PMC6657212_01
(A) The patient's family pedigree. The chart is significant for consanguinity and a similar phenotype observed in several family members. Arrow points to the affected patient. (B) Sanger sequencing for SLC16A1 mutation analysis. The patient is homozygous for SLC16A1 c.218delG in Exon 3. Heterozygosity for c.218delG in Exon 3 of the SLC16A1 gene is displayed in the parents and sibling (brother). The Reverse Primer was used in the analysis. The colors represent bases: green denotes A, red T, black G, and blue C. Forward Primer, GAGGGAGCAGTTTCCTTTATATT; reverse primer, CTCACCTCCAATGACTCCAA.
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F1
Following the exclusion of metabolic disorders, and due to the significant family history for consanguinity in the parents (first-degree cousins) and a similar phenotype seen in two different generations in the maternal family (Figure 1A), genetic analysis in the family was recommended. The patient has been shown to be homozygous for the c.218delG pathogenic variant in the SLC16A1 Gene (p.Gly73ValfsX8 in exon 3 in the SLC16A1 gene, rs1553208520) (Figure 1B). The patient's mother and father are heterozygous carriers for the c.218delG variant in the SLC16A1 Gene (Figure 1B).
MRI Brain. Bilateral symmetrical abnormal T2/FLAIR hyperintense white matter signal changes with diffusion restriction are seen mainly involving the superficial subcortical U fibers with an anterior pre-dominance and involvement of the subinsular white matter. The corpus callosum, thalami, and basal ganglia are also involved. (A) Axial T2W1, (B) Coronal T2W1, (C) Axial DW1, and (D) Axial T1W1. Red arrows points to heterotopia on T1W1.
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F2
MRI was performed at the age of 18 months. MRI showed bilateral symmetrical abnormal T2/Fluid attenuated inversion recovery (FLAIR) hyperintense cortical/subcortical white matter signal involving the superficial subcortical U fibers of the frontal lobes, sub insular white matter, and the anterior temporal, parietal, and occipital lobes with corresponding significant diffusion restriction on Diffusion-weighted magnetic resonance imaging (DWI) (Figures 2A-D). In addition, multiple bilateral gray matter heterotopias were noted involving the posterior horns and trigones of the lateral ventricles bilaterally (Figures 2A-D).