A novel mutation in sphingosine-1-phosphate lyase causing congenital brain malformation

Introduction: Recently recessive mutations in sphingosine-l-phosphate lyase (SGPLI) have been published as a cause of syndromic congenital nephrotic syndrome with adrenal insufficiency. We have identified a case with fetal hydrops and brain malformations due to a mutation in SGPLI. Case report: We report a patient presenting with severe fetal hydrops, congenital nephrotic syndrome and adrenal calcifications. MRI imaging showed generalized cortical atrophy with simplified gyral pattern and hypoplastic temporal lobes as well as cerebellar hypoplasia and hyperintensity in the pons. The boy deceased at 6 weeks of age. Via whole exome sequencing, we identified a novel homozygous frameshift mutation c.1233delC (p.Phe4llLeufs*56) in SGPLI. Conclusion: In our patient, we describe a novel mutation in sphingosine-1-phosphate lyase (SGPLI) leading to severe brain malformation. Neurodevelopmental phenotypes have been reported earlier, but not described in detail. To this end, we present a review on all published SGPLI-mutations and genotype-phenotype correlations focusing on neurodevelopmental outcomes. We hypothesized on the severe neurological phenotypes, which might be due to disruption of neuronal autophagy. Mutations in SGPLI shall be considered in the differential diagnosis of fetal hydrops as well as congenital brain malformations and neuropathies. (C) 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.