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.