VAMP1-Related Congenital Myasthenic Syndrome: A Case Report and Literature Review.

Congenital myasthenic syndrome-25 (CMS-25) is an autosomal recessive neuromuscular disorder caused by a homozygous mutation in VAMP1 gene. To date, only eight types of allelic variants in VAMP1 gene have been reported in 12 cases of CMS-25. Here, we report on an 8-year-old boy with motor developmental delay, axial hypotonia, myopathic face, muscle weakness, strabismus, ptosis, pectus carinatum, kyphoscoliosis, joint contractures, joint laxity, seizures, and recurrent nephrolithiasis. He also had feeding difficulties and recurrent aspiration pneumonia. Brain magnetic resonance imaging at 20 months of age showed left focal cerebellar hypoplasia. Genetic analysis revealed a homozygous missense variant of c.202C > T (p.Arg68Ter) in the VAMP1 gene. Treatment with oral pyridostigmine was started, which resulted in mild improvement in muscle strength. Salbutamol syrup was added a few months later, but no significant improvement was observed. This case report presents novel findings such as focal cerebellar hypoplasia and nephrolithiasis in VAMP1-related CMS-25. Consequently, this case report extends the clinical spectrum. Further studies are needed to expand the genotype-phenotype correlations in VAMP1-related CMS-25.

Hypomelanosis of Ito presenting with unilateral dilation of Virchow-Robin spaces: a case report.

Hypomelanosis of Ito is a rare heterogeneous neurocutaneous disorder often associated with central nervous and musculoskeletal system involvement. Herein, we report the first case of hypomelanosis of Ito in the literature presenting with unilateral dilation of Virchow-Robin spaces (VRS). A girl aged 16 years old presented with a 1-year history of headache. Her physical and neurological examinations were normal, except for the presence of unilateral cutaneous macular hypopigmented whorls and streaks on lower side of the right trunk and lower limb, termed as Blaschko's lines. She had mild deficits in cognitive and adaptive functioning. Hearing, renal, dental, ophthalmologic, metabolic, and cardiac assessments were normal. Brain magnetic resonance imaging (MRI) showed markedly unilateral hemispheric enlarged VRS without contrast enhancement and diffusion restriction. To the best of our knowledge, our case is the first report describing the unilateral hemispheric enlarged VRS in a patient with hypomelanosis of Ito. Our report suggested that hypomelanosis of Ito may have unilateral dilation of VRS in brain MRI.

Ketogenic diet-responsive drug-resistant epilepsy in a case of asparagine synthetase deficiency with a novel compound heterozygous missense variant.

Asparagine synthetase deficiency (ASNSD) is a rare autosomal recessive neurometabolic disorder caused by homozygous or compound heterozygous mutations in the ASNS gene. Most of the patients have early-onset intractable seizures. A 7-year-old boy was first admitted to our clinic with intractable febrile and afebrile seizures that started when he was 6 months old. He had axial hypotonia with spastic quadriparesis, mild facial dysmorphism, and acquired microcephaly at 1 year-old. Metabolic tests showed a borderline-low serum asparagine level. The electroencephalogram demonstrated epileptic discharges with a high incidence of multifocal spike-wave activity. Brain MRI showed mild cerebral atrophy. His seizures continued despite combinations of multiple antiseizure agents. Whole-exome sequencing (WES) revealed a novel compound heterozygous missense variant of the ASNS gene, and the variants were confirmed by Sanger sequencing. He was started on a ketogenic diet at five years and six months of age. In the first month of the ketogenic diet, we observed that the frequency of seizures significantly decreased. He showed a remarkable improvement in seizures and milder improvement in cognitive skills. To our knowledge, our case is the first report describing significant improvement with a ketogenic diet in intractable seizures due to ASNSD.