Keratoconus in hereditary spastic paraplegia 15 and Kjellin syndrome: a case report.

Background: Hereditary spastic paraplegia 15 (HSP15) is a rare genetic disease manifesting with progressive muscle spasticity and paralysis of the lower limbs (paraplegia) caused by mutations in the ZFYVE26 gene. When spastic paraplegia is accompanied by retinal degeneration and cognitive impairment, it is known as Kjellin syndrome. We report on ocular manifestations in a case with HSP15 and Kjellin syndrome.

Materials and methods: We follow a 26-year-old male patient with HSP15 for 6 years. His condition was confirmed by clinical exome sequencing. In addition to regular systemic follow-ups, we performed ophthalmic examinations that included best corrected visual acuity, color vision testing, stereo acuity, visual fields, fundus photography, fundus autofluorescence, optical coherence tomography (OCT), OCT angiography, and corneal topography.

Results: Genetic testing in the patient revealed homozygosity for the pathogenic variant c.2114dupC; p. (Glu706Ter) in the ZFYVE26. Although the variant is present in population databases and ClinVar, this is the first report of this variant in HSP15 affected patient. During follow-up the patient's visual acuity declined. Ocular fundus findings comprised of slowly progressive retinal degeneration and a novel ocular phenotype in HSP15 - keratoconus. Corneal topography showed corneal thinning (thinnest location OD: 524 µm OS: 490 µm). Keratoconus was classified as RE: A1B2C0D1, LE: A3B4C1D3 according to Belin Keratoconus Staging System.

Conclusion: We describe the clinical and ocular manifestations of a patient with HSP15 and Kjellin syndrome who was diagnosed with a pathogenic variant of ZFYVE26 gene. The patient developed keratoconus that to our knowledge is a novel ophthalmic phenotype in HSP15.