Lacrimal Gland Involvement in Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome

• Autor(a) principal: Duarte, AF
• Data de Publicação: 2016
• Outros Autores: Akaishi, P, Molfetta, G, Chodraui-Filho, S, Cintra, M, Toscano, A, Araujo Silva, W, A v Cruz, A
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.17/2597
• topic: CHLC OFT; Blepharophimosis/diagnostic imaging; Blepharophimosis/genetics; Cross-Sectional Studies; DNA Mutational Analysis; Exons/genetics; Eye Abnormalities/diagnostic imaging; Eye Abnormalities/genetics; Forkhead Transcription Factors/genetics; Gene Amplification; Gene Association Studies; Lacrimal Apparatus/abnormalities; Skin Abnormalities/diagnostic imaging; Skin Abnormalities/genetics; Slit Lamp Microscopy; Tears/physiology; Tomography, X-Ray Computed; Urogenital Abnormalities/diagnostic imaging; Urogenital Abnormalities/genetics

PURPOSE: To describe the involvement of the lacrimal gland (LG) in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). DESIGN: Observational, cross-sectional study. PARTICIPANTS: Twenty-one patients with BPES (10 female, 11 male) aged on average 15 years (range, 2-39 years), from 3 Brazilian medical centers and 1 Portuguese medical center. METHODS: 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. MAIN OUTCOME MEASURES: Lacrimal meniscus height, Schirmer test I, presence of superficial punctate keratopathy (SPK), LG volume, and molecular analysis of the FOXL2 gene. RESULTS: 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. CONCLUSIONS: 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.