engleski

Rare mutation of Congenital Myasthenic Syndrome

Congenital myasthenic syndromes are group of neuromuscular junction disorders. The most common classification of CMS relies on the location of the mutated protein, in presynaptic, synaptic basal lamina or postsynaptic components of the neuromuscular junction. Prevalence of genetically confirmed cases is approximately 9, 2 per million. The syndromes share some of the clinical features like fatigable weakness but are heterogeneous considering age of onset, distribution of weakness, response to therapy because of the underlying genetic defect. We are presenting a boy , age 14, with generalized fatigable weakness that worsens during the day and has become more prominent for the past 2 years. He was born from uneventful pregnancy but presented in infancy with feeding difficulties, hypotonia and prolonged, recurrent respiratory infections. He started walking at the age of 18 months and developed a slurred speech that needed a logopedic therapy. He had eyelid ptosis since birth. Because of the scoliosis he went to psychiatric examination and was referred to neuropediatrics. His laboratory findings including CK and antibodies against AchR i MUSK were normal, but EMNG findings considering repetitive stimulation was positive. He was referred to genetic testing – Neuromuscular Disorders Panel. We got positive result – pathogenic variant identified in CHRD gene responsible for CHRND protein function. Up to date, 32 gene mutations are reported in CMS, CHRND represented in 1% of all mutations so far. CHRND protein is one of five subunits of acetilcholin receptor and by that a mutation of CHRND gene is responsible for AchR malfunction but can also affect the kinetics of AchR leading to prolonged (slow channel syndrome, SCS) or brief openings (fast channel syndrome, FCS). Our patient had clinical features that mostly resembled SCS phenotype, but had his first symptoms in infancy which is not the case in SCS. On the basis of described cases so far, patients can be treated with 3, 4-DAP and pyridostigmin, but if our patient had SCS there could be a deterioration of clinical manifestations if treated with pyridostigmin. Because of that, we have done a pyridostgmin test that was positive and he started the therapy with pyridostigmin.

congenital myasthenic syndrome ; mutation

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