Abstract

Study design: Cross sectional observational study
Purpose: We report an unusual association between ARM, Bitot’s spots and vitamin A deficiency in a large series of our patients
Methods: Consecutive unrelated ARM patients were evaluated. After finding a high prevalence of Bitot's spots in these patients, serum vitamin A levels were determined for the probands and their mothers. Genetic evaluation was also carried out.
Results: Out of 70 patients, 16 were found to have Bitot’s spots in addition. All these 16 patients, and their mothers, had reduced serum vitamin A levels. All the Bitot’s spots were refractory to vitamin A supplementation. 4 had familial transmission both ARM and Bitot’s. Clinical exome sequencing revealed the presence of FOXC1 and PITX2 mutations.
Conclusions: This clinical study points to the role of retinoic acid metabolism in regulation of FOXC1 and PITX2 genes and causation of ARM. Further molecular studies are warranted to establish a cause-and-effect relationship