. We studied a large family comprising 11 siblings, 6 of whom are affected by a mild form of CMS-Ic. The muscles of the patients contained collagen-tailed AChE. We first excluded the ACHE gene (7q22) as potential culprit, by linkage analysis; then we mapped COLQ to chromosome 3p24.2. By analyzing 3p24.2 markers located close to the gene, we found that the six affected patients were homozygous for an interval of 14 cM between D3S1597 and D3S2338. We determined the COLQ coding sequence and found that the patients present a homozygous missense mutation, Y431S, in the conserved C-terminal domain of COLQ. This mutation is thought to disturb the attachment of collagen-tailed AChE to the NMJ, thus constituting the first genetic defect causing CMS-Ic.

The three volumes (38, 28, and 20 ml) of mepivacaine 10 mg x ml(-1) ensured a similar and high percentage of complete sensory blocks in axillary brachial plexus anaesthesia with nerve stimulation involving the location of four motor responses.

This pilot study indicates that the cuff method could be useful to monitor neuromuscular blockade according to the bias and limits of agreement compared with MMG, particularly when the degree of blockade was evaluated by TOF ratios > 0.7. The new cuff method is easy and simple to use. However, further studies in a larger number of patients are necessary to confirm these favourable preliminary results.

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