Familial Axenfeld‐Rieger anomaly, cardiac malformations, and sensorineural hearing loss: A provisionally unique genetic syndrome?

Abstract

Axenfeld-Rieger anomaly (ARA) is an autosomal dominant disorder of the anterior chamber of the eye that includes a prominent and anteriorly displaced Schwalbe line and an iridocorneal synechiae, and is associated with iris hypoplasia, corectopia, and hole formation. Extraocular developmental abnormalities, especially of the teeth, facial bones, and periumbilical skin, have also been reported with ARA, in the context of the so-called Axenfeld-Rieger syndrome (ARS). Genetic heterogeneity exists, as ARA maps to chromosome 6p25, whereas ARS can be linked to both chromosome 4q25 and chromosome 13q14. Here we describe a new family in which ARA is associated with cardiac malformations and sensorineural hearing loss. No abnormalities of the teeth, facial bone, or periumbilical skin, which are considered of paramount importance in the diagnosis of ARS, were observed in our patients. Genetic studies will clarify if these patients represent a unique phenotypic expression of ARS or constitute the clinical presentation of a new genetic syndrome.

Teratogenic effects of suramin on the chick embryo

“…2. JRAA was also not found among the cardiac malformations recorded in human patients with the Axenfeld-Rieger anomaly (Grosso et al 2002), which can be associated with mutations in the Pitx2gene.…”

Human p32 Is a Novel FOXC1-Interacting Protein That Regulates FOXC1 Transcriptional Activity in Ocular Cells

“…9 In rare cases, patients have congenital cardiac defects or hearing loss. 10,11 Foxc1 ϩ/Ϫ heterozygous mice have ocular defects similar to those found in patients with AR malformations. 12 Several different mechanisms underlie the impairments to FOXC1 function caused by the disease-causing mutations, including reduction in protein stability, alteration in DNA-binding specificity, alteration in nuclear localization, and defects in DNA-binding capacity and transactivation.…”

Concordant familial segregation of atrial septal defect and Axenfeld–Rieger anomaly in father and son

“…Additionally, the coexistence of ASD, Axenfeld-Rieger anomaly and sensorineural hearing loss was detected by Cunningham et al (1998) in multiple members of a single family, supporting an autosomal dominant inheritance of a specific disease. Grosso et al (2002) described a similar family presenting with Axenfeld-Rieger anomaly, CHD and sensorineural hearing loss. Nevertheless, ASD was not present in these patients, as CHD consisted in tricuspid and mitral defects.…”