Case presentation
A 19 year-old adolescent woman with Dravet syndrome, characterized by epilepsy, global developmental delay, microcephaly, broad-based ataxic gait and hypothyroidism, presented with pallor and bruising. Her complete blood counts progressively decreased over a month (Table 1). Her hemoglobin was 5.9 g/dl, white blood cells 4,300/uL, and platelets 117,000/ul. Bone marrow biopsy showed 98% lymphoblasts. There was no central nervous system involvement. Immunophenotype analysis cytometry demonstrated B cell lineage with expression of CD10, CD19, CD22, CD34, CD38, CD45 (very dim) and HLA-DR. Cytogenetics revealed hyperdiploidy: 58, XX, +X, +4,+4, +5, I(7)(q10), +8, inv(9)(p12q13)c, +10,+13, +19, +20, +21, +21, +mar1[cp0]/59, idem, +mar2[2]/46, XX, inv(9)(p12q13)c[12]. FLT3 mutation not detected. Following her diagnosis of B-cell ALL, she received anti-leukemic therapy per Children’s Oncology Group AALL1732 and is currently in complete remission.
She had first demonstrated seizures at age of 4 months 2-3 days after her immunizations, which consisted of staring and lasted for as long as 1 minute. Phenobarbital was administered, but seizures continued. At age of 6 months, she started having left arm and leg jerking which worsened during fever or infection, then at age of 11 months, she developed grand mal seizures. At that time, general physical examination and neurological examination were unremarkable. Several blood tests, urine tests, brain computerized tomography scan, spinal fluid examination, and electroencephalogram showed normal results. She showed mild motor developmental and global delay involving speech delay. Magnetic resonance imaging confirmed right fronto-parietal malformation of cortical development. She tested negative for DNA methylation for Angelman syndrome/Prader-Willi syndrome. Her seizures were not significantly controlled despite the use of multiple anti-epileptic medications including phenobarbital, valproate, and lamotrigine. At age of 11 years, a pathogenic variant was identified SCN1A p. Ile227Ser. After then her treatment regimens were modified, and locasmide was replaced by clobazam which showed good response. During 2020, she was admitted because of decreased oral intake, emesis, and an inability to take medications for 4 weeks prior to admission accompanied by altered mental status and hallucinations a week prior to admission. She became dependent on G-tube feeding. After discharge, she was re-admitted shortly with weakness and instability. Since then, she has been receiving her anti-epilepsy drug cocktail. Her leukemia remains in continuous complete remission.
To determine the expression of SCN1A  in human hematopoietic cell lines, we used Bloodspot to generate a hierarchical differentiation tree based on SCN1A  expression. Bloodspot analyzed publicly available microarray data (GSE24759).3 The analysis revealed that B-cells progenitors have maximum expression of SCN1A  among different hematopoietic cells (Figure 1A ). Expression ofSCN1A in non-neural, lymphoid tissue was confirmed by analysis of datasets from Children’s Oncology Group P9906 (Figure 1B ), and normal and corresponding leukemia samples (Figure 1C ).4,5 SCN1A expression was markedly elevated in the REH cell line, which was derived from an adolescent girl with B cell ALL that harbors the ETV6::RUNX1 oncogene. Our patient had complex cytogenetics without that t(12;21) translocation.