title: [Glaucoma with aniridia and isolated congenital glaucoma in siblings: contribution and limits of genetics].
abstract: BACKGROUND
  Congenital glaucoma associated with aniridia and primary congenital glaucoma are regarded as different entities. Indeed, the abnormalities of the angle's structures as well as the genes involved are different. We report the observation of two sisters presenting these two types of glaucoma with particular attention paid to the importance and the difficulty of genetic counseling.
  
  
  METHODS
  Child L, with no particular family history, had presented bilateral aniridia complicated by bilateral glaucoma since birth. In addition to medical and surgical treatment, general and genetic investigations were undertaken that revealed no abnormalities. No microdeletion of the gene PAX6 responsible for the aniridia was found. Consequently, the genetic advice was in favor of a second pregnancy for this couple. At birth, L's sister also presented bilateral congenital glaucoma, which was isolated, without aniridia. New genetic investigations were carried out but no abnormalities in PAX6, nor in FOXC1 or PITX2 involved in the development of the anterior chamber, were found. Moreover, the haplotypes for aniridia locus AN2 inherited by the two sisters were different, proof that this gene could not be responsible for the glaucoma.
  
  
  CONCLUSIONS
  At L's birth, the hypothesis retained was that she was a sporadic case whose gene mutation could not be identified (which happens in 50% of sporadic cases). The risk for the second pregnancy was negligible, although not null. The primary congenital glaucoma presented by L's sister remains unexplained in the context of aniridia and the role of the PAX6 gene was eliminated. The study of PITX2 and FOXC1 genes involved in anterior segment dysgenesis proved that they were also not involved. Thus, this observation evokes the responsibility of a gene other than PAX6 in aniridia, which could also have a role in isolated congenital glaucoma.
  
  
  CONCLUSIONS
  Analysis of congenital pathologies from a more genetic than clinical point of view seems to progressively break down the barriers established between the various phenotypes of hereditary congenital anomalies. Even if the association of aniridia and primary congenital glaucoma in siblings is reported here for the first time, it does not appear so extraordinary if one considers the complexity of the anterior chamber's development, which involves many genes, most of them still unidentified to date.
authors.affiliation: Service d'Ophtalmologie, CHU de Nice, Hôpital Saint Roch, Nice, France.
authors.forename: B
authors.initials: B
authors.lastname: Lise-Schneider
authors.forename: P
authors.initials: P
authors.lastname: Calvas
authors.forename: O
authors.initials: O
authors.lastname: Roche
authors.forename: J C
authors.initials: JC
authors.lastname: Lambert
authors.forename: J L
authors.initials: JL
authors.lastname: Dufier
authors.forename: C
authors.initials: C
authors.lastname: Costet-Fighiera
mesh_terms: D000328:Adult; D015783:Aniridia / Q000150:complications*; D000867:Anterior Chamber / Q000196:embryology; D000941:Antigens / Q000235:genetics; D015715:Corneal Edema / Q000151:congenital; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D005817:Genetic Counseling; D005901:Glaucoma / Q000151:congenital* / Q000196:embryology / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D006871:Hydrophthalmos / Q000209:etiology* / Q000235:genetics; D007231:Infant, Newborn; D007621:Karyotyping; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D011247:Pregnancy; D011509:Proteoglycans / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012306:Risk; D035781:Siblings; D014157:Transcription Factors / Q000235:genetics; D000097577:Homeobox Protein PITX2; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D005136:Eye Proteins; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011509:Proteoglycans; D012097:Repressor Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; D000099216:Chondroitin Sulfate Proteoglycan 4; C112743:FOXC1 protein, human; C000605730:PAX6 protein, human