JOIN NOW

From Iris to Incisors: Axenfeld – Rieger Syndrome – Genetics with a Twist

by | Aug 1, 2024 | Manuscripts | 0 comments

Aishi Bhowmik B. Optom Student

Vidyasagar College of Optometry & Vision Science; Internship, L. V. Prasad Eye Institute, Bhubaneswar, India

 

Understanding a rare genetic disorder

Axenfeld –Rieger Syndrome ( ARS) (1) stands as a captivating enigma within the realm of genetic disorders, which unveils a profound impact on the development of crucial organs, particularly the eyes and teeth while occasionally extending its reach. It can lead to various ocular abnormalities such as Glaucoma, characterised by raised IOP, Cloudy Corneas and Vision impairment. Congenital Corneal Opacity (CCO) is rarely observed in ARS, while the exact mechanism remains unknown.

Exploring the landscape of ARS

ARS manifest through a spectrum of symptoms ranging from ocular anomalies to systemic involvement. The ocular manifestation steals the spotlight , with structural abnormalities in Anterior segment of the eye including malformation of the iris such as Polycoria, Corectopia and subsequent optic nerve damage. The characteristic histopathologic features of ARS are prominent, anterior displaced Schwalbe’s line (SL) and tissue strands connecting peripheral iris and corneal limbus. Moreover, it is observed that the abnormal SL was composed of dense collagen and ground substance covered by a layer that resembled the DM (Descemet Membrane). During the embryonic development, the NCC (neural crest cells) and mesoderm cells migrate to the area between the surface ectoderm and the optic cup, contributing to the corneal stroma and endothelium, the iris stroma, and the TM (Trabecular Meshwork). The development process of the posterior cornea and the iris are closely related, abnormalities in this process can lead to corneal opacities and anterior synechiae, these may also lead to iridocorneal adhesion .

Deciphering the Genetic code of ARS

ARS is deeply rooted in genetics , primarily following an autosomal dominant inheritance pattern. The main pathogenesis of ARS is abnormal migration and differentiation of NCC during the embryonic period , leading to multiple phenotypes of ARS. In the past , ARS was classified into 4 categories AA- Axenfeld Anomaly, AS- Axenfeld Syndrome, RA- Rieger Anomaly, RS- Rieger Syndrome. Patient was Posterior embryotoxon ( Caused by anterior displaced Schwalbe’s line  ) and peripheral  anterior adhesions were diagnosed as AA , while those with the addition of iris hypoplasia were diagnosed as RA . While patients with different other systemic defects were diagnosed as AS and RS, respectively . ARS often implicate mutations in key regulatory genes such as PITX2, FOXC1 and PAX6 (2,3)

Diagnosis

Multidisciplinary Approach :

  • Comprehensive ocular examination
  • Geneticist
  • Dentist

Imaging studies – X- rays , MRI , CT scans

Possible treatment options

  • Medications to Lower IOP and manage Glaucoma
  • Dental interventions to address orthodontic treatments or dental implants
  • Genetic counseling

Differential Diagnosis

ARS can be confused with ICE syndrome including aniridia and iridoschisis. ARS has striking clinical and histopathologic similarities with ICE but differs in being bilateral and congenital. (4,5) In ARS , the iris and angle alterations are due to retention and contraction of a primordial endothelial layer, whereas changes in ICE syndrome are secondary to migration and subsequent contraction of abnormal corneal endothelial cells.

Living with ARS

Living with ARS can present various challenges, some of the Low Vision devices that can participate in daily life are:

  • Augmented reality (AR) enabled smart glasses to superimpose improved text or images onto the user’s field of vision and thereby improving text legibility and object visibility for those with low eyesight. E.g., Google Glass and Microsoft HoloLens.
  • Adjustable contrast and magnification are two examples of customised AR apps for smartphones. Compared to specialised AR glasses, tablets and smartphones are more portable and less expensive when used with these apps.
  • Head-Mounted Displays (HMD) can be modified for AR use. HMDs are like virtual reality spectacles. They can put improved visual signals or magnified visuals right in front of the user’s eyes.
  • Text-to-Speech and Audio Feedback: AR systems can interact with text-to-speech software to narrate text that pops up in the user’s surroundings.

 

References

  1. Seifi M, Walter MA. Axenfeld-Rieger syndrome. Clin Genet. 2018 Jun;93(6):1123-1130. doi: 10.1111/cge.13148. Epub 2018 Jan 25. PMID: 28972279.
  2. Michels K, Bohnsack BL. Ophthalmological Manifestations of Axenfeld-Rieger Syndrome: Current Perspectives. Clin Ophthalmol. 2023 Mar 10;17:819-828. doi: 10.2147/OPTH.S379853. PMID: 36926528; PMCID: PMC10013571.
  3. Tümer Z, Bach-Holm D. Axenfeld–Rieger syndrome and spectrum of PITX2 and FOXC1 mutations. European Journal of Human Genetics. 2009 Dec;17(12):1527-39.
  4. Chang TC, Summers CG, Schimmenti LA, Grajewski AL. Axenfeld-Rieger syndrome: new perspectives. Br J Ophthalmol. 2012 Mar;96(3):318-22. doi: 10.1136/bjophthalmol-2011-300801. Epub 2011 Dec 23. PMID: 22199394.
  5. Shields MB. Axenfeld-Rieger syndrome: a theory of mechanism and distinctions from the iridocorneal endothelial syndrome. Transactions of the American Ophthalmological Society. 1983;81:736.

 

Submit a Comment