title: A broad range of ophthalmologic anomalies is part of the holoprosencephaly spectrum.
abstract: Holoprosencephaly (HPE) is the most common disorder of the developing forebrain in humans, and is characterized by failed or incomplete cleavage of the cerebral hemispheres and deep brain structures. HPE includes wide phenotypic variability, with a continuum of both brain and craniofacial anomalies. While "classic" eye findings, including the spectrum of midline anomalies ranging from cyclopia to hypotelorism, as well as chorioretinal coloboma and microphthalmia, have been frequently described in patients with HPE, other subtle eye anomalies may also occur. In our study we prospectively analyzed a small cohort of 10 patients in whom we identified mutations in SHH, SIX3, ZIC2, or FGF8, the latter of which is a very recently described HPE-associated gene. We found that 9 of 10 patients had at least two ophthalmologic anomalies, including refractive errors, microcornea, microphthalmia, blepharoptosis, exotropia, and uveal coloboma. These findings contribute to the understanding of the phenotypic variability of the HPE spectrum, and highlight findings in one medically important but often incompletely investigated system.
authors: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20814, USA.
authors: Daniel E
authors: DE
authors: Pineda-Alvarez
authors: Benjamin D
authors: BD
authors: Solomon
authors: Erich
authors: E
authors: Roessler
authors: Joan Z
authors: JZ
authors: Balog
authors: Donald W
authors: DW
authors: Hadley
authors: Wadih M
authors: WM
authors: Zein
authors: Casey K
authors: CK
authors: Hadsall
authors: Brian P
authors: BP
authors: Brooks
authors: Maximilian
authors: M
authors: Muenke
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D019465:Craniofacial Abnormalities / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D005128:Eye Diseases / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D053823:Hedgehog Proteins / Q000235:genetics; D016142:Holoprosencephaly / Q000235:genetics / Q000473:pathology*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D010641:Phenotype; D010808:Physical Examination; D011446:Prospective Studies; D000097607:Homeobox Protein SIX3
chemical_list: D005136:Eye Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000097607:Homeobox Protein SIX3; C509239:SHH protein, human