RESUMO
The spectrum of RYR1 mutation associated disease encompasses congenital myopathies, exercise induced rhabdomyolysis, malignant hyperthermia susceptibility and King-Denborough syndrome. We report the clinical phenotype of two siblings who presented in infancy with hypotonia and striking fatigable ptosis. Their response to pyridostigimine was striking, but genetic screening for congenital myasthenic syndromes was negative, prompting further evaluation. Muscle MRI was abnormal with a selective pattern of involvement evocative of RYR1-related myopathy. This directed sequencing of the RYR1 gene, which revealed two heterozygous c.6721C>T (p.Arg2241X) nonsense mutations and novel c.8888T>C (p.Leu2963Pro) mutations in both siblings. These cases broaden the RYR1-related disease spectrum to include a myasthenic-like phenotype, including partial response to pyridostigimine. RYR1-related myopathy should be considered in the presence of fatigable weakness especially if muscle imaging demonstrates structural abnormalities. Single fibre electromyography can also be helpful in cases like this.
Assuntos
Inibidores da Colinesterase/uso terapêutico , Miotonia Congênita/tratamento farmacológico , Miotonia Congênita/genética , Brometo de Piridostigmina/uso terapêutico , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Biópsia , Códon sem Sentido , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Fadiga Muscular/efeitos dos fármacos , Fadiga Muscular/fisiologia , Músculos/efeitos dos fármacos , Músculos/patologia , Músculos/fisiopatologia , Miotonia Congênita/patologia , Miotonia Congênita/fisiopatologia , Irmãos , Resultado do TratamentoRESUMO
Phospholipase A2 associated neurodegeneration (PLAN) is a major phenotype of autosomal recessive Neurodegeneration with Brain Iron Accumulation (NBIA). We describe the clinical phenotypes, neuroimaging features and PLA2G6 mutations in 5 children, of whom 4 presented with infantile neuroaxonal dystrophy (INAD). One other patient was diagnosed with the onset of PLAN in childhood, and our report highlights the diagnostic challenges associated with this atypical PLAN subtype. In this series, the neuroradiological relevance of classical PLAN features as well as apparent claval hypertrophy' is explored. Novel PLA2G6 mutations were identified in all patients. PLAN should be considered not only in patients presenting with a classic INAD phenotype but also in older patients presenting later in childhood with non-specific progressive neurological features including social communication difficulties, gait disturbance, dyspraxia, neuropsychiatric symptoms and extrapyramidal motor features.
