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The congenital myasthenia syndromes (CMS) are a group of autosomal recessive or autosomal dominant diseases that affect neuromuscular junctions. CMS caused by AGRN mutations is very uncommon typically characterized by ptosis, mild weakness, and proximal limb weakness. We report the case of an 8-year-old female who exhibited the onset of motor development retardation from infancy and slow progression to proximal muscle weakness. Repeated nerve stimulation at 3 Hz showed a clear decrement with 17%. Whole exon sequencing showed an AGRN gene compound heterozygous mutation (c.5009C >T and c.5078T > C). She was treated with salbutamol but without improvement. Then pseudoephedrine was adapted as a treatment choice and obtained remarkable curative effect. We have summarized and analyzed 12 patients who have been reported in the literature. An early age of onset and muscle weakness in the lower limbs are the main feature of an early AGRN gene mutation. Both types of AGRN-related CMS respond favorably to ephedrine. This is the first report showing that pseudoephedrine is effective as a choice for the treatment of AGRN-related CMS.

Background The ARHGEF9 gene variants have phenotypic heterogeneity, the number of reported clinical cases are limited and the genotype–phenotype relationship is still unpredictable. Methods Clinical data of the patients and their family members were gathered in a retrospective study. The exome sequencing that was performed on peripheral blood samples was applied for genetic analysis. We used the ARHGEF9 gene as a key word to search the PubMed database for cases of ARHGEF9 gene variants that have previously been reported and summarized the reported ARHGEF9 gene variant sites, their corresponding clinical phenotypes, and effective treatment. Results We described five patients with developmental and epileptic encephalopathy caused by ARHGEF9 gene variants. Among them, the antiepileptic treatment of valproic acid and levetiracetam was effective in two cases individually. The exome sequencing results showed five children with point mutations in the ARHGEF9 gene: p.R365H, p.M388V, p.D213E, and p.R63H. So far, a total of 40 children with ARHGEF9 gene variants have been reported. Their main clinical phenotypes include developmental delay, epilepsy, epileptic encephalopathy, and autism spectrum disorders. The variants reported in the literature, including 22 de novo variants, nine maternal variants, and one unknown variant. There were 20 variants associated with epileptic phenotypes, of which six variants are effective for valproic acid treatment. Conclusion The genotypes and phenotypes of ARHGEF9 gene variants represent a wide spectrum, and the clinical phenotype of epilepsy is often refractory and the prognosis is poor. The p.R365H, p.M388V, p.D213E, and p.R63H variants have not been reported in the current literature, and our study has expanded the genotype spectrum of ARHGEF9 gene. Our findings indicate that levetiracetam and valproic acid can effectively control seizures in children with epileptic phenotype caused by ARGHEF9 gene variations. These findings will help clinicians improve the level of diagnosis and treatment of the genetic disease.