An inherited disorder with splenomegaly, cytopenias, and vision loss

Abstract

We describe a novel inherited disorder consisting of idiopathic massive splenomegaly, cytopenias, anhidrosis, chronic optic nerve edema, and vision loss. This disorder involves three affected patients in a single non-consanguineous Caucasian family, a mother and two daughters, who are half-sisters. All three patients have had splenectomies; histopathology revealed congestion of the red pulp, but otherwise no abnormalities. Electron microscopic studies of splenic tissue showed no evidence for a storage disorder or other ultrastructural abnormality. Two of the three patients had bone marrow examinations that were non-diagnostic. All three patients developed progressive vision loss such that the two oldest patients are now blind, possibly due to a cone-rod dystrophy. Characteristics of vision loss in this family include early chronic optic nerve edema, and progressive vision loss, particularly central and color vision. Despite numerous medical and ophthalmic evaluations, no diagnosis has been discovered.

FIG. 1

Family tree: Case 1 is Patient III-2 in the pedigree; Case 2 (the mother) is Patient II-3 in the pedigree; and Case 3 (half-sister) is Patient III-1 in the pedigree.

FIG. 2

Representative fundus photos and optic disc photo from this cohort. Shown are fundus photos of Patient III-2. A: Fundus montage photo of the right eye. B: Fundus montage photo of left eye of Patient III-2 at age 20. At the time of the photos, best corrected vision was 20/50 OD, and 20/150 OS. These photographs are representative of the other affected family members. Note: Optic disc edema, flame hemorrhages, and attenuated blood vessels.

FIG. 3

Fundus montage photo from the left eye of patient III-1 at age 24. Her vision at this time was light perception only. Opacities and inflammation in the anterior chamber, lens capsule, and vitreous limit the view of the fundus. There is marked attenuation of retinal vessels, particularly arterioles, and optic nerve pallor.

FIG. 4

ERG findings from Patient III-1 showing mildly diminished oscillatory potentials at age 7 progressing to marked attenuation by age 15.

FIG. 5

Multifocal ERG from Patient III-2 at age 13 (top) showing severe cone depression in the macula. Normal field is shown below for comparison.

FIG. 6

Fluorescein angiogram from Patient III-2 at age 14. The angiogram shows leakage from the optic nerve, but no vasculitis or cystoid macular edema. The times indicated are in minutes and seconds from injection of fluorescein. Images A, B, D, and F are from the right eye; images C and E are from the left eye.