Expanding the mutational and phenotypical spectrum of FHONDA syndrome.

ABSTRACT

Foveal hypoplasia, optic nerve decussation, and anterior segment dysgenesis (FHONDA) is a rare recessively inherited syndrome first described in 2013. FHONDA is associated with biallelic disease-causing variants in the SLC38A8 gene, which has a strong expression in the photoreceptor layer. To date, 60 different disease-causing variants in the SLC38A8 gene have been described. In this cross-sectional case series, we included three unrelated female patients with FHONDA syndrome who presented with congenital nystagmus and decreased visual acuity from infancy. Best-corrected visual acuity was 20/100 OD and 20/60 OS for Patient 1 (P1) (72 years old); light perception OD and hand motion OS for Patient 2 (P2) (66 years old); and 20/100 OD and 20/100 OS for Patient 3 (P3) (25 years old). While normal retinal pigmentation was seen on P1 and P3, P2 presented retinal features of retinitis pigmentosa, including a pale optic nerve head, vessel thinning, and 360° dense bone spicule hyperpigmentation OU. Spectral-domain optical coherence tomography revealed grade 4 foveal hypoplasia in all patients. In P1 and P2, the novel class IV c.388 + 1G > T p.? variant in SLC38A8 was present in homozygosity; while P3 harboured the novel c.214G > C p.(Gly72Arg) variant in homozygosity, classified as class III. Thus, we expand the mutational spectrum of FHONDA by reporting two novel variants. In addition, we describe features of retinitis pigmentosa for the first time in a patient with biallelic homozygous SLC38A8 variants, thus broadening our understanding of the clinical phenotype associated with this rare syndrome.