eMedicine Specialties > Ophthalmology > Genetic Disorders

Peters Anomaly

Guruswami Arunagiri, MD, FRCS, Department of Ophthalmology, Permanente Medical Group, Sacramento, CA

Updated: Feb 20, 2009

Introduction

Background

Peters anomaly is a rare form of anterior segment dysgenesis in which abnormal cleavage of the anterior chamber occurs. Involving the central or entire cornea, Peters anomaly is divided into 2 types depending on whether or not the lens is abnormal. Peters anomaly may have an inherited pattern. Mutations involve the PAX6 gene.^{[1 ]}Peters anomaly may also be associated with other ocular or systemic abnormalities.

Pathophysiology

In Peters anomaly, central or paracentral corneal opacity is present. In some cases, this opacity may involve the entire cornea. In type 1, the lens may or may not be cataractous; however, the lens does not adhere to the cornea. In type 2, the lens is cataractous and adheres to the cornea.^{[2,3 ]}

Peters anomaly may be associated with other abnormalities of the eye, including myopia, aniridia, coloboma of the iris, choroid, microphthalmos, persistent hyperplasia of primary vitreous (PHPV), and optic disk hypoplasia.

Systemic associations with Peters anomaly include trisomy 13-15, partial deletion of chromosome arm 11q, and Norrie disease. In Krause-Kivlin syndrome, the patient is of short stature with developmental delay and facial dysmorphism. Peters plus syndrome is characterized by genitourinary abnormalities; syndactyly; brachycephaly; and cardiac, neural, and hearing abnormalities.^{[4 ]}Bilateral Peters anomaly was reported in an infant with 49XXXXY syndrome.

Frequency

United States

The incidence rate in the United States is unknown (very rare).

International

The incidence rate throughout the world is unknown (very rare).

Mortality/Morbidity

In addition to corneal opacity and cataract, glaucoma may increase morbidity.

Mortality may be increased because of other systemic involvement, especially cardiac anomalies.

Race

Peters anomaly occurs in all races. No known racial predilection exists.

Sex

No known sexual predilection exists.

Age

Peters anomaly is manifested in utero during the first trimester of pregnancy (10-16 wk) and, therefore, is noted at birth. The anterior segment is formed completely by the 10th week, and, by the 16th week, most of the Descemet membrane is formed.

Clinical

History

Because the ocular abnormalities are noted at birth, the obstetrician or the pediatrician is the first to observe them. The child may be completely asymptomatic or may have other ocular or systemic anomalies.

Physical

Central, paracentral, or complete corneal opacity is always present in patients with Peters anomaly. Usually, no vascularization of this opacity occurs, which helps in distinguishing it from other causes of congenital corneal opacity.^{[5,2,6 ]}

In type 1, 80% of cases are bilateral. Central or paracentral annular corneal opacity is present. The surrounding peripheral cornea may be clear or edematous because of glaucoma. The cornea is avascular. Iris strands often extend from the collarette, across the anterior chamber, to the posterior surface of the cornea. These may be filamentous or thick strands or sheets. The opacity is caused by a defect in the underlying corneal endothelium and the Descemet membrane. The lens may be clear or cataractous.
In type 2, cases are usually bilateral. The corneal opacity is denser and may be central or eccentric. The lens is usually cataractous and typically is juxtaposed to the cornea. The posterior stroma, the Descemet membrane, and the endothelium are defective. Iris strands may or may not be present. Other ocular and systemic abnormalities are more common in type 2 than in type 1.
Other ocular abnormalities: Peters anomaly may be associated with microcornea, cornea plana, sclerocornea aniridia, and glaucoma due to dysgenesis of the angle. Glaucoma occurs in up to 90% of cases. Colobomas of the iris and the choroid, as well as PHPV, have been reported. Optic nerve hypoplasia or atrophy also can occur. One case of Goldenhar syndrome with Peters anomaly has been reported.^{[7 ]}
Systemic abnormalities
- Peters anomaly is seen in trisomy 13-15, ring chromosome 21^{[8 ]}, Norrie disease, partial deletion of chromosome arm 11q, mosaic trisomy 9, and 49XXXXY syndrome.
- Systemic associations in Peters anomaly include developmental delay, congenital heart disease, structural defects of the neurologic system, spinal defects, genitourinary abnormalities, external ear abnormalities, hearing loss, cleft lip and palate, and short stature.
Krause-Kivlin syndrome is an autosomal recessive condition with short stature, facial dysmorphism, developmental delay, and delayed skeletal maturation.^{[9 ]}
Peters plus syndrome also is an autosomal recessive condition. Clinical manifestations include brachycephaly, brain malformation, cardiac anomalies, genitourinary anomalies, syndactyly, cleft lip and palate, and hearing abnormalities.^{[4,10,11,12 ]}

Causes

The cause of Peters anomaly is unknown; it may be caused by genetic factors, environmental factors, or both. The critical event must occur in the first trimester of pregnancy during the formation of the anterior chamber.

Most cases of Peters anomaly are sporadic or autosomal recessive. They are rarely autosomal dominant.

The PAX6 gene is involved in ocular embryogenesis. This gene seems to regulate other genes that also are involved in ocular development by impairing paired box sequence within a gene. Mutations in the PAX6 gene have been detected in various ocular anomalies, including Peters anomaly, aniridia, Axenfeld anomaly, and autosomal dominant keratitis characterized by corneal opacification and vascularization.^{[1,13 ]}Because some studies have found no mutation of the PAX6 gene in a large cohort of patients with Peters anomaly, other unidentified mutations also may cause Peters anomaly.^{[14 ]}
The RIEG1 gene is associated with Reiger syndrome. This gene is located on band 4q25. A case of Peters anomaly has been reported with mutation of this gene.^{[15 ]}
Another case of Peters anomaly was associated with abnormal centromere-chromatid apposition.^{[16 ]}

Differential Diagnoses

Cataract, Congenital
Corneal Graft Rejection
Glaucoma, Secondary Congenital
Posterior Polymorphous Corneal Dystrophy

Workup

Laboratory Studies

Peters anomaly is a clinical diagnosis. Depending on the physical examination, laboratory studies may be warranted.
The only specific test for Peters anomaly is histopathology of the cornea (see Histologic Findings).

Imaging Studies

The following imaging studies may be performed based on the clinical findings from the physical examination:
- MRI
  - MRI of the brain and the spinal cord are indicated to rule out neurologic defects.
  - MRI of the abdomen is indicated to rule out genitourinary abnormalities.
- Echocardiogram (ECHO) is indicated to rule out cardiac defects.
- Ocular ultrasonogram
  - Ocular ultrasonogram is a useful tool to help diagnose Peters anomaly and to differentiate it from other causes of corneal opacity.
  - Ocular ultrasonogram is also helpful in assessing associated anterior segment abnormalities.^{[17 ]}
  - Ocular ultrasonogram shows hypoechogenicity of the anterior stroma that histopathologically correlates with the absence of the Bowman layer and the presence of stromal edema.^{[17 ]}

Other Tests

To rule out hearing abnormalities, hearing tests may be performed.

Procedures

A thorough ocular examination is done under anesthesia.
External photographs, ocular ultrasonogram (see Imaging Studies), intraocular pressure, and retinoscopy may also be performed.

Histologic Findings

Histopathology is often diagnostic. Histologic findings show either thinning or absence of the Descemet membrane or the endothelium. The lens may be normal, or it may be cataractous and adhere to the cornea. The stromal lamellae are irregular and more closely packed. Undifferentiated iris strands attach to the posterior surface of the cornea.

Histochemical studies have shown absence of keratan sulfate in both the cornea and the sclera.

Immunohistochemical studies have shown increased amounts of fibronectin and type VI collagen in the corneas of patients with Peters anomaly.^{[18,19 ]}

Treatment

Medical Care

General
- In a child suspected of having Peters anomaly, a thorough physical examination by a pediatrician is warranted.
- Genetic counseling must be offered as needed.
Ocular
- Glaucoma is very common in patients with Peters anomaly, occurring in up to 90% of them. No Food and Drug Administration (FDA)-approved medications are available for the treatment of glaucoma in children.
- A pediatric glaucomatologist best manages these patients.

Surgical Care

For patients with a clear peripheral cornea, peripheral optical iridectomy may be performed.
For patients with bilateral visually disabling corneal opacity, penetrating keratoplasty is recommended. To prevent amblyopia, the earlier the surgery is performed (eg, before 3-6 mo), the better the results. The rates of graft clarity are between 20-60% in different studies.^{[20,21,22,23,24,25,26 ]}
For patients with cataract, lensectomy/vitrectomy is indicated. If left aphakic, these patients will require aphakic contact lenses or aphakic spectacles.
Filtration surgery, cryoablation, or a tube shunt may be required for those patients with glaucoma whose increased intraocular pressure cannot be managed by medications.^{[27 ]}

Consultations

Pediatrician - Thorough examination to rule out other systemic abnormalities
Geneticist - Genetic counseling
Pediatric glaucomatologist - Management of glaucoma (Most patients with Peters anomaly have glaucoma. No FDA-approved glaucoma medications are available for children.)
Vitreoretinal surgeon - Lensectomy/vitrectomy
Cornea specialist - Keratoplasty
Low-vision specialist - Management of poor vision, provision of optical aids

Follow-up

Further Outpatient Care

An ophthalmologist should provide regular follow-up care for patients with graft rejection and glaucoma.
A pediatrician should monitor patients for other congenital anomalies.
Patients should receive visual rehabilitation as needed.
A pediatric contact lens specialist should fit patients with aphakic contact lenses.

Inpatient & Outpatient Medications

Medications may be indicated for glaucoma and postgraft treatment.

Complications

Complications include amblyopia and decreased vision or blindness from glaucoma.
Complications of corneal transplantation and cataract surgery are numerous.

Prognosis

The visual prognosis is guarded. The earlier the keratoplasty is performed, the better the chances of preventing deprivation amblyopia. The visual acuity in patients after keratoplasty was 20/80 or worse in most series; some series reported a visual acuity of 20/40 in patients. Also, in most series, the chances that patients maintain a clear graft were 30-50% at 10 years. Patients with glaucoma and cataract had a worse prognosis.
The prognosis for life depends on other systemic anomalies.

Patient Education

Children with Peters anomaly require special educational needs depending on the visual outcome. A low-vision specialist should evaluate these children. Patients may need loupes and binoculars depending on the visual potential.

Miscellaneous

Medicolegal Pitfalls

Failure to recognize Peters anomaly from other conditions that mimic it
Failure to refer to other specialists to rule out systemic anomalies
Failure to provide regular follow-up care for those children with graft rejection or glaucoma
Failure to offer visual rehabilitation

Special Concerns

Cases of Peters anomaly have been reported to occur with fetal alcohol syndrome. Drinking during pregnancy should be discouraged.

References

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Keywords

Peter's anomaly, Peters anomaly, keratolenticular dysgenesis, congenital central corneal leukoma, dysgenesis mesodermalis of the cornea, anterior segment dysgenesis

Contributor Information and Disclosures

Author

Guruswami Arunagiri, MD, FRCS, Department of Ophthalmology, Permanente Medical Group, Sacramento, CA
Guruswami Arunagiri, MD, FRCS is a member of the following medical societies: American Academy of Ophthalmology
Disclosure: Nothing to disclose.

Medical Editor

Brian A Phillpotts, MD, Former Vitreo-Retinal Service Director, Former Program Director, Clinical Assistant Professor, Department of Ophthalmology, Howard University College of Medicine
Brian A Phillpotts, MD is a member of the following medical societies: American Academy of Ophthalmology, American Diabetes Association, American Medical Association, and National Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Christopher J Rapuano, MD, Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Co-Chairman of the Cornea Service, Co-Chairman of Refractive Surgery Department, Wills Eye Institute
Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Cornea Society, Eye Bank Association of America, International Society of Refractive Surgery, and Pan-American Association of Ophthalmology
Disclosure: Allergan Honoraria Speaking and teaching; Allergan Consulting fee Consulting; Alcon Honoraria Speaking and teaching; Inspire Honoraria Speaking and teaching; RPS Ownership interest Other; Vistakon Honoraria Speaking and teaching

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the assistance of Ryan I Huffman, MD, with the literature review and referencing for this article.

Further Reading