Korean J Ophthalmol.  2015 Aug;29(4):249-255. 10.3341/kjo.2015.29.4.249.

A Family with Axenfeld-Rieger Syndrome: Report of the Clinical and Genetic Findings

• Yang HJ
• Lee YK
• Joo CK
• Moon JI
• Mok JW
• Park MH

• KMID: 2363769
• DOI: http://doi.org/10.3341/kjo.2015.29.4.249

Abstract

PURPOSE
To describe clinical findings in a Korean family with Axenfeld-Rieger syndrome.
METHODS
A retrospective review of clinical data about patients with diagnosed Axenfeld-Rieger syndrome. Five affected members of the family underwent a complete ophthalmologic examination. We screened the forkhead box C1 gene and the pituitary homeobox 2 gene in patients. Peripheral blood leukocytes and buccal mucosal epithelial cells were obtained from seven members of a family with Axenfeld-Rieger syndrome. DNA was extracted and amplified by polymerase chain reaction, followed by direct sequencing.
RESULTS
The affected members showed iris hypoplasia, iridocorneal adhesions, posterior embryotoxon, and advanced glaucoma in three generation. None had systemic anomalies. Two mutations including c.1362_1364insCGG and c.1142_1144insGGC were identified in forkhead box C1 in four affected family members.
CONCLUSIONS
This study may help to understand clinical findings and prognosis for patients with Axenfeld-Rieger syndrome.

Keyword

Anterior segment dysgenesis; Axenfeld-Rieger syndrome; Forkhead box C1 gene

MeSH Terms

Aged, 80 and over
Anterior Eye Segment/*abnormalities/metabolism
DNA/*genetics
DNA Mutational Analysis
Eye Abnormalities/diagnosis/*genetics/metabolism
Female
Forkhead Transcription Factors/*genetics/metabolism
Genetic Testing
Homeodomain Proteins/*genetics/metabolism
Humans
Male
Middle Aged
*Mutation
Pedigree
Retrospective Studies
Transcription Factors/*genetics/metabolism
Young Adult
DNA
Forkhead Transcription Factors
Homeodomain Proteins
Transcription Factors

Figure

• 

  Fig. 1 Pedigree of the extended family. Circles represent females and squares represent males. Black symbols indicate affected individuals and white symbols indicate unaffected individuals. We performed a genetic analysis of five affected individuals (I-1, II-2, II-5, II-8, and III-2) and two other family members (II-3 and II-6). Those with a mutation are indicated with (+); the mutation is indicated with an arrow. Those without mutations are indicated with (-). Patients with the c.1362_1364insCGG mutation are indicated with an arrowhead. Patients with the c.1142_1144insGGC mutation are indicated with an arrow. NA = no amplification.

• 

  Fig. 2 (A) Patient II-8. Slit-lamp photograph of iris stromal hypoplasia with exposure of the sphincter muscle of the right eye. (B) Patient II-8. Slit-lamp photograph of iris atrophy and a defect at 10-12 o'clock in the left eye. (C) Patient II-8. Gonioscopy photographs of the iridocorneal angle showing broad iridocorneal adhesions. (D,E) Patient III-1. A physical examination revealed no facial abnormalities, including dental anomalies. (F,G) Patient III-1. A visual field examination showed a nasal step in the left eye and ring scotoma in the right eye. (H) Patient III-1. Histologic examination demonstrating iris degeneration (×100). GHT = glaucoma hemifield test; MD = mean deviation; PSD = pattern standard deviation.

• 

  Fig. 3 DNA sequence analysis of the forkhead box C1 gene. (A, C) The reference sequences derived from a normal subject are shown. (B) The sequence derived from ARS patients I-1 and II-8 shows a heterozygous mutation c.1142_1144insGGC, which results in a p.Gly379fs frameshift mutation. (D) The sequence derived from Axenfeld-Rieger syndrome patients II-5, II-8, and III-2 and from family member II-3 shows a heterozygous mutation c.1362_1364insCGG, which results in a p.Gly452fs frameshift mutation.

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