FOXC1 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: Forkhead box C1
  • Transcription factor regulating the activity of other genes
  • Interacts with the PITX2 protein in influencing migration and differentiation of neural crest cells into distinct anterior segment structures
  • Also involved in the normal development of other parts of the body, including the heart, kidneys, and brain
Clinical phenotype
(OMIM phenotype no.)
  • Anterior segment dysgenesis 3, multiple subtypes (#601631)
  • Axenfeld-Rieger syndrome, type 3 (#602482)
Ocular features
  • High clinical variability between and within families
  • Some patients present with striking ocular features in infancy or early childhood while others are more subtle
  • Glaucoma is the main associated ocular co-morbidity
  • Axenfeld-Reiger anomaly (posterior embryotoxon, iris hypoplasia, polycoria, corectopia)
  • Primary congenital glaucoma
  • Peters anomaly
  • Strabismus (due to sensory deprivation amblyopia)
  • Reduced vision
  • Incidentally identified ocular hypertension and glaucomatous cupping in later life
Systemic featuresAxenfeld-Rieger syndrome:
  • Distinctive facial features (hypertelorism, broad, flat nasal bridge and a prominent forehead)
  • Dental abnormalities (micro-, hypo-, oligo-, and/or anodontia, taurodontism, enamel hypoplasia, shortened roots, delayed eruption and cone-shaped teeth)
  • Redundant periumbilical skin
  • Cardiovascular defects (patent ductus arteriosus, atrial/ventricular septal defect)
  • Brain maldevelopment (hydrocephalus, hypoplasia of the cerebellum, brainstem, and corpus callosum)
  • Sensorineural hearing loss
  • Genitourinary anomalies (hypospadias, ureteral stenosis)
  • Skeletal anomalies (clinodactyly)
  • Developmental delay
Key investigations
  • Orthoptic assessment and refraction
  • Ultrasound biomicroscopy and B-scan ultrasound: to assess the anterior and posterior segments in the presence of corneal clouding, corneal diameter and axial length measurements
  • Anterior segment OCT also allows visualisation of anterior segment structures if corneal oedema is present
  • Glaucoma assessment (IOP measurement, gonioscopy if tolerated or EUA, disc imaging and perimetry)
  • Electrophysiology: assess a child’s level of vision
  • Systemic screening by a paediatrician for any extraocular involvement
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (ASD)
  • Whole exome sequencing
  • Whole genome sequencing
  • Multidisciplinary approach
Therapies under research
  • None at present
Further information

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Updated on November 30, 2020
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