Axenfeld-Rieger syndrome

Axenfeld-Rieger syndrome (ARS), also known as Axenfeld anomaly, Rieger anomaly, or Rieger syndrome, is a rare genetic disorder primarily affecting the eyes, but often involving other body systems as well. It encompasses a spectrum of developmental abnormalities of the anterior segment of the eye, including posterior embryotoxon (a prominent, anteriorly displaced Schwalbe line), iris hypoplasia, corectopia (displaced pupil), polycoria (multiple pupils), and iridocorneal adhesions (iris strands bridging to the cornea). Approximately 50% of affected individuals develop glaucoma, typically in childhood or early adulthood, which can lead to vision loss if untreated. Beyond the eyes, Axenfeld-Rieger syndrome frequently involves craniofacial, dental, and abdominal features. Common extraocular findings include midface hypoplasia (flattened midface), dental anomalies such as microdontia (small teeth), oligodontia (missing teeth), and redundant periumbilical skin or umbilical hernia. Some individuals may also have pituitary abnormalities leading to growth hormone deficiency and short stature. Cardiac defects and hearing loss have been reported in some cases. Axenfeld-Rieger syndrome is most commonly caused by pathogenic variants in the PITX2 gene (chromosome 4q25) or the FOXC1 gene (chromosome 6p25), both of which encode transcription factors critical for embryonic development of the anterior segment of the eye and other structures. Inheritance follows an autosomal dominant pattern with high penetrance but variable expressivity, meaning that affected family members may show different combinations and severity of features. Treatment is primarily directed at managing glaucoma through medications (such as topical beta-blockers or prostaglandin analogs), laser therapy, or surgical intervention (trabeculotomy, goniotomy, or glaucoma drainage devices). Dental anomalies may require orthodontic or prosthetic management, and growth hormone deficiency, when present, can be treated with hormone replacement therapy. Regular ophthalmologic monitoring beginning in infancy is essential for early detection and management of elevated intraocular pressure.

Common questions about Axenfeld-Rieger syndrome