Nonetheless, no gene polymorphisms were found within the promoters, exons, or introns of these 3 genes or in the regions IL-3/GM-CSF enhancer. In addition to these studies, 8 affected members of a family with familial eosinophilia had peripheral blood or bone marrow cells that carried the same chromosome abnormality, a pericentric inversion of chromosome 10, inv (10) (p11.2q21.2). The meaning and relationship, if any, of this inversion to familial eosinophilia is unclear. Pathophysiology
Earlier studies found no evidence of abnormal blood levels of interleukin 5, interleukin 3, or granulocyte-macrophage colony stimulating factor. A more recent study used a more sensitive assay for interleukin 5 to compare members of a single extended family with some members lacking the disorder. The study found that members with the disorder had: a) peripheral blood mononuclear cells as well as T helper cells (major physiological source of interleukin 5), CD8+ cells, CD14+ cells, and CD19+ cells that expressed high levels of messenger RNA for interleukin 5 while their peripheral blood mononuclear cells expressed normal levels of messenger RNA for RAD50, a gene in close proximity to IL-5; b) elevated serum levels of interleukin 5 as well as soluble Interleukin 5 receptor alpha subunit; and c) innate lymphoid cells (also major physiological sources of interleukin 5) that produced increased amounts of interleukin 5 in response to stimulation. A second family with asymptomatic eosinophilia over three generations likewise exhibited increased production of interleukin 5.
These studies suggest that the dis-regulated overproduction of interleukin 5 by blood mononuclear cells is an underlying cause of the eosinophilia found in at least some families with this disorder. Diagnosis
The diagnosis of familial eosinophilia rest upon a) familial clustering of the disorder; b) exclusion of "family acquired eosinophilia" (i.e. eosinophilia due to chronic parasite or other infestations that afflict multiple members of a family); c) lack of eosinophil-induced tissue destruction such as that which occurs in the hypereosinophilic syndrome; d) absence of signs or symptoms of other hereditary eosinophilias (e.g. hyperimmunoglobulin E syndrome, Omenn syndrome), Wiskott–Aldrich syndrome, and numerous other primary immunodeficiency syndromes); and d) lack of evidence for reactive eosinophilias (e.g. allergy-related), neoplastic eosinophilias (e.g. eosinophilic leukemia, clonal eosinophilia), or eosinophila associated with various hematological and non-hematological malignancies as outlined in causes of eosinophilia. Treatment
Since longitudinal data, including eosinophil counts obtained over a 20- to 30-year periods in some family members, show remarkable stability in the absolute eosinophil count with no evidence of disease   attributable to eosinophil-related tissue injury, therapy to lower eosinophil counts such as corticosteroids, tyrosine kinase inhibitors, and antibodies directed against interleukin 5 have in general not been used to treat familial eosinophilia. One patient with severe heart damage was treated with a corticosteroid but soon thereafter died. Familial eosinophilia unassociated with possible eosinophil-related tissue injuries may not require drug treatment, those cases with such tissue injuries, it is suggested, should be considered for such interventions. In all cases, however, regular follow-up of the disorder is strongly recommended.