Two novel slow-channel congenital myasthenic syndromes (SCCMS) with mutations in the AChR e subunit are reported from the John Radcliffe Hospital, Oxford, UK. In two of three kinships, the syndrome showed an atypical recessive inheritance pattern. Typically SCCMS has a dominant inheritance. In Pedigree 1, the index patient presented at 29 years of age with failure to breathe after a general anesthetic. Her parents were consanguineous. Examination revealed bilateral ptosis, weakness of eye closure, facial muscles, shoulder, hand and hips. In Pedigree 2, the index patient developed ptosis at 17 years, and weakness progressed to other muscle groups over the next 7 years. Pedigree 3 index patient noted transient weakness of finger extensors in her twenties, which later progressed to mild involvement of wrist, neck and other muscles. Antibodies to AChR were absent in all three patients and there was no response to anticholinesterase treatment. EMG showed decrement of the CMAP and a repetitive response to a single nerve stimulus. Only Pedigree 3 showed a typical dominant inheritance pattern. [1]

COMMENT. Slow-channel congenital myasthenic syndromes are typically of dominant inheritance and caused by missense mutations in the muscle nicotinic acetylcholine receptor (AChR). Symptoms are present at birth or may be delayed until adulthood. Fatigable muscle weakness, selectively involving neck, shoulder and finger extensors, is mild or severe and tends to be slowly progressive. Response to anticholinesterase treatment is absent, and EMG shows a double response to a single nerve stimulus. Adding to the 11 previously described mutations underlying the SCCMS, the Oxford team describes two new mutations in the e subunit, with symptoms present only in the index patient, and the first reported examples of recessively inherited SCCMS.