Details

Autor(en) / Beteiligte

• Kelberman, Daniel, PhD
• Islam, Lily, MB BS, MRCPCH
• Jacques, Thomas S., PhD, MRCP
• Russell-Eggitt, Isabelle, FRCS, FRCOphth
• Bitner-Glindzicz, Maria, FRCP, PhD
• Khaw, Peng T., PhD, FRCS
• Nischal, Ken K., MB BS, FRCOphth
• Sowden, Jane C., PhD

Titel

CYP1B1 -Related Anterior Segment Developmental Anomalies

Ist Teil von

• Ophthalmology (Rochester, Minn.), 2011, Vol.118 (9), p.1865-1873

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2011

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Purpose To determine the prevalence of CYP1B1 mutations in a cohort of patients with congenital corneal opacification (CCO), infantile glaucoma, or both and to describe a developmental CCO associated with CYP1B1 mutation that may explain von Hippel's original description of an internal ulcer. Design Retrospective genotyping of a cohort of patients with infantile glaucoma and CCO. Participants Thirty-three patients with CCO, infantile glaucoma, or both. Methods All patients underwent a full clinical evaluation with or without examination under anesthetic including anterior segment photography, ultrasound biomicroscopy (for CCO patients; n = 22), and histopathologic analysis in patients in whom penetrating keratoplasty (PK) was performed (n = 10). Patient DNA and DNA from 50 normal control individuals who had undergone a full ophthalmologic examination were screened for CYP1B1 mutations. Main Outcome Measures Classification of the developmental corneal opacity phenotype in infantile glaucoma patients with CYP1B1 mutations. Results Nine distinct pathogenic recessive CYP1B1 mutations were found in 11 patients from 6 unrelated families, including 1 patient with an entire deletion of the CYP1B1 gene. Two of these patients, including the patient with the deletion, had isolated infantile congenital glaucoma with no other abnormalities. No CYP1B1 mutations were found in another 13 patients (7 of whom underwent PK in at least 1 eye) who had CCO with iridocorneal or keratolenticular adhesions (Peters' anomaly types I and II, respectively). Eight further children with CYP1B1 mutations who had CCO from birth and glaucoma underwent successful glaucoma treatment but had persistent diffuse CCO without iridocorneal or keratolenticular adhesions. Three of these underwent bilateral PK, and the histologic results were not consistent with any hitherto recognized congenital corneal dystrophy and showed abnormalities of the central corneal endothelium. Conclusions Both severe CCO and isolated infantile glaucoma are associated with CYP1B1 mutations. The severe CCO phenotype reported herein often requires PK and has typical histopathologic changes. The mutations associated with this phenotype have not been reported previously. This phenotype may explain the patient described by Von Hippel in 1897. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.