Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) due to polyAla site variant in FOXL2: diagnostic challenges with NGS

This report presents a case of blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) identified in a term neonate. This patient presented with the four typical ophthalmic signs: short horizontal palpebral fissures (blepharophimosis), impaired levator palpebrae superioris muscle function leading to drooping of upper eyelids (ptosis), skin folding on the medial lower eyelid ascending to the upper eyelid (epicanthus inversus) and increased medial intercanthal distance (telecanthus). On genetic analysis, a polyalanine (polyAla) tract expansion in the FOXL2 gene was identified. Through this report, we highlight the importance of understanding the limitations of different genetic tests when investigating diseases with polyalanine tract expansion mutations such as BPES.