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Focal segmental glomerulosclerosis (FSGS) is an etiologically heterogeneous disorder. Genetic FSGS may be either limited to the kidney or part of a genetic syndrome with other systemic involvement. At least 21 and 34 genes have been reported for renal-limited and syndromic FSGS, respectively. The TRIM8 gene encodes a tripartite motif protein, which is an E3 ubiquitin-protein ligase that promotes proteasomal degradation of the suppressor of cytokine signaling 1 (SOCS1) and participates in the activation of interferon-gamma signaling. The TRIM8 gene is expressed in various tissues including the kidney and the central nervous system (CNS). An association between a mutation in the TRIM8 gene and childhood-onset FSGS has not been well established. We describe an 8-year-old Hispanic male with infantile onset motor and developmental delay, seizures, and proteinuria secondary to FSGS. Next generation sequencing revealed a heterozygous de novo pathogenic variant in the TRIM8 gene (C1380T>A, p.Tyr460*). Immunohistochemical staining using anti-TRIM8 and anti-SOCS1 antibodies showed no significant TRIM8 expression and strong expression of SOCS1 in the renal biopsy tissue. De novo truncating mutations of TRIM8 have been previously reported in childhood-onset epileptic encephalopathy. A molecular analysis of TRIM8 should be considered in children with FSGS and clinical abnormalities of the central nervous system.

Pathogenic de novo variants in the X-linked gene SLC35A2 encoding the major Golgi-localized UDP-galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder of glycosylation known as SLC35A2-congenital disorders of glycosylation (CDG; formerly CDG-IIm). To date, 29 unique de novo variants from 32 unrelated individuals have been described in the literature. The majority of affected individuals are primarily characterized by varying degrees of neurological impairments with or without skeletal abnormalities. Surprisingly, most affected individuals do not show abnormalities in serum transferrin N-glycosylation, a common biomarker for most types of CDG. Here we present data characterizing 30 individuals and add 26 new variants, the single largest study involving SLC35A2-CDG. The great majority of these individuals had normal transferrin glycosylation. In addition, expanding the molecular and clinical spectrum of this rare disorder, we developed a robust and reliable biochemical assay to assess SLC35A2-dependent UDP-galactose transport activity in primary fibroblasts. Finally, we show that transport activity is directly correlated to the ratio of wild-type to mutant alleles in fibroblasts from affected individuals.

Pediatric stroke is particularly challenging because of its variable presentation and relative rarity. Diagnosis of pediatric stroke is often delayed while other diagnoses are considered, unfortunately leading to a loss of therapeutic opportunity. Recent research advances in adult stroke such as multimodal imaging and a clinical trial showing benefits in extending the therapeutic window for thrombolytics are likely to have important implications in pediatric stroke. We describe the case of a 13-year-old boy presenting with acute stroke where multimodal magnetic resonance imaging with perfusion and permeability images allowed safe treatment with thrombolysis outside the standard treatment time window.

The benefits of hemicraniectomy for malignant middle cerebral artery (MCA) stroke may not be apparent in the 3 to 6 months in which final outcomes are assessed in research studies. We present the case of a 15 year-old who underwent hemicraniectomy for malignant MCA stroke and was significantly disabled 3 and 6 months after event. Over the long-term she was able to graduate from university, play tennis, and live an independent life. Although functional independence with only minor disability is relatively rare in adult hemicraniectomy patients, this outcome may be more easily achieved in children during a longer period of follow-up.

Studies have suggested disparate variables affecting long-term outcomes in patients with infantile spasms. Using a retrospective chart review, the authors identified 109 patients who had follow-up data for at least 1 year since the onset of spasms. Patient and treatment variables were recorded, in addition to neurodevelopmental and seizure outcomes. Etiology was strongly associated with motor and cognitive status but not with long-term seizure control. Lag time to initiation of treatment was not predictive of any outcome, nor for need to use a second agent to resolve spasms, even when controlling for etiology. However, patients who responded to the first medication achieved superior seizure and cognitive outcomes. The delayed impact of individual medications could not be analyzed because many patients received multiple agents. While etiology and response to first medication predict better outcomes, the majority of patients with infantile spasms continue to have epilepsy with long-term motor and cognitive disabilities.

Botulinum toxins are potent neurotoxins used in a variety of neurological disorders. Few pediatric reports have been published to date regarding the potential hazards of therapeutic use of botulinum toxins. We describe the case of a 10-year-old boy who developed systemic weakness following treatment of spasticity with botulinum toxin type B. The patient developed iatrogenic botulism with ptosis, facial diplegia, neck flexor and extensor weakness, and profound hypopharyngeal laxity with respiratory compromise from which he eventually recovered. Clinicians should be mindful of the risk for systemic botulism when using local injections of the neurotoxin.