A novel <i>SLC1A4</i> homozygous mutation causing congenital microcephaly, epileptic encephalopathy and spastic tetraparesis: a video-EEG and tractography – case study

Biallelic mutations in the <i>SLC1A4</i> gene have been identified as a very rare cause of neurodevelopmental disorders. l-serine transport deficiency has been regarded as the causal molecular mechanism underlying the neurological phenotype of <i>SLC1A4</i> mutation patients. To date this genetic condition has been reported almost exclusively in a limited number of Ashkenazi-Jewish individuals and as a result the <i>SLC1A4</i> gene is not routinely included in the majority of the genetic diagnostic panels for neurological diseases. We hereby report a 7-year-old boy from a Southern Italian family, presenting with epileptic encephalopathy, congenital microcephaly, global developmental delay, severe hypotonia, spasticity predominant at the lower limbs, and thin corpus callosum. Whole exome sequencing identified a novel segregating <i>SLC1A4</i> gene homozygous mutation (c.1141G &gt; A: p.Gly381Arg) as the likely cause of the disease in our family. In order to deeply characterize the electro-clinical and neurological phenotype in our index patient, long-term systematic video-electroencephalograms (EEG) as well as repeated brain imaging studies (which included tractographic reconstructions) were performed on a regular basis during a 7 years follow-up time. In conclusion, we suggest to carefully considering <i>SLC1A4</i> biallelic mutations in individuals presenting an early onset severe neurodevelopmental disorder with variable spasticity and seizures, regardless the patients’ ethnic background.