1 - Child Neurology Unit, Pediatrics Department, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central, Lisboa
2 - Neurorradiology Department, Centro Hospitalar Universitário Lisboa Central, Lisboa
3 - Rehabilitation Department, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central, Lisboa
- Reunião internacional - 14th European Paediatric Neurology Society Congress
Objective: The investigation of a complex neurological phenotype may mask the suspicion of a congenital myasthenic syndrome.
Methods: Case report
Results: Ten-year-old girl, with no relevant family or gestational history, who presented at the age of 17 months with developmental delay, global hypotonia, hyperlaxity and slight right hemiparesis. She acquired gait at 25 months and had language development delay. Brain MRI revealed multifocal white matter changes and reduced volume of the right corticospinal tract on tractography. CMV PCR on neonatal blood was negative. There was a slight elevation of creatine kinase. From the age of 3 years, parents noticed tiredness, falls, difficulty in controlling her head and dysphagia that soon appeared fluctuating along the day and from day to day. In the following years, limb girdle weakness became apparent. The first EMG (38 months) raised the suspicion of myopathy. Muscle biopsy and mitochondrial respiratory chain studies were inconclusive. At 49 months, however, arepeat EMG found decrement on repetitive stimulation. The NGS gene panel for congenital myasthenic syndromes subsequentlyfound 2 variants of undetermined significance on DPAGT1 gene in compound heterozygoty. Transferrin isoelectric focusing was altered, confirming the pathogenicity of these variants, and confirming the double diagnosis of congenital myasthenic syndrome and congenital disorder of glycosylation. Currently, the patient presents a developmental language and motor coordination disorder, slight bilateral facial palsy, nasal dysphonia, global hypotonia, hyperlaxity and limb girdle weakness and is treated with ephedrine with favourable response.
Conclusions: This case illustrates how the availability of genetic diagnosis is blurring the distinction between central and peripheral nervous system pathology for complex phenotypes. The key for this diagnosis was the development of fluctuation of clinical weakness.
Palavras Chave: congenital myasthenic syndrome, congenital disorder of glycosylation, DPAGT1 gene