DOK7 congenital myasthenic syndrome.
Despite being a fairly recent discovery, DOK7 congenital myasthenic syndrome (CMS) is the third most common form of CMS in the United Kingdom. DOK7 is a postsynaptic protein associated with the AChR clustering pathway. In contrast to AChR deficiency due to epsilon subunit mutations, onset of DOK7 CMS tends to be later--ages two to three years--and in DOK7 CMS eye movements are usually spared and anticholinesterases can exacerbate the weakness. The typical phenotype of DOK7 CMS is of a limb girdle weakness with associated nonspecific myopathic features. The presence of stridor in early onset cases and the observation of tongue wasting may be specific clues. Worsening in adulthood is common, particularly affecting bulbar and respiratory function. Treatment with ephedrine or oral salbutamol can result in a slow, steady, and often dramatic improvement over months.