L1 syndrome, a complex X-linked neurological disorder, is caused by mutations in the L1 cell adhesion molecule (L1CAM) gene. L1CAM molecule is a member of immunoglobulin (Ig) superfamily of neural cell adhesion molecules (CAMs), which plays a pivotal role in the developing nervous system. In this study, a L1CAM gene exonic missense variant (c.1108G > A, p.G370R) was identified in two induced fetuses (abnormal fetuses), who presented corpus callosum agenesis accompanied with hydrocephalus. Clinical data, published literature, online database, and bioinformatic analysis suggest that the single-nucleotide variant of L1CAM gene is a likely pathogenic mutation. In vitro assays were performed to evaluate the effects of this variant. Based on NSC-34/COS-7 cells transfected with wild-type (L1-WT) and mutated (L1-G370R) plasmids, the L1CAM gene exonic missense variant (c.1108G > A, p.G370R) reduced cell surface expression, induced partial endoplasmic reticulum retention, affected posttranslational modification, and reduced protein's homophilic adhesive ability, but did not induce endoplasmic reticulum stress, which might probably associate with L1 syndrome. Finally, 35 isolated fetuses were screened for L1CAM gene variants by Sanger sequencing. These cases all prenatally suspected of corpus callosum agenesis accompanied with hydrocephalus, which may relate to L1 syndrome. Consequently, one L1CAM gene single missense variant (c.550C > T, p.R184W) was detected in one fetus. Our results provided evidence that the L1CAM gene missense variant (c.1108G > A, p.G370R) may relate to L1 syndrome. The findings of this study suggest a potential possibility of L1CAM gene screening for prenatal diagnoses for fetuses presented corpus callosum agenesis accompanied with hydrocephalus.

The term "cerebral palsy mimic" is used to describe a number of neurogenetic disorders that may present with motor symptoms in early childhood, resulting in a misdiagnosis of cerebral palsy. Cerebral palsy describes a heterogeneous group of neurodevelopmental disorders characterized by onset in infancy or early childhood of motor symptoms (including hypotonia, spasticity, dystonia, and chorea), often accompanied by developmental delay. The primary etiology of a cerebral palsy syndrome should always be identified if possible. This is particularly important in the case of genetic or metabolic disorders that have specific disease-modifying treatment. In this article, we discuss clinical features that should alert the clinician to the possibility of a cerebral palsy mimic, provide a practical framework for selecting and interpreting neuroimaging, biochemical, and genetic investigations, and highlight selected conditions that may present with predominant spasticity, dystonia/chorea, and ataxia. Making a precise diagnosis of a genetic disorder has important implications for treatment, and for advising the family regarding prognosis and genetic counseling. © 2019 International Parkinson and Movement Disorder Society.