876:
Hyper-Eosinophilic Syndrome and Partial Duplication of Chromosome 21
Monday, March 5, 2018
South Hall A2 (Convention Center)
Dikla Adir, MD, Shira Benor, Dror Levin, David Hagin, MD
RATIONALE: Hyper-Eosinophilic Syndrome (HES) represents a heterogeneous group of conditions and can be either idiopathic or secondary to variety of underlying causes. We present a novel etiology for severe hypereosinophilia in a pediatric patient.

METHODS: An 8y/o boy presented with fever, gastrointestinal symptoms, worsening of background asthma and an absolute eosinophil count of ~40,000. Screening for end-organ damage was negative and he was treated empirically for a possible helminth infection. The patient responded well to corticosteroids but eosinophil counts rose upon prednisone taper. Bone-marrow (BM) biopsy was normal except for significantly increased eosinophils. TCR repertoire and screening for associated genetic abnormalities (BCR-ABL1, FIP1L1-PDGFRA, PDGFRB rearrangement) was negative. Despite normal karyotype, cytogenetic studies were performed in search for chromosomal aberrations.

RESULTS: FISH studies using probes to detect AML/ALL associated translocations, revealed a triple signal of the chromosome 21 probe in 20% of BM cells. The probe staining pattern, with close proximity of 2 of the 3 hybridization signals, suggested a partial duplication of chromosome 21. The percent of triple-21-probe cells did not correlate with 50% eosinophils in BM and FISH of skin fibroblasts or peripheral blood. Taken together, these findings support a somatic variation, possibly in a non-eosinophilic cell lineage. Interestingly, the probe used was complementary to RUNX1 (AML1), a transcription factor involved in differentiation of hematopoietic stem cells into myeloid and lymphoid lines.

CONCLUSIONS:

RUNX1 copy number variance might drive eosinophil proliferation and cytogenetic studies should be considered in the evaluation of HES.