IllnessAxenfeld-Rieger syndrome, differential diagnosis

NGS +

Axenfeld-Rieger syndrome is primarily an eye disorder characterized by anomalies of the anterior segment of the eye. The iris is often irregularly developed and exhibits polycoria and/or corectopy. Corneal anomalies are also observed. About half of those affected by this syndrome develop glaucoma in late childhood or adolescence, which can lead to vision loss or even blindness. The symptoms of Axenfeld-Rieger syndrome may also include distinctive facial features such as hypertelorism, flattened midface with a broad, flat nasal bridge and a prominent forehead. The condition may eventually also be associated with microdontia or oligodontia. Less common symptoms include heart defects, hypospadias, anal stenoses and reduced growth. The three types of Axenfeld-Rieger syndrome are distinguished according to their genetic causes. Mutations in the PITX2 gene cause type 1, and mutations in the FOXC1 gene underlie type 3. Another chromosomal region that appears to be associated with type 2 in familial cases has previously been fine mapped. Affected individuals with PITX2 gene mutations are more likely than those with FOXC1 gene mutations to have other body parts affected in addition to the eyes. Axenfeld-Rieger syndrome is inherited in an autosomal dominant manner. Since the molecular genetic diagnostic yield hardly exeeds 50%, negative DNA test results do not at all question the clinical diagnosis.

Reference: https://jmg.bmj.com/content/60/4/368

• Alias: Axenfeld and Rieger anomaly
• Alias: Axenfeld anomaly
• Alias: Axenfeld syndrome
• Alias: Rieger anomaly
• Alias: Rieger syndrome
• Allelic: Angiopathy, hereditary, with nephropathy, aneurysms + muscle cramps (COL4A1)
• Allelic: Aniridia (PAX6)
• Allelic: Aortic aneurysm, familial thoracic 11, susceptibility to (FOXE3)
• Allelic: Cataract 11, multiple types (PITX3)
• Allelic: Cataract 11, syndromic, AR (PITX3)
• Allelic: Cataract 34, multiple types (FOXE3)
• Allelic: Cataract with late-onset corneal dystrophy (PAX6)
• Allelic: Coloboma of optic nerve (PAX6)
• Allelic: Coloboma, ocular (PAX6)
• Allelic: Foveal hypoplasia 1 (PAX6)
• Allelic: Glaucoma 3A, primary open angle, congenital, juvenile or adult onset (CYP1B1)
• Allelic: Hemorrhage, intracerebral, susceptibility to (COL4A1)
• Allelic: Keratitis (PAX6)
• Allelic: Microangiopathy and leukoencephalopathy, pontine, AD (COL4A1)
• Allelic: Morning glory disc anomaly (PAX6)
• Allelic: Optic nerve hypoplasia (PAX6)
• Allelic: Retinal arteries, tortuosity of (COL4A1)
• Allelic: Spinocerebellar ataxia 15 (ITPR1)
• Allelic: Spinocerebellar ataxia 29, congenital nonprogressive (ITPR1)
• Allelic: Stroke; Dandy Walker syndrome (FOXC1)
• Anterior segment dysgenesis 1, multiple subtypes (PITX3)
• Anterior segment dysgenesis 2, multiple subtypes (FOXE3)
• Anterior segment dysgenesis 3, multiple subtypes (FOXC1)
• Anterior segment dysgenesis 4; Ring dermoid of cornea (PITX2)
• Anterior segment dysgenesis 5, multiple subtypes (PAX6)
• Anterior segment dysgenesis 6, multiple subtypes (CYP1B1)
• Anterior segment dysgenesis 7, with sclerocornea (PXDN)
• Anterior segment dysgenesis 8 (CPAMD8)
• Axenfeld-Rieger anomaly with cardiac defects and/or sensorineural hearing loss (FOXC1)
• Axenfeld-Rieger syndrome, type 3, Rieger or Axenfeld anomalies (FOXC1)
• Brain small vessel disease +/- ocular anomalies (COL4A1)
• Cataract 1, multiple types (GJA8)
• Clubfoot, congenital, with/-out deficiency of long bones and/or mirror-image polydactyly (PITX1)
• Complex ocular phenotypes involving microphthalmia [panelapp] (COL4A1)
• Congenital cataracts [panelapp] (COL4A1)
• Gillespie syndrome (ITPR1)
• Iris hypoplasia + glaucoma; Iridogoniodysgenesis, type 1 (FOXC1)
• Liebenberg syndrome; Polydactyly (PITX1)
• Peters anomaly; Anterior chamber cleavage syndrome (FOXC1)
• Rieger syndrome, type 1 (PITX2)
• Sporadic aniridia [panelapp] (ITPR1)
• Structural eye disease [panelapp] (GJA8)