PP09.8 – 2377: Novel DOK7 mutation in a Greek patient with congenital myasthenic syndrome

Abstract

Introduction Congenital myasthenic syndromes (CMS) are rare genetic syndromes resulting from presynaptic, synaptic or postsynaptic defects of the neuromuscular junction. In 2006 mutations in DOK7, a gene encoding a muscle-intrinsic activator of MUSK, were proven a postsynaptic cause of CMS. Until today 65 DOK7 mutations have been described. Case report A 16 year old girl, daughter to healthy, non-consanguineous parents has been followed up at our clinic since birth. History includes decreased fetal movements, hypotonia at birth and slightly delayed motor milestones with sitting at 8 months and walking at 15 months. Neurological examination discloses facial and proximal muscle weakness, bulbar and respiratory weakness, ptosis, joint laxity, massive kyphoscoliosis, feeding difficulty and failure to thrive. The patient is currently ambulant, able to climb stairs and walk approximately 50 meters, before getting tired. Under nocturnal noninvasive ventilation (BiPAP) she maintains oxygen saturation levels >98%. Creatin kinase is 200 U/l (normal: 150 U/l). Electrophysiologic studies revealed normal NCV's and a mildly myopathic EMG. Repetitive nerve stimulation demonstrated mild decrement at infancy, but now is normal. Muscle biopsy showed predominance of type 1 fibers and decreased oxidative activity. Since the clinical features were consistent with CMS, molecular analysis of CHAT, RAPSN, CHRNE and DOK7 was undertaken, which in turn revealed a compound heterozygous mutation in the DOK7 gene. Conclusion To the best of our knowledge this is the first Greek patient with confirmed DOK7 myasthenic syndrome. One of the mutations, the c.472C>T (p.Arg158Trp) has not been previously described. Accurate diagnosis of DOK7 myasthenic syndromes bears important clinical implications, since ephedrine or salbutamol rather than acetylcholinesterase inhibitors are the treatment of choice.