Axenfeld-Rieger syndrome

Key points of this disease

• Axenfeld-Rieger syndrome (ARS) is a congenital anterior segment dysgenesis caused by abnormal migration and differentiation of neural crest cells, showing autosomal dominant inheritance.
• During late embryonic development, the normal regression of undifferentiated endothelial cells covering the anterior chamber is impaired, leading to ocular findings such as posterior embryotoxon, iris hypoplasia, and corectopia.
• Systemic abnormalities including dental anomalies, facial bone abnormalities, and redundant periumbilical skin may be present, and cataract or lens dislocation may also occur.
• Glaucoma complicates approximately 50–60% of cases, and early intraocular pressure management directly affects visual prognosis.
• The main causative genes are PITX2 (type 1) and FOXC1 (type 3), which together account for 40–70% of all cases.
• In FOXC1 mutations, attention should be paid to complications such as corneal opacity, neurological abnormalities (white matter lesions), and cardiovascular anomalies.
• Surgery is required when intraocular pressure cannot be controlled with medication. Treatment follows that for primary congenital glaucoma, but surgical success rates are somewhat lower.

1. What is Axenfeld-Rieger syndrome?

Axenfeld-Rieger syndrome (ARS) is a group of congenital disorders combining anterior segment dysgenesis and systemic abnormalities. The fundamental etiology is thought to be abnormal migration and differentiation of neural crest cells. During late embryonic development, the normal regression of undifferentiated endothelial cells covering the anterior chamber from the iris and angle is impaired, and their remnants cause strand formation and high iris insertion.

Historical background: In 1920, Axenfeld described posterior embryotoxon (anterior displacement and thickening of Schwalbe’s line) and iris strands. In 1934–1935, Rieger additionally reported iris hypoplasia, corectopia, and polycoria. Currently, it is classified into the following three stages.

• Axenfeld anomaly: Peripheral iris strands adhere to a thickened and anteriorly displaced Schwalbe’s line (posterior embryotoxon).
• Rieger anomaly: Additionally, iris stromal hypoplasia presents with corectopia, ectropion uveae, and pseudopolycoria.
• Rieger syndrome (ARS): Accompanied by systemic abnormalities such as dental anomalies and facial bone abnormalities.

These are collectively referred to as Axenfeld-Rieger syndrome. Glaucoma complicates 50–60% of cases, and it is usually bilateral with autosomal dominant inheritance. Cataract and lens dislocation are also frequently associated.

Epidemiology: The prevalence has been reported as approximately 1/200,000, but recent estimates suggest 1/50,000 to 1/100,000 ²⁾⁴⁾. There is no sex predilection, and it is often diagnosed in infancy.

Genetic classification is as follows:

ARS type 1

Causative gene: PITX2 (4q25)

Main features: Anterior segment anomalies, dental anomalies, redundant periumbilical skin/omphalocele, craniofacial anomalies, cardiovascular anomalies

ARS type 2

Causative gene: 13q14 (not yet identified)

Main features: Anterior segment anomalies, glaucoma. Systemic anomalies are less frequent than in types 1 and 3

ARS type 3

Causative gene: FOXC1 (6p25)

Main features: Anterior segment anomalies, glaucoma, sensorineural hearing loss, atrial septal defect, renal anomalies, white matter lesions

FOXC1 and PITX2 mutations account for 40–70% of ARS cases ⁵⁾. However, the causative gene remains unidentified in 60% of ARS cases ⁴⁾, indicating substantial genetic heterogeneity.

In a large registry analysis of 506 cases of childhood- and young adult-onset glaucoma, the overall molecular diagnostic rate was 24.7% (125/506 cases) ¹¹⁾. A diagnostic rate of 56.5% was limited to the subgroup of glaucoma associated with non-acquired ocular anomalies ¹¹⁾. Among cases with a genetic diagnosis, CYP1B1 (23.2%), MYOC (19.2%), and FOXC1 (16.8%) were most common, with the genetic composition varying by study population ¹¹⁾.

Q How are ARS types 1, 2, and 3 distinguished?

A

They are distinguished by the causative gene. Type 1 is caused by PITX2 (4q25) mutations and is associated with dental, umbilical, and facial bone anomalies. Type 3 is caused by FOXC1 (6p25) mutations and is associated with hearing loss, cardiac defects, renal anomalies, and neurological abnormalities. Type 2 maps to 13q14 but the causative gene has not been identified; it primarily involves anterior segment anomalies and glaucoma. Identification of a pathogenic variant aids in genetic confirmation and classification, but a negative result does not exclude ARS ¹⁰⁾.

2. Main Symptoms and Clinical Findings

Gong X, Lei X, Li Z, et al. Identification and functional study of a novel FOXC1 missense mutation in a Chinese family with Axenfeld-Rieger syndrome. Sci Rep. 2025;15(1):19957. Figure 1. PMID: 40481210; PMCID: PMC12144153; DOI: 10.1038/s41598-025-04872-x. License: CC BY 4.0. https://creativecommons.org/licenses/by/4.0/

Panel A shows the pedigree of an ARS family; Panel B shows anterior segment photographs of both eyes (OD/OS). Yellow arrows indicate posterior embryotoxon distributed circumferentially at the limbus, and blue arrows indicate iridocorneal adhesions with iris atrophy and hole formation.

Subjective Symptoms

• Photophobia (glare): Caused by light scattering due to iris abnormalities and pseudopolycoria. May worsen with age.
• Visual impairment: Becomes prominent when glaucoma progresses.
• May be asymptomatic: Infants and young children cannot report symptoms, and the condition is often discovered during health checkups or incidentally.

Clinical Findings

Major ocular findings are listed below.

Ocular Finding	Characteristics
Posterior embryotoxon	Anterior displacement and thickening of Schwalbe’s line
Iris processes	Fine thread-like to broad band-like
Pupil deviation	Deviation away from posterior embryotoxon
Pseudopolycoria	Perforation-like appearance of iris stroma
Uveal ectropion	Eversion of iris pigment epithelium

Posterior embryotoxon is a remnant of undifferentiated cells at the Schwalbe line, appearing as a linear opacity along the limbus, 0.5–2.0 mm central to the limbus. It is often partial rather than circumferential. Adhesion between the prominent Schwalbe line and the iris is called Axenfeld anomaly, and when accompanied by iris stromal atrophy, it is called Rieger anomaly.

The cornea is usually clear with normal endothelial structure, but secondary corneal opacity may occur due to physical contact with residual tissue. Corneal opacity is often limited to the periphery and generally does not directly affect vision. However, in FOXC1 mutations, corneal opacity and corneal neovascularization are more pronounced, and the degree of corneal abnormality is greater and glaucoma is more frequent compared to PITX2 mutations¹⁾.

Angle findings include high iris insertion, persistent uveal strands, and thickened Schwalbe line (posterior embryotoxon). Cases with spherophakia and lens subluxation have also been reported⁷⁾.

Glaucoma occurs in 50–60% of cases. Intraocular pressure elevation may occur in infancy, but most cases develop in childhood to young adulthood. Some cases are diagnosed after progressive vision loss, so it is important not to overlook anterior segment findings and glaucomatous changes⁶⁾.

In a 7-year-old boy reported by Li et al. (2021) (ARS type 3, de novo FOXC1 mutation), corneal diameter was 14 mm, axial length 27.16/26.56 mm, cup-to-disc ratio 0.9, and IOP 33/20 mmHg. Bilateral glaucoma surgery was required from 36 days after birth⁵⁾.

Systemic findings are as follows:

• Craniofacial dysmorphism: hypertelorism, increased inner canthal distance, maxillary hypoplasia (saddle nose), broad flat nasal bridge, thin upper lip, prominent lower lip³⁾
• Dental abnormalities: microdontia, oligodontia, missing teeth, enamel prone to caries¹⁾
• Excess periumbilical skin/umbilical hernia: redundant skin around the umbilicus is characteristic⁸⁾
• Cardiovascular abnormalities: Atrial septal defect, heart valve abnormalities⁵⁾²⁾
• Sensorineural hearing loss: Especially in FOXC1 mutations (type 3)²⁾⁴⁾
• Pituitary abnormalities / growth hormone deficiency
• Cataract / lens dislocation

Q What is the probability of glaucoma complicating ARS?

A

Approximately 50–60% of ARS cases are complicated by glaucoma. It often develops from childhood to young adulthood, but some cases present with elevated intraocular pressure in infancy. Regular intraocular pressure measurement and optic nerve evaluation are necessary; for details, see the “Standard Treatment” section.

3. Causes and Risk Factors

ARS mainly shows autosomal dominant inheritance, but penetrance and clinical presentation vary¹⁰⁾. Even within the same family carrying the same gene mutation, significant individual differences (variable expressivity) in clinical features can occur¹⁾.

Main causative genes

• PITX2 (4q25): Causative gene for type 1. A paired-like homeodomain transcription factor involved in the development of the eye, teeth, and abdominal wall organs³⁾. Individuals with PITX2 mutations are often identified as having ARS, and they tend to develop glaucoma later than those with FOXC1 mutations⁹⁾.
• FOXC1 (6p25): Causative gene for type 3. A forkhead box transcription factor involved in the development of the eye, heart, kidney, and brain⁵⁾²⁾. Previously reported as FKHL7¹²⁾, with over 80 mutations described⁵⁾. Individuals with FOXC1 mutations are more likely to develop glaucoma at a younger age than those with PITX2 mutations, and may be identified as having congenital glaucoma in infancy⁹⁾.
• PAX6 (11p13): Known to be associated with aniridia.
• FOXO1A (13q14): Candidate gene for type 2.
• CYP1B1: Some ARS cases with mutations have been reported.

In large cohort studies, FOXC1 and PITX2 mutations were associated with a broad spectrum of glaucoma from childhood to adulthood⁹⁾. Cases initially diagnosed clinically as PCG (primary congenital glaucoma) may be reclassified by genetic testing, and genetic testing contributes to accurate disease classification when anterior segment findings in infants are subtle.

Developmental Delay and Microdeletions

In cases with microdeletions around the PITX2 gene, overlapping deletions of NEUROG2, UGT8, and NDST4 can lead to developmental delay and intellectual disability⁸⁾³⁾.

Kawanami et al. (2023) reported a 3-year-old Japanese boy with a 2.5 Mb microdeletion at 4q25 (including PITX2, NEUROG2, and ANK2). He presented with umbilical hernia, iris coloboma, and developmental delay, but his electrocardiogram was normal despite the ANK2 deletion. Haploinsufficiency of NEUROG2 was considered a candidate cause of developmental delay⁸⁾.

Genetic Counseling

ARS is inherited in an autosomal dominant manner, so the chance of passing the mutation from an affected parent to a child is 50%. However, the severity of symptoms varies even within the same family. If you are considering pregnancy or have a family member with ARS, we recommend consulting a genetic specialist.

Q If a parent has ARS, what is the probability of passing it to a child?

A

Due to autosomal dominant inheritance, the probability of transmission from an affected parent is 50%. Penetrance and phenotype are variable; even with the same mutation, the presence and severity of symptoms can differ¹⁾¹⁰⁾. Genetic testing and genetic counseling are recommended.

4. Diagnosis and Examination Methods

Clinical Diagnosis

The diagnosis of ARS is based on a combination of bilateral anterior segment anomalies centered on the angle and iris. Posterior embryotoxon is seen in many cases but is not essential for diagnosis¹⁰⁾. In cases where posterior embryotoxon is not visible on slit-lamp microscopy, angle abnormalities are assessed by gonioscopy. If systemic abnormalities are present, referral to relevant departments such as dentistry, cardiology, and neurology is indicated as ARS syndrome, and in pediatric cases, a full systemic workup is performed in collaboration with pediatrics^10,13).

Posterior embryotoxon alone is not specific to ARS; therefore, it should be evaluated together with iris and angle findings, glaucoma, systemic findings, and family history¹³⁾.

In the classification system for childhood glaucoma in the Glaucoma Clinical Practice Guidelines (5th edition), ARS is positioned as a representative example of glaucoma associated with congenital ocular anomalies¹³⁾. It is diagnosed when ocular anomalies present at birth meet the diagnostic criteria for childhood glaucoma.

Genetic Testing

• Next-generation sequencing (NGS) panel testing is used⁵⁾
• Whole genome sequencing (WGS) can also detect large deletions and complex rearrangements³⁾
• Genetic testing is important for differentiating atypical cases and Chandler syndrome¹⁾
• Infants with FOXC1 mutations may initially be diagnosed with primary congenital glaucoma (PCG)⁹⁾, and genetic testing enables accurate disease classification

Differential Diagnosis

The main diseases to be differentiated from ARS are shown below.

Disease	Differences from ARS
ICE syndrome	Unilateral, acquired, female predominance
Peters anomaly	Central corneal opacity, Descemet membrane defect
Aniridia	Corneal pannus, foveal hypoplasia
Posterior polymorphous corneal dystrophy	Bilateral, familial, no sex difference

ICE syndrome (progressive iris atrophy, Chandler syndrome, etc.) is important to differentiate from ARS, but the key distinguishing point is that ICE is unilateral and acquired, whereas ARS is bilateral and congenital.

Caution against misdiagnosis as Chandler syndrome

Cases of ARS misdiagnosed as Chandler syndrome have been reported. Bilateral Chandler syndrome is rare; therefore, when bilateral and congenital iris abnormalities are observed, ARS should be actively considered in the differential diagnosis, and genetic testing is recommended ¹⁾.

5. Standard treatment

There is currently no curative treatment for ARS itself; management focuses on glaucoma control and surveillance for systemic complications. The treatment strategy follows that for early-onset developmental glaucoma (primary congenital glaucoma: PCG) ¹³⁾.

Pharmacological treatment

Glaucoma complicates approximately 50–60% of ARS cases. Pharmacological treatment follows that for general glaucoma, but it is often ineffective.

Aqueous humor suppressants

Beta-blockers: One of the drugs used in pediatric glaucoma. Selection should consider age, systemic condition, and contraindications ¹³⁾.

Carbonic anhydrase inhibitor (CAI) eye drops: e.g., brinzolamide. Can be used in combination with beta-blockers.

Alpha-2 agonists (brimonidine): Contraindicated in children under 2 years of age due to neuropsychiatric symptoms (apnea, bradycardia, hypotension, hypotonia, central nervous system depression) ¹³⁾.

Aqueous humor outflow enhancers

Prostaglandin-related drugs: e.g., latanoprost, travoprost. Their efficacy in children is considered weaker than in adults ¹³⁾.

Example: A 7-year-old boy was managed long-term with travoprost + brinzolamide ⁵⁾. In a 77-year-old man, IOP remained 35 mmHg despite latanoprost/timolol + brinzolamide, indicating poor control ²⁾.

There is a report that there is no difference in efficacy between prostanoid FP receptor agonists and beta-blockers ¹³⁾.

In infants and young children, the dose of eye drops is relatively large compared to body weight and body surface area, so the lowest concentration possible should be used ¹³⁾.

Surgical Treatment

If intraocular pressure cannot be controlled with medication, surgery is performed ¹⁰⁾¹³⁾.

• Angle surgery (goniotomy/trabeculotomy): First choice if the angle is open and the trabecular meshwork coverage by peripheral anterior synechiae (PAS) is not extensive. Selecting a site with less PAS for incision increases the success rate. However, the success rate is lower than for PCG ¹³⁾.
• Trabeculectomy (with mitomycin C): Considered in cases where intraocular pressure cannot be controlled with angle surgery or other methods. In children, the surgical technique and follow-up should be individually determined, taking into account postoperative scarring and long-term complications ¹⁰⁾¹³⁾.
• Glaucoma drainage device (GDD): May be the first choice when angle surgery is ineffective ¹³⁾. In a meta-analysis of pediatric glaucoma, the success rate was 87% at 12 months, 77% at 24 months, and 54% at 48 months ¹⁴⁾. Mean postoperative IOP was 16.5 mmHg at 12 months and 17.6 mmHg at 24 months ¹⁴⁾.
• Cyclodestructive procedures: Last resort for refractory cases. Success rates are low, and the need for retreatment and complication rates are high.
• Micropulse cyclophotocoagulation: A report exists of IOP control achieved in a child with ARS and PITX2 deletion ³⁾.

Reported complications after GDD surgery include shallow anterior chamber 13.6%, hypotony 11.7%, choroidal effusion 8.3%, and endophthalmitis 1.7% ¹⁴⁾.

Chakraborty et al. (2022) reported a case of ARS-associated retinal detachment (15-year-old boy). The patient had microspherophakia and lens subluxation; after vitrectomy, IOP rose to 41 mmHg and a staphyloma formed. Diode cyclophotocoagulation was performed, and final IOP was 18 mmHg ⁷⁾.

Other Management

• Refractive correction: Corneal astigmatism and hyperopia may be severe; refractive correction with glasses or other means is performed. Corneal opacity is usually limited to the periphery and does not affect vision.
• Tinted contact lenses: Effective for reducing photophobia due to iris atrophy and polycoria
• Prevention of amblyopia: Regular ophthalmic management from childhood is necessary
• Penetrating keratoplasty (PKP): Performed to improve visual acuity in cases of severe corneal opacity due to FOXC1 mutation¹⁾
• Multidisciplinary surveillance: Requires specialized follow-up for glaucoma, hearing loss, cardiac disease, endocrine disorders, dentistry, and craniofacial issues⁵⁾

Precautions in pediatric glaucoma management

Brimonidine (alpha-2 agonist) eye drops are contraindicated in infants under 2 years of age¹³⁾. Glaucoma in ARS is often refractory, and surgery is considered in cases where long-term management with medication alone is not possible. In pediatric glaucoma surgery, it is important to explain the possibility of reoperation and long-term complications, and to provide continuous follow-up¹⁰⁾¹³⁾.

Q What is the success rate of glaucoma surgery associated with ARS?

A

A reliable success rate specific to ARS has not been established, and outcomes vary depending on age, angle dysgenesis, and prior surgery. The success rate of angle surgery is considered lower than that of primary congenital glaucoma¹³⁾. In a meta-analysis of pediatric glaucoma overall (not limited to ARS), the estimated success rate of GDD was 87% at 12 months and 77% at 24 months, but there was heterogeneity among disease groups and study conditions¹⁴⁾. Refractory cases may require multiple surgeries.

6. Pathophysiology and detailed pathogenesis

Neural crest cell abnormalities

The fundamental etiology of ARS is a defect in neural crest cell migration and differentiation. Impaired development of neural crest cells in the anterior chamber, anterior chamber angle, facial bones, teeth, cardiovascular system, and periumbilical skin leads to multisystem malformations.

In late embryonic stages, the undifferentiated endothelial cells covering the anterior chamber normally disappear from the iris and angle. In ARS, this disappearance process is impaired, and undifferentiated endothelial cells persist on the iris, causing strand formation. In the angle, high iris insertion occurs, mechanically covering the trabecular meshwork.

Histologically, a monolayer of endothelial-like cells with a Descemet-like membrane abnormally extends from the posterior cornea to the anterior chamber, angle, and iris surface. The membrane is present in quadrants with ectropion uveae and corectopia, while iris atrophy is observed in the opposite quadrants.

Functions of FOXC1 and PITX2

FOXC1 and PITX2 are both transcription factors that bind to specific DNA sequences to regulate the expression of downstream genes. They act synergistically in anterior segment development and regulate common downstream target genes³⁾. The forkhead domain (a 110-amino acid DNA-binding domain) of FOXC1 is functionally most important²⁾, and mutations in this domain have been suggested to be more strongly associated with neuropsychiatric symptoms.

Pathogenesis of Glaucoma

The following two mechanisms have been identified for intraocular pressure elevation:

• Mechanical obstruction due to anterior synechia of the iris: High iris insertion mechanically covers the trabecular meshwork. Eyes with higher iris insertion are more likely to be associated with glaucoma.
• Angle dysgenesis: Developmental abnormalities of the aqueous humor outflow pathway, including Schlemm’s canal and the trabecular meshwork. The juxtacanalicular connective tissue is thickened and present beneath Schlemm’s canal, occupying the intercellular spaces of the trabecular meshwork and impairing aqueous humor outflow.

The degree of iris coloboma and the amount of angle iris processes do not necessarily correlate with glaucoma severity. However, a high degree of iris synechia in the angle predisposes to glaucoma.

FOXC1 mutations promote congenital glaucoma more than other mutations¹⁾, and morphological abnormalities of the ciliary body and drainage angle may contribute to IOP elevation¹⁾.

FOXC1 Mutations and Corneal Abnormalities

In FOXC1 mutant mice, decreased collagen fibers and structural abnormalities in the corneal stroma, as well as impairment of keratocytes, are observed¹⁾. Furthermore, FOXC1 functions as a suppressor of corneal angiogenesis (via regulation of VEGF bioavailability)¹⁾, and loss of this suppression due to FOXC1 mutation leads to corneal neovascularization.

FOXC1 Mutations and Neurological Abnormalities

FOXC1, as a FOX family transcription factor, also plays an important role in brain development⁴⁾.

In a systematic review, white matter abnormalities were reported in 26 of 63 reports (41.3%). However, 60 reports were case reports or case series, and the patient-level prevalence cannot be estimated from this proportion¹⁵⁾. FOXC1 mutations may be associated with cerebral small vessel disease (CSVD), white matter hyperintensities, enlarged perivascular spaces, microbleeds, and lacunar infarcts.

Ohkubo et al. (2025) confirmed periventricular white matter lesions, enlarged perivascular spaces, and tortuous dilation of the vertebrobasilar artery on brain MRI in a 2-year-old Japanese boy (FOXC1 mutation: c.240del, p.Y81Ifs21). His father had a history of cerebral infarction at age 18⁴⁾.

In a review of 95 FOXC1 mutation cases, 6.3% had neuropsychiatric symptoms (learning difficulties, epilepsy, intellectual disability, delusional jealousy, etc.), and 83.3% of cases with forkhead domain mutations exhibited neuropsychiatric symptoms²⁾.

Q Can brain abnormalities occur in ARS?

A

Yes. ARS with FOXC1 mutations has been reported with white matter abnormalities. In a systematic review, 26 of 63 reports described such findings, but patient-level prevalence could not be estimated¹⁵⁾. FOXC1 mutations have been suggested to be associated with cerebral small vessel disease and stroke risk, and neurological evaluation based on symptoms and family history is considered.

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7. Latest Research and Future Perspectives (Investigational Reports)

For Patients: Please Read Carefully

The following content is currently at the research or clinical trial stage and is not standard treatment available at general hospitals. This is reference information for experts regarding future medical developments.

Identification of Novel Genetic Mutations

In recent years, many novel mutations have been reported through next-generation sequencing and whole-genome sequencing.

Wowra et al. (2024) identified a large deletion (novel mutation) involving part of FOXC1 exon 1 and the entire 3’UTR in three Polish sisters with ARS. The phenotype varied greatly within the same family, and they were initially misdiagnosed with Chandler syndrome¹⁾.

Jiang et al. (2024) identified a complex genomic rearrangement in a Chinese family with ARS type 1, including a 6.15 Mb deletion of chromosome 4q25 involving PITX2, a 45.71 Mb inversion, and a 14 bp deletion. An 11-year-old girl presented with IOP of 43.5/44.0 mmHg³⁾.

Other novel mutation reports include FOXC1 p.Phe136Leu (forkhead domain)²⁾, FOXC1 p.S82R (de novo mutation)⁵⁾, and FOXC1 c.240del, p.Y81Ifs21⁴⁾.

Elucidation of Mechanisms Underlying Neuropsychiatric Symptoms

Yoshino et al. (2024) reported a case of ARS type 3 in a 77-year-old Japanese man. Delusional jealousy appeared at age 72, and leukoencephalopathy was confirmed. A literature review of 95 cases with FOXC1 mutations found neuropsychiatric symptoms in 6.3% (6/95 cases), of which 83.3% (5/6 cases) had forkhead domain mutations²⁾.

This finding suggests that the functional domain of FOXC1 mutations may be involved in the development of neuropsychiatric symptoms, indicating the importance of long-term follow-up from a mental health perspective.

Cerebrovascular Risk and Prevention

It has been suggested that FOXC1 mutations may induce CSVD and increase the risk of stroke⁴⁾. The importance of prevention and early intervention for neurovascular diseases in ARS patients is considered a future research topic.

Corneal Pathology and Prospects for Novel Treatments

The pathogenesis of corneal “sclerocornea” due to FOXC1 mutations is being elucidated¹⁾. Understanding the molecular mechanisms of corneal opacity is expected to lead to the development of novel treatments using gene therapy, anti-fibrotic drugs, and biomaterials¹⁾.

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8. References

1. Wowra B, Wysocka-Kosmulska M, Stanienda-Sokół K, et al. Diagnostic Challenges of Axenfeld-Rieger Syndrome and a Novel FOXC1 Gene Mutation in a Polish Family. J Clin Med. 2024;13(19):5761. doi:10.3390/jcm13195761.
2. Yoshino Y, Iga JI, Ueno SI.. A Novel Mutation of FOXC1 (P136L) in an Axenfeld-Rieger Syndrome Patient With a Systematized Delusion of Jealousy: A Case Report and Literature Review. Mol Genet Genomic Med. 2024;12(11):e70008. doi:10.1002/mgg3.70008. PMID:39520097; PMCID:PMC11549375.
3. Jiang Z, Zhang Y, Wang L, Yang H, Yu L. Complex genomic rearrangement with deletion of PITX2 in a Chinese family with Axenfeld-Rieger syndrome: A case report and literature review. Molecular vision. 2024;30:466-476. PMID:39959165; PMCID:PMC11829790.
4. Ohkubo Y, Hayashi T, Ida K, Nakano E, Hamada A, Higashida T, et al. A case of Axenfeld-Rieger syndrome with neuroradiological abnormalities. Radiology case reports. 2025;20(10):5078-5080. doi:10.1016/j.radcr.2025.06.072. PMID:40741157; PMCID:PMC12310057.
5. Li K, Tang M, Xu M, Yu Y. A novel missense mutation of FOXC1 in an Axenfeld-Rieger syndrome patient with a congenital atrial septal defect and sublingual cyst: a case report and literature review. BMC Med Genomics. 2021;14:255. doi:10.1186/s12920-021-01103-w.
6. Khan TA, Zahid MA, Akram A, Rauf A. Progressive Vision Loss in a Patient With Axenfeld-Rieger Syndrome. Cureus. 2022;14(5):e25128. doi:10.7759/cureus.25128.
7. Chakraborty D, Basak SK, Saha A, Mondal S, Mitra A. A case of Axenfeld-Rieger syndrome with retinal detachment. Indian journal of ophthalmology. 2022;70(7):2650-2652. doi:10.4103/ijo.IJO_2737_21. PMID:35791188; PMCID:PMC9426138.
8. Kawanami Y, Horinouchi T, Morisada N, Kato T, Nozu K. 4q25 Microdeletion with Axenfeld-Rieger Syndrome and Developmental Delay. Case reports in genetics. 2023;2023:4592114. doi:10.1155/2023/4592114. PMID:36816813; PMCID:PMC9935865.
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10. Michels K, Bohnsack BL. Ophthalmological Manifestations of Axenfeld-Rieger Syndrome: Current Perspectives. Clin Ophthalmol. 2023;17:819-828. doi:10.2147/OPTH.S379853. PMID:36926528; PMCID:PMC10013571.
11. Knight LSW, Ruddle JB, Taranath DA, et al. Childhood and Early Onset Glaucoma Classification and Genetic Profile in a Large Australasian Disease Registry. Ophthalmology. 2021;128(11):1549-1560. doi:10.1016/j.ophtha.2021.04.016. PMID:33892047.
12. Mirzayans F, Gould DB, Héon E, Billingsley GD, Cheung JC, Mears AJ, et al. Axenfeld-Rieger syndrome resulting from mutation of the FKHL7 gene on chromosome 6p25. European journal of human genetics : EJHG. 2000;8(1):71-4. doi:10.1038/sj.ejhg.5200354. PMID:10713890.
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14. Stallworth JY, O’Brien KS, Han Y, Oatts JT. Efficacy of Ahmed and Baerveldt glaucoma drainage device implantation in the pediatric population: A systematic review and meta-analysis. Surv Ophthalmol. 2023;68(4):578-590. doi:10.1016/j.survophthal.2023.01.010. PMID:36740196; PMCID:PMC10293048.
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