François fleck dystrophy, or "fleck corneal dystrophy"

History

First described by François and Neetens

Genetics

AD

Mutation

Chromosome 2q35, mutation of the phosphoinositide kinase, FYVE finger-containing gene (PIKFYVE), formerly known as type III phosphatidylinositol-3-phosphate/phosphatidylinositol-5-kinase (PIP5K3).

Laterality

Bilateral

Symmetry

No

Age of onset

The abnormality is present from birth but is rarely diagnosed, since the majority of patients are asymptomatic.

Location

The keratocytes; this abnormality is present only in some keratocytes and not in all keratocytes.

Appearance:

Direct illumination

discrete translucent to gray-white punctate stromal opacities, distributed regularly and homogeneously from limbus to limbus, sparing Bowman layer as it is acellular. The specks may take on various appearances: circular, oval, star-shaped, or comma-shaped.

Retroillumination

The deposits have a refractile appearance.

Pain or recurrent erosion

No

Visual acuity

Usually preserved; patients are often asymptomatic.

Diagnosis:

• Histology: it is a combination of deposits similar to those of macular dystrophy and Schnyder dystrophy. The affected keratocytes are vacuolated by two substances: GAG (within membranous vacuoles), Alcian +, and lipids (in vacuoles smaller than the GAG vacuoles), Sudan black +.
• Electron microscopy: pleomorphic or linear extracellular vacuoles, sometimes with dense fibrillogranular membranous material, within certain keratocytes, resembling the inclusions found in macular dystrophies and in the mucopolysaccharidoses.
• Confocal microscopy: discrete gray-white stromal opacities corresponding to deposits of pathological material within keratocytes with enlarged nuclei, with inclusions in the basal corneal nerves.
• Corneal hypoesthesia may develop.