title: Ocular manifestations of 22q11.2 microduplication.
abstract: OBJECTIVE
  To report a new ocular manifestation of the dup22q11 syndrome and explore involved genes that may offer insight to mechanisms of pathogenesis.
  
  
  METHODS
  Case series.
  
  
  METHODS
  Two male patients with this syndrome diagnosed with dup22q11.2.
  
  
  METHODS
  Medical records were reviewed. Duplication was detected in the oligo-single nucleotide polymorphism chromosomal microarray and duplicated genes within the segment where determined by literature and database review. Potential associations between the ophthalmologic manifestations and their physiopathology were investigated.
  
  
  METHODS
  Microarray results and identification of candidate genes within the duplicated segment.
  
  
  RESULTS
  Our patients demonstrate previously unreported findings of dup22q11.2, including Marcus Gunn jaw winking, Duane's retraction syndrome, and other abnormal eye movements consistent with a congenital cranial dysinnervation disorder (CCDD), retinal vascular tortuosity, and primary infantile glaucoma. The duplicated segment in case 1 includes SNAP29, which could be linked with the development of retinal vascular tortuosity, and MAPK1, which seems to play a role in axonal development through the semaphorin pathway, which may serve as a candidate gene for CCDD. In case 2, the CLDN5 gene is within the duplicated segment. CLDN5 could be involved in the pathophysiology of glaucoma.
  
  
  CONCLUSIONS
  Our cases expand the ocular phenotype for duplication of 22q11 and serve to identify potential candidate genes for the development of CCDD, retinal vascular tortuosity, and glaucoma.
authors: Ocular Genetics, Wills Eye Institute, Philadelphia, Pennsylvania.
authors: Jose A
authors: JA
authors: Cordovez
authors: Ocular Genetics, Wills Eye Institute, Philadelphia, Pennsylvania.
authors: Jenina
authors: J
authors: Capasso
authors: Ocular Genetics, Wills Eye Institute, Philadelphia, Pennsylvania.
authors: Michelle D
authors: MD
authors: Lingao
authors: Ocular Genetics, Wills Eye Institute, Philadelphia, Pennsylvania.
authors: Karthikeyan A
authors: KA
authors: Sadagopan
authors: Glaucoma Service, Wills Eye Institute, Philadelphia, Pennsylvania.
authors: George L
authors: GL
authors: Spaeth
authors: Ocular Genetics, Wills Eye Institute, Philadelphia, Pennsylvania; Thomas Jefferson University, Philadelphia, Pennsylvania.
authors: Barry N
authors: BN
authors: Wasserman
authors: Ocular Genetics, Wills Eye Institute, Philadelphia, Pennsylvania; Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: alevin@willseye.org.
authors: Alex V
authors: AV
authors: Levin
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D001763:Blepharoptosis / Q000175:diagnosis* / Q000235:genetics; D002648:Child; D002869:Chromosome Aberrations; D058674:Chromosome Duplication / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D062507:Claudin-5 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D004062:DiGeorge Syndrome / Q000175:diagnosis* / Q000235:genetics; D004370:Duane Retraction Syndrome / Q000175:diagnosis* / Q000235:genetics; D005901:Glaucoma / Q000175:diagnosis* / Q000235:genetics; D006330:Heart Defects, Congenital / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007429:Intraocular Pressure; D007569:Jaw Abnormalities / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D046228:Microarray Analysis; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics; D009422:Nervous System Diseases / Q000175:diagnosis* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D050766:Qb-SNARE Proteins / Q000235:genetics; D050767:Qc-SNARE Proteins / Q000235:genetics; D012021:Reflex, Abnormal / Q000235:genetics; D012164:Retinal Diseases / Q000175:diagnosis* / Q000235:genetics; D012171:Retinal Vessels / Q000473:pathology*; D000093922:Congenital Cranial Dysinnervation Disorders
chemical_list: C107466:CLDN5 protein, human; D062507:Claudin-5; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; C432420:SNAP29 protein, human; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1