Axenfeld-Rieger syndrome: new perspectives: Figure 1

Abstract

Axenfeld-Rieger syndrome is a genetic disease affecting multiple organ systems. In the eye, this condition manifests with varying degrees of anterior segment dysgenesis and carries a high risk of glaucoma. Other associated systemic issues include cardiovascular outflow tract malformations, craniofacial abnormalities and pituitary abnormalities, which can result in severe endocrinological sequelae. Recent advances in molecular genetics have identified two major genes, PITX2 and FOXC1, demonstrating a wide spectrum of mutations, which aids in the molecular diagnosis of the disease, although evidence exists to implicate other loci in this condition. The management of individuals affected by Axenfeld-Rieger syndrome requires a multidisciplinary approach and would include dedicated surveillance and management of glaucoma, sensorineural hearing loss, and cardiac, endocrinological, craniofacial and orthopaedic abnormalities.

The 6p25 deletion syndrome: An update on a rare neurocristopathy

“…5,9,10 Familial ARS accounts for 70% of cases. 3 ARS is genetically heterogeneous. Heterozygous mutations in FOXC1 (Forkhead Box C1) at 6p25.3 and PITX2 (Paired-like Homeodomain 2) at 4q25 cause 16% and 10% of ARS cases, respectively (2,4,11).…”

“…1 The Axenfeld-Rieger syndrome (ARS, MIM #180500) is an umbrella term for a continuum of ASDs of NC origin, characterized by the presence of the Axenfeld or Rieger eye malformation. [1][2][3][4] The Axenfeld eye malformation consists of a prominent and anteriorly displaced Schwalbe's line (posterior embryotoxon), as present in 8-15% of the normal population, with the addition of attached iris strands. [5][6][7] The Rieger eye malformation additionally comprises iris changes including varying degrees of anterior stroma hypoplasia, corectopia (eccentric pupil) and (pseudo)polycoria (holes in pigment epithelium or anterior iris stroma, respectively).…”

“…Key clinical features comprise facial dysmorphism including mid-face and dental hypoplasia, hearing loss, short stature, skeletal abnormalities, cardiac anomalies and involuted periumbilical skin. 1,[3][4][5]8,9 ARS can occur sporadically or as familial autosomal dominant (AD) disorder without sex predominance with full penetrance but highly variable expressivity. 5,9,10 Familial ARS accounts for 70% of cases.…”

“…These malformations are present bilaterally at birth, not necessarily symmetrically, and predispose for glaucoma. [1][2][3][4][5][7][8][9] ARS is associated with a wide spectrum of additional ocular and extraocular malformations. Key clinical features comprise facial dysmorphism including mid-face and dental hypoplasia, hearing loss, short stature, skeletal abnormalities, cardiac anomalies and involuted periumbilical skin.…”

Development and Clinical Validation of a Real-Time PCR Assay for PITX2 DNA Methylation to Predict Prostate-Specific Antigen Recurrence in Prostate Cancer Patients Following Radical Prostatectomy

“…19 Mutations in PITX2 lead to Axenfeld-Rieger syndrome, a genetic disease affecting multiple organ systems. 20 However, the functional role of PITX2 during carcinogenesis is still largely unknown. Interestingly, PITX2 DNA methylation has recently been identified as an upstream regulator of the insulin-like growth factor 1 receptor and androgen receptor in prostate cancer, 21 suggesting its important role in prostate carcinogenesis and progression.…”