Peters-plus syndrome

Overview

Peters-plus syndrome is a rare genetic disorder characterized by a combination of eye abnormalities, short stature, and distinctive facial and skeletal features. The most defining characteristic of the syndrome is Peters anomaly, a congenital eye defect involving malformation of the anterior segment of the eye, which often leads to corneal clouding and visual impairment. Additional systemic features may include cleft lip and/or palate, developmental delay, and abnormalities in brain and genitourinary structure. Peters-plus syndrome is inherited in an autosomal recessive pattern and typically presents in infancy. The condition is distinct from isolated Peters anomaly, which occurs without the systemic features seen in Peters-plus syndrome.

Causes

Peters-plus syndrome is caused by mutations in the B3GLCT gene (formerly known as B3GALTL), located on chromosome 13. This gene encodes a beta-1,3-glucosyltransferase enzyme that is important in the glycosylation process—a modification of proteins that is critical for normal development and cellular function.

The syndrome follows an autosomal recessive inheritance pattern, meaning that a child must inherit two defective copies of the B3GLCT gene—one from each parent—to develop the condition. Parents of an affected child are typically asymptomatic carriers of the mutation.

Symptoms

The clinical features of Peters-plus syndrome are variable but typically involve a combination of ocular, facial, skeletal, and developmental abnormalities. Key symptoms include:

Ocular Features:

• Peters anomaly: A developmental defect of the anterior eye segment causing central corneal opacity, adhesions between the iris and cornea, and sometimes lens abnormalities

• Corneal clouding: May lead to significant visual impairment or blindness

• Microphthalmia: Abnormally small eyes (in some cases)

Growth and Skeletal Abnormalities:

• Short stature: Noticeably below average height

• Rhizomelic shortening: Shortening of the upper limbs (humerus or femur)

• Joint contractures: In some patients, limited joint mobility

Craniofacial Features:

• Round face with full cheeks

• Prominent forehead

• Small nose with a broad nasal bridge

• Thin upper lip

• Cleft lip and/or palate

Other Systemic Features:

• Developmental delay: Ranging from mild to moderate intellectual disability

• Hearing loss: May occur due to middle ear abnormalities

• Brain abnormalities: Including hydrocephalus or corpus callosum agenesis in some cases

• Genitourinary malformations: Such as hypospadias, kidney anomalies, or cryptorchidism

Not all individuals with Peters-plus syndrome will exhibit every symptom. Severity can vary widely even among affected siblings.

Diagnosis

Diagnosis of Peters-plus syndrome is based on clinical features, eye examination findings, imaging studies, and genetic testing to confirm the presence of mutations in the B3GLCT gene.

Diagnostic Process:

• Ophthalmologic evaluation: Slit-lamp examination to detect Peters anomaly

• Clinical examination: Assessment of growth patterns, facial morphology, and developmental milestones

• Radiologic imaging: X-rays or MRI to evaluate skeletal abnormalities and brain structure

• Genetic testing: Molecular analysis of the B3GLCT gene to confirm diagnosis

• Prenatal testing: May be possible if both parents are known carriers

Diagnosis must differentiate Peters-plus syndrome from isolated Peters anomaly and other syndromes that cause corneal opacity and growth delay.

Treatment

There is no cure for Peters-plus syndrome. Treatment is supportive and aimed at managing individual symptoms and improving the patient’s quality of life. A multidisciplinary team including ophthalmologists, geneticists, developmental pediatricians, and surgeons is typically involved in care.

Management Strategies:

Ocular Treatment:

• Corneal transplantation: May be attempted to restore vision in cases of significant corneal clouding

• Glaucoma management: If secondary glaucoma is present

• Vision support services: Including low-vision aids and specialized education

Growth and Orthopedic Care:

• Regular monitoring of growth and skeletal development

• Physical and occupational therapy for joint stiffness or contractures

Craniofacial and ENT Management:

• Surgical correction: Of cleft lip/palate if present

• Hearing aids or surgery: For conductive hearing loss

Developmental and Educational Support:

• Early intervention programs for speech, motor, and cognitive development

• Special education plans tailored to individual learning needs

Monitoring for Other Anomalies:

• Regular renal and cardiac assessments if abnormalities are suspected

Prognosis

The prognosis for Peters-plus syndrome varies depending on the severity of the ocular and systemic involvement. Some individuals may have relatively mild developmental delays and good functional outcomes, while others may experience significant disability due to visual impairment, cognitive delay, or other congenital anomalies. Early diagnosis, prompt treatment of complications, and access to supportive therapies can improve quality of life and developmental outcomes.

Life expectancy may be reduced in severe cases, particularly if life-threatening anomalies are present. However, with appropriate multidisciplinary care, many individuals with Peters-plus syndrome can achieve meaningful developmental progress and live fulfilling lives. Genetic counseling is recommended for affected families to discuss recurrence risks and reproductive options.