title: Corneal alterations in Crisponi/CISS1 syndrome: A slit-lamp biomicroscopy and in vivo confocal microscopy corneal report.
abstract: Mutations in the cytokine receptor-like factor 1 (CRLF1) gene are responsible for Crisponi/Cold-induced Sweat Syndrome, an extremely rare autosomal-recessive multisystem disorder. The protein encoded is a soluble cytokine receptor, involved in the ciliary neurotrophic factor receptor (CNTFR) pathway. The ciliary neurotrophic factor (CNTF) promotes corneal wound healing and patients with Crisponi/CISS1 syndrome suffer from recurrent keratitis. The aim of the study was to report and discuss the corneal alterations in Crisponi/CISS1 rare disease.
  
  
  
  We evaluated the cornea of both eyes in four Crisponi/CISS1 patients to provide a detailed description of slit-lamp biomicroscopy findings. Corneal sensitivity, tears functionality and blinking video recording at rest were also assessed in all patients. Two patients were also evaluated with in vivo confocal microscopy, completed with a needle electromyography of their orbicularis muscles.
  
  
  
  None of the patients presented a tears dysfunction and video recording documented a prolonged lid excursion in all patients. Slit lamp examination revealed a chronic epithelial impairment in all cases. Needle electromyography of the orbicularis oculi showed a dystonic pattern. The confocal microscopy confirmed the biomicroscopic observed lesions and documented unusual findings of the corneal nerve plexus.
  
  
  
  This is the first report of microscopic cornea alterations explored with confocal imaging in Crisponi/CISS1 patients. The observed corneal findings suggest a possible direct correlation to the CNTFR pathway defect and the blinking imbalance could exacerbate the compromised epithelial wound healing. Topical administrations of lubricating eye drops are strongly recommended in these patients.
authors.affiliation: a Ophthalmology Division , Catholic University of "Sacro Cuore ," Rome , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Agresta
authors.affiliation: a Ophthalmology Division , Catholic University of "Sacro Cuore ," Rome , Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Fasciani
authors.affiliation: b Neurology Division , Catholic University of "Sacro Cuore" , Rome , Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Padua
authors.affiliation: c Ophthalmology Division , "Bambino Gesù" Pediatric Hospital , Rome , Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Petroni
authors.affiliation: d Pediatric Division , Catholic University of "Sacro Cuore" , Rome , Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: La Torraca
authors.affiliation: a Ophthalmology Division , Catholic University of "Sacro Cuore ," Rome , Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Dickmann
authors.affiliation: d Pediatric Division , Catholic University of "Sacro Cuore" , Rome , Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zampino
authors.affiliation: a Ophthalmology Division , Catholic University of "Sacro Cuore ," Rome , Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Caporossi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003315:Cornea / Q000294:innervation; D003316:Corneal Diseases / Q000175:diagnosis*; D003645:Death, Sudden; D004576:Electromyography; D019573:Epithelium, Corneal / Q000473:pathology*; D019066:Facies; D005260:Female; D006228:Hand Deformities, Congenital / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D006945:Hyperhidrosis / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D018613:Microscopy, Confocal; D009801:Oculomotor Muscles / Q000502:physiology; D066167:Slit Lamp; D020433:Trigeminal Nerve Diseases / Q000175:diagnosis; D014313:Trismus / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D055815:Young Adult
keywords: Confocal microscopy; Crisponi/CISS1 syndrome; cornea