title: 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, 2-39 years), 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 cm3in the right eye (range, 0.06-0.36 cm3) and 0.24 cm3in 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.
authors.affiliation: Division of Oculoplastic and Orbit Surgery, Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Ana Filipa
authors.initials: AF
authors.lastname: Duarte
authors.affiliation: Division of Oculoplastic and Orbit Surgery, Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Patricia M S
authors.initials: PM
authors.lastname: Akaishi
authors.affiliation: Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Greice A
authors.initials: GA
authors.lastname: de Molfetta
authors.affiliation: Department of Radiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Salomão
authors.initials: S
authors.lastname: Chodraui-Filho
authors.affiliation: Department of Radiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Murilo
authors.initials: M
authors.lastname: Cintra
authors.affiliation: Division of Pediatric Ophthalmology and Strabismus, Centro Hospitalar de Lisboa Central, Lisbon, Portugal.
authors.forename: Alcina
authors.initials: A
authors.lastname: Toscano
authors.affiliation: Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Wilson Araujo
authors.initials: WA
authors.lastname: Silva
authors.affiliation: Division of Oculoplastic and Orbit Surgery, Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: aavecruz.fmrp@gmail.com.
authors.forename: Antonio A V
authors.initials: AA
authors.lastname: Cruz
mesh_terms: D000293:Adolescent; D000328:Adult; D016569:Blepharophimosis / Q000000981:diagnostic imaging* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005124:Eye Abnormalities / Q000000981:diagnostic imaging* / Q000235:genetics; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005784:Gene Amplification; D056726:Genetic Association Studies; D006801:Humans; D007765:Lacrimal Apparatus / Q000002:abnormalities*; D008297:Male; D012868:Skin Abnormalities / Q000000981:diagnostic imaging* / Q000235:genetics; D000072776:Slit Lamp Microscopy; D013666:Tears / Q000502:physiology; D014057:Tomography, X-Ray Computed; D014564:Urogenital Abnormalities / Q000000981:diagnostic imaging* / Q000235:genetics
chemical_list: C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors