title: Microphthalmia, anophthalmia, and coloboma and associated ocular and systemic features: understanding the spectrum.
abstract: OBJECTIVE
  Microphthalmia, anophthalmia, and coloboma form an interrelated spectrum of congenital eye abnormalities.
  
  
  OBJECTIVE
  To document the ocular and systemic findings and inheritance patterns in patients with microphthalmia, anophthalmia, and coloboma disease to gain insight into the underlying developmental etiologies.
  
  
  METHODS
  This retrospective consecutive case series was conducted at a tertiary referral center. Included in the study were 141 patients with microphthalmia, anophthalmia, and coloboma disease without a recognized syndromic etiology who attended the Westmead Children's Hospital, Sydney, from 1981-2012.
  
  
  METHODS
  Cases were grouped on the basis of the presence or absence of an optic fissure closure defect (OFCD); those with OFCD were further subdivided into microphthalmic and nonmicrophthalmic cases. Anophthalmic cases were considered as a separate group.
  
  
  METHODS
  Associated ocular and systemic abnormalities and inheritance patterns were assessed.
  
  
  RESULTS
  Of 141 cases, 61 (43%) were microphthalmic non-OFCD (NOFCD), 34 (24%) microphthalmic OFCD, 32 (23%) nonmicrophthalmic coloboma (OFCD), 9 (6%) anophthalmic, and 5 (4%) were unclassified. Sixty-three (45%) had bilateral disease. Eighty-four patients (60%) had an associated ocular abnormality; of these, cataract (P < .001) and posterior segment anomalies (P < .001) were most common in the NOFCD group. Forty-eight (34%) had an associated systemic abnormality, most commonly neurological, musculoskeletal and facial, urological and genital, or cardiac. Neurological abnormalities were most common in the anophthalmic group (P = .003), while urological abnormalities were particularly seen in the OFCD groups (P = .009). Familial cases were identified in both the OFCD and NOFCD groups, with a likely autosomal dominant inheritance pattern in 9 of 10 families.
  
  
  CONCLUSIONS
  This series indicated that the OFCD/NOFCD distinction may be useful in guiding evaluation for ocular and systemic associations, as well as the direction and analysis of genetic investigation.
authors.affiliation: Discipline of Ophthalmology, University of Sydney, New South Wales, Australia3Department of Ophthalmology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Simon E
authors.initials: SE
authors.lastname: Skalicky
authors.affiliation: Discipline of Ophthalmology, University of Sydney, New South Wales, Australia2Eye and Developmental Genetics Research Group, Western Sydney Genetics Program, The Children's Hospital at Westmead, Sydney, New South Wales, Australia3Department of Ophthalmology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Andrew J R
authors.initials: AJ
authors.lastname: White
authors.affiliation: Discipline of Ophthalmology, University of Sydney, New South Wales, Australia2Eye and Developmental Genetics Research Group, Western Sydney Genetics Program, The Children's Hospital at Westmead, Sydney, New South Wales, Australia3Department of Ophthalmology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: John R
authors.initials: JR
authors.lastname: Grigg
authors.affiliation: Discipline of Ophthalmology, University of Sydney, New South Wales, Australia3Department of Ophthalmology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Frank
authors.initials: F
authors.lastname: Martin
authors.affiliation: Department of Ophthalmology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Smith
authors.affiliation: Discipline of Ophthalmology, University of Sydney, New South Wales, Australia3Department of Ophthalmology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Jones
authors.affiliation: Department of Ophthalmology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Craig
authors.initials: C
authors.lastname: Donaldson
authors.affiliation: Department of Ophthalmology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: James E H
authors.initials: JE
authors.lastname: Smith
authors.affiliation: Eye and Developmental Genetics Research Group, Western Sydney Genetics Program, The Children's Hospital at Westmead, Sydney, New South Wales, Australia3Department of Ophthalmology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Maree
authors.initials: M
authors.lastname: Flaherty
authors.affiliation: Discipline of Ophthalmology, University of Sydney, New South Wales, Australia2Eye and Developmental Genetics Research Group, Western Sydney Genetics Program, The Children's Hospital at Westmead, Sydney, New South Wales, Australia4Children's Medical Research Institute, Westmead, Sydney, New South Wales, Australia5Discipline of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Robyn V
authors.initials: RV
authors.lastname: Jamieson
mesh_terms: D000853:Anophthalmos / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D000869:Anterior Eye Segment / Q000002:abnormalities; D002386:Cataract / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003103:Coloboma / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D040582:Inheritance Patterns; D008297:Male; D008850:Microphthalmos / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D015835:Ocular Motility Disorders / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D012189:Retrospective Studies