For a study, researchers sought to describe the foveal hypoplasia genotypic and phenotypic spectrum (FH). A total of 907 individuals with albinism, PAX6, SLC38A8, FRMD7, AHR, or achromatopsia with a confirmed molecular diagnosis from 12 facilities in 9 countries (n = 523) or derived from publically accessible datasets from previously reported literature (n = 384) were studied. Between January 2011 and March 2021, individuals with a verified molecular diagnosis and foveal OCT images were found from 12 centers or the literature. Sequence analysis validated a genetic diagnosis. OCT images were used to grade FH patients.
Albinism (67.5%) was the most prevalent genetic cause of typical FH in the sample, followed by PAX6 (21.8%), SLC38A8 (6.8%), and FRMD7 (3.5%) variations. AHR variations were uncommon (0.4%). In 67.4% of achromatopsia patients, atypical FH was found. In achromatopsia, atypical FH exhibited considerably lower VA than normal FH (P< 0.0001). Based on the molecular diagnosis, there was a substantial difference in the spectrum of FH grades (chi-square = 60.4, P<0.0001). PRS– (P=0.003) in all SLC38A8 instances, but PRS+ (P<0.0001) in all FRMD7 cases. Oculocutaneous albinism (OCA) was shown to have a significant difference in the grade of FH (chi-square = 31.4, P=0.0001) and VA (P=0.0003) when compared to ocular albinism (OA) and Hermansky–Pudlak syndrome (HPS). Ocular albinism and HPS had higher FH grades and lower VA than OCA. When FRMD7 variations were compared to other diagnoses linked with FH, there was a significant difference in VA (P<0.0001).
FH’s phenotypic and genotypic range was studied. Atypical FH has a poorer prognosis than all other types of FH. The findings implied that in typical FH, retinal development was interrupted sooner in SLC38A8, OA, HPS, and AHR variations and later in FRMD7 variants. For OCA and PAX6 mutations, the stated time period of foveal developmental stoppage appeared to be more variable. The findings gave mechanistic insight into FH-related illnesses and had great prognostic and diagnostic utility.