Pediatric recurrent acute necrotizing encephalomyelitis, RANBP2 genotype and Sars-CoV-2 infection: Diagnosis, pathogenesis and targeted treatments from a case study.

Acute necrotizing encephalopathy (ANE) is a rare disease not yet described in children with Covid-19. RANBP2 gene variations are implicated in recurrences in the genetic form of ANE, the so called ANE1. We report the first case of pediatric ANE1 following Sars-CoV-2 infection. She had a first episode at 2 years of age following influenza type A with full recovery, many other respiratory and non-respiratory febrile viral infections without recurrences and a severe recurrence following Sars-CoV-2 infection, suggesting a potentiation effect on cytokine cascade. Her MRI showed the typical pattern of injury resembling that of mitochondrial disorders, and supported the role of RANBP2 in mitochondrial homeostasis. This case rises attention on diagnostic challenges and offers several interesting tips for discussion about new perspectives in pathogenesis and targeted treatments.

ELP2 compound heterozygous variants associated with cortico-cerebellar atrophy, nodular heterotopia and epilepsy: Phenotype expansion and review of the literature.

The elongator complex is a highly conserved macromolecular assembly composed by 6 individual proteins (Elp 1-6) and it is essential for many cellular functions such as transcription elongation, histone acetylation and tRNA modification. ELP2 is the second major subunit and with Elp1 and Elp3 it shapes the catalytic core of this essential complex. ELP2 gene pathogenic variants have been reported to be associated with several neurodevelopmental disorders, such as intellectual disability, severe motor development delay with truncal hypotonia, spastic diplegia, choreoathetosis, short stature and neuropsychiatric problems. Here we report a case with heterozygous variants of the ELP2 gene associated with unpublished electro-clinical and neuroimaging features, such as abnormal eye movements, focal epilepsy, cortico-cerebellar atrophy and nodular cortical heterotopia on brain MRI. A possible phenotype-genotype correlation and the electro-clinical and neuroimaging phenotype expansion of ELP2 mutations are here discussed, together with considerations on involved cortico-cerebellar networks and a detailed review of the literature.

Jak2 mutation expands the thrombophilic panel in children.

Cerebral sinus venous thrombosis (CSVT) is an important cause of vascular accidents in children. The diagnosis of the underlying disease allows appropriate and timely management of the risk factors and guide therapy, but the etiology remains unknown in 20% to 25% of the cases. We present the first case of a child presenting with CSVT caused by the Janus Kinase 2 (JAK2) V617F mutation, occurring without the hematological abnormalities diagnostic for myeloproliferative neoplasms. We therefore suggest including the molecular study of the JAK2 gene in the coagulation panel of all children affected by CSVT of unknown cause.