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Título

Molecular characterization of congenital myasthenic syndromes in reference outpatient clinic, in Salvador, Bahia

RESUMO

CASE PRESENTATION: JGL, fem., 6y, frequent falls since 2y, evolved with difficulty to walk and to stand up. MS 4/5 distal and 3/5 proximal, axial hypotonia and areflexia. Gait with adducted feet and tendency to fall. Genetic testing (GT): DOK7 gene mutation. Improvement with Albuterol. RSS, fem., 47y, ptosis, diplopia, fluctuating weakness of distal and cervical predominance. EMG: mild neuromuscular junction (NMJ) disorder. GT: mutation in the CHRND, DOK7 and COL1 genes. Improvement with Albuterol and Fluoxetine. AJS, fem., 36y, weakness in both LL with frequent falls since birth. Between 11-27y used an unremembered medication with improvement. At 27y, evolved with fluctuating weakness in both UL, cramps and fasciculations after cesarean section. MS 2/5 proximal and 4/5 distal. EMG: decremental pattern and postsynaptic impairment of NMJ. Reduced vital capacity. GT: mutation in the DOK7 gene. Improvement with Albuterol and Fluoxetine. JMS, fem., 34y, fatiguing global weakness, bilateral ptosis and NPMD delay since birth. Consanguineous parents and three family generations with intellectual deficit and epilepsy. Presents facial dysmorphia, bilateral semiptosis, paresis of VI CN, MS 3/5 proximal and 4/5 distal. EMG: postsynaptic involvement of JNM. Suspected of congenital myasthenia (CM), with improvement with Albuterol but not Mestinom. GT: mutation in the CHRNE gene. DISCUSSION: CM is a rare and difficult to diagnose entity usually seen in childhood, but may be insidious/present late. Common symptoms include fluctuating muscle weakness, bulbar symptoms, ophthalmoparesis and ptosis. The most common associated gene mutations are: CHRN, DOK7, RAPSN. CHRN encodes the subunits of the ACh receptor and the mutation deforms it, being able to cause two separate syndromes depending on the affected subunit, as seen in RSS’s and JMS’s cases. DOK7 is an adaptive protein bound to MuSK. Its mutation can affect breathing since birth and cause weakness and ptosis throughout life. There is marked improvement with Albuterol or Ephedrine, as seen in the cases. FINAL COMMENTS: Despite rare, CM should be suspected when the clinical history and therapeutic response isn’t similar to the usual response for Myasthenia Gravis. Genetic testing helps to guide the treatment and dictate the prognosis, modifying the quality and lifestyle of the patient and their relatives. It also helps to identify the most common mutated genes and new mutations that can contribute to future diagnoses.