A case of early onset epileptic encephalopathy with de novo mutation in SLC35A2: Clinical features and treatment for epilepsy

Somatic SLC35A2 variants in the brain are associated with intractable neocortical epilepsy

“…This variant was not highlighted in the original report, because mosaic variants at this level in leukocytes had been excluded, but it has since been confirmed to be mosaic and absent in parents (unpublished data). This patient exhibited infantile spasms at age 4 months, developmental delay, and normal MRI, similar to other reported cases with germline SLC35A2 variants . In contrast to the 2 cases with mosaic SLC35A2 variants in brain tissue who presented with epileptic encephalopathy and abnormal MRI, the NLFE cases with mosaic SLC35A2 variants in brain tissue did not present with epileptic encephalopathy or infantile seizure onset.…”

“…This patient exhibited infantile spasms at age 4 months, developmental delay, and normal MRI, similar to other reported cases with germline SLC35A2 variants. 14,[46][47][48] In contrast to the 2 cases with mosaic SLC35A2 variants in brain tissue who presented with epileptic encephalopathy and abnormal MRI, the NLFE cases with mosaic SLC35A2 variants in brain tissue did not present with epileptic encephalopathy or infantile seizure onset.…”

“…Consistent with the presence of SLC35A2 variants localized to brain in our 5 cases, we did not observe any systemic signs of a glycosylation defect, and only one case (Case 4), with the highest burden of mosaic SLC35A2 , has severe intellectual disability. The bilateral MRI white matter abnormalities seen on MRI of this case may, in retrospect, be consistent with a defect in glycosylation that is more widespread in the brain, but of course we do not have data from other brain regions. Our cases represent a wide range of findings, with presence or absence of MRI lesions, pathological findings suggestive of FCD, and associated intellectual disability.…”

SLC35A2‐CDG: Functional characterization, expanded molecular, clinical, and biochemical phenotypes of 30 unreported Individuals

“…The majority of previously reported SLC35A2‐CDG individuals, 27 of 32 (84%; Table S1), were identified by NGS with many of those affected individuals listed in the online supplemental data of large sequencing studies (Bosch et al, ; Bruneel et al, ; Dorre et al, ; Euro, Epilepsy Phenome/Genome, & Epi, ; Kimizu et al, ; Kodera et al, ; Lelieveld et al, ; Ng et al, ; Sim et al, ; Westenfield et al, ; Winawer et al, ; Yates et al, ). This explains why the number of reported subjects cited varies among studies.…”

“…To date, molecular and clinical information on 32 individuals with de novo variants in SLC35A2 have been reported with most exhibiting neurological symptoms, especially epilepsy, developmental delay, and intellectual disability (Bosch et al, ; Bruneel et al, ; Dorre et al, ; Euro, Epilepsy Phenome/Genome, & Epi, ; Kimizu et al, ; Kodera et al, ; Lelieveld et al, ; Ng et al, ; Sim et al, ; Westenfield et al, ; Winawer et al, ; Yates et al, ). Recently, WES analysis of brain specimens from 56 individuals identified five subjects harboring somatic de novo SLC35A2 variants (Winawer et al, ).…”