CONGENITAL MYASTHENIC SYNDROMES AND MYASTHENIA: P.74Five years of salbutamol treatment in a girl with congenital myasthenic syndrome caused by mutations in COL13A1

Abstract

The beneficial effect of salbutamol has been demonstrated in an icreasing number of congenital myasthenic syndromes (CMS). We present a 22 year-old girl who presented at birth with signs of CMS. She was born from consanguineous parents, whose two-year-old first son had been previously diagnosed with a syndrome of congenital insensitivity to pain with anhidrosis, due to a homozygous mutation in the NTRK1 gene (c.C2011T, p.R643W). Prenatal screening showed that the female fetus carried the mutation in heterozygosity. The patient presented at birth with hypotonia, ptosis, severe respiratory insufficiency and swallowing dysfunction, that required tracheostomy and gastrostomy. Physical examination evidenced dysmorphic features including retrognathia, high-arched palate, and pectus carinatum. EMG identified a myasthenic pattern of muscle activation and treatment was started with piridostigmine and 3,4-diaminopyridine with some improvement. Tracheostomy could be removed at 4 years of age and switched to non-invasive ventilation. During the following years, the patient presented severe episodes of acute respiratory insufficiency that required multiple hospitalizations. Extensive genetic analysis failed to identify the cause of the CMS. Five years ago, treatment was started with oral salbutamol and the patient presented a clear improvement in respiratory funtion and the respiratory crisis completely dissapear. Sequencing of the COL13A1 gene identified a homozygous mutation c.648C>G (p.Tyr216*). Even without diagnosis, treatment with salbutamol could be worth trying when other therapies were unsuccessful.