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Título

MUSK-related Congenital Myasthenic Syndrome: First report of adult-onset case in Brazil

RESUMO

CASE REPORT: A 33-year-old man presented with severe muscular fatigue for more than a year, more pronounced in the evening, associated with double vision and eyelid ptosis, both initially intermittent, then continuous after six months.

Neurologic examination revealed dysphonia, bilateral eyelid ptosis with fatigue during maneuvers, discrete global ophthalmoparesis, bilateral facial nerve palsy, and discrete and symmetric palatal numbness. MRC muscle strength was 4/5 in the proximal lower and upper limbs and global hyporeflexia.

Needle EMG showed a myopathic pattern and a deltoid muscle biopsy revealed nonspecific mild and chronic myopathic findings. Initially, we tried pyridostigmine and prednisone. LF-RNS showed a pathological decrement of 18%. His condition progressively worsened until he suffered six episodes of myasthenic crisis within a year, requiring prolonged mechanical ventilation, IGIV, PLEX, and remained refractory even with rituximab. Both anti-AchR and anti-MUSK were negative.

His 29-year-old sister had a history of eyelid ptosis, neonatal hypotonia, and an isolated episode of GTC seizure associated with hypoxia. At age 22, she began to experience intense and slowly progressive muscular fatigue, particularly in the lower limbs, associated with eyelid ptosis. Neurologic examination revealed appendicular fatigue, eyelid ptosis, and discrete ophthalmoparesis without dysphonia or dysphagia.

Genetic testing on both siblings confirmed the diagnosis of MUSK-related autosomal recessive congenital myasthenic syndrome. NGS-based gene panel testing disclosed the presence of compound heterozygous variants c.2125G>A (p.Val709Met) and a deletion of exons 3-4 in the MUSK gene.

DISCUSSION: Congenital myasthenic syndrome (CMS) is a clinic and genetically heterogeneous group of inherited neuromuscular disorders, which share impaired neuromuscular transmission due to distinct genetic mechanisms. Autosomal recessive pattern of inheritance is observed in the MUSK (9q31.3) gene-related CMS. MUSK encodes a post–synaptic protein involved in endplate maintenance and maturation, proper function of Rapsyn and AchR, thus acting in the AchR clustering pathway. Treatment of CMS is not standardized because of the small number of patients and the lack of specific therapeutic trials.

CONCLUSION: Our cases expand the current knowledge about CMS and provide original information regarding the first genetically confirmed adult-onset MUSK-related CMS case in Brazilian population.

Palavras Chave

MUSK gene, congenital myasthenic syndrome, neuromuscular transmission, fatigability, muscle weakness