Autosomal dominant foveal hypoplasia without visible macular abnormalities and PAX6 mutations.

PURPOSE: Autosomal dominant foveal hypoplasia (FVH1) is a rare disorder associated with mutations in the PAX6 gene. As an isolated disease entity, FVH1 does not include ocular disorders such as aniridia, microphthalmia, albinism, and achromatopsia. However, it only includes isolated foveal hypoplasia and foveal hypoplasia with presenile cataract. The purpose of this report is to present our findings in four patients from two families with FVH1 without visible ophthalmic macular abnormalities.

STUDY DESIGN: A review of the medical records of two families with FVH1 and genetic confirmation of mutations in the PAX6 gene.

METHODS: Fundus photographs, optical coherence tomographic (OCT) and OCT angiographic (OCTA) images, and slit-lamp anterior segment findings were determined. The type of mutation of the PAX6 gene was determined.

RESULTS: A 3-year-old girl (Patient 1) had signs and symptoms of an impairment in the development of vision without other retinal abnormalities OU. OCT images showed a shallow foveal pit, and OCTA showed the absence of the foveal avascular zone. The second patient (Patient 2) was a 6-year-old girl with unilateral mild cataract and shallow foveal pits OU. Similar shallow foveal pits were found in her asymptomatic mother (Patient 3) and maternal grandfather (Patient 4). Although the iris and posterior fundus were normal, all patients with FVH1 had goniodysgenesis. Genetic testing of the PAX6 gene revealed that Patient 1 had a novel heterozygous mutation (p.Asn365Lys) as a de novo mutation, and Patients 2, 3 and 4 had a novel heterozygous mutation (p.Pro20Ser).

CONCLUSIONS: Heterozygous mutations in the PAX6 gene can cause FVH1 with nearly normal appearing macula. FVH1 is difficult to diagnose, but detailed observations of the foveal structure and vasculature, and detecting the presence of goniodysgenesis can be helpful in identifying patients with FVH1.