Lacrimal Gland Involvement in Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome

Abstract

To describe the involvement of the lacrimal gland (LG) in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). Observational, cross-sectional study. Twenty-one patients with BPES (10 female, 11 male) aged on average 15 years (range, 2-39years), from 3 Brazilian medical centers and 1 Portuguese medical center. Patients had their ocular surface evaluated with slit-lamp biomicroscopy, and tear production quantified with the Schirmer test I. The LG volumes were measured on computed tomography (CT) scans in the BPES sample and in a group of age-matched subjects imaged for nonorbital diseases. Sixteen patients were screened for mutations in the FOXL2 gene. Lacrimal meniscus height, Schirmer test I, presence of superficial punctate keratopathy (SPK), LG volume, and molecular analysis of the FOXL2 gene. Absence of LG was detected bilaterally in 9 patients (42.8%) and unilaterally in 2 patients (9.5%). When considering only patients with measurable LG, the median volume was 0.22 cm3 in the right eye (range, 0.06-0.36 cm3) and 0.24 cm3 in the left eye (range, 0.08-0.34 cm3). These values were significantly lower than those for the age-matched controls (median= 0.54 right eye and 0.53 left eye; P < 0.05). There was a significant association between deficiency of tear production and LG volume reduction and agenesis. Molecular analysis of the FOXL2 gene revealed the presence of 8 distinct mutations, 4 of them novel ones. A significant reduction of LG size or agenesis was associated with mutations affecting protein size (due to underlying changes in the stop codon location) or the DNA-binding forkhead domain (Fisher exact test, P= 0.021). In 3 probands, the underlying genetic defect was not found. This is the first study reporting LG volumes in BPES, describing a significant number of patients with LG agenesis. The association between alacrima and BPES is not incidental, and a thorough evaluation of tear production is recommended especially if ptosis surgery is planned.