Peters Plus Syndrome is a rare, inherited disorder that disrupts the normal development of several parts of the body. It is most known for causing abnormalities in the structures at the front of the eye. The condition also involves short stature, distinctive facial characteristics, and potential developmental delays. As a congenital disorder, its signs are present from birth and can vary significantly in severity from one person to another.
The Genetic Cause of Peters Plus Syndrome
Peters Plus Syndrome arises from mutations in a specific gene known as B3GLCT. This gene holds the instructions for producing an enzyme called beta 3-glucosyltransferase (B3Glc-T), which modifies proteins by adding sugar molecules to them (a process called glycosylation). This modification is important for proteins to carry out their functions throughout the body.
Most mutations in the B3GLCT gene result in the creation of an abnormally short and nonfunctional version of the B3Glc-T enzyme. The loss of this enzyme’s function impairs the glycosylation process, which likely disrupts how numerous proteins work, contributing to the diverse features of the syndrome. Peters Plus Syndrome is inherited in an autosomal recessive pattern. This means that for an individual to have the condition, they must inherit one mutated copy of the B3GLCT gene from each parent. The parents are considered carriers but do not show symptoms of the syndrome themselves.
Key Physical and Developmental Characteristics
Ocular Abnormalities
The most consistent feature of the syndrome relates to the eyes, specifically a condition called Peters anomaly. This anomaly is a form of anterior segment dysgenesis, meaning the structures at the front of the eye did not form correctly. It results in the central part of the cornea—the clear outer layer of the eye—becoming cloudy or opaque, which can blur vision. Additionally, the iris, the colored part of the eye, may have adhesions that connect it to the cornea.
This improper development of the eye’s anterior chamber also leads to a higher risk of other ocular issues. Glaucoma, a condition of increased pressure inside the eye, is common and can damage vision over time. Many individuals with Peters Plus Syndrome may also develop cataracts, which is the clouding of the eye’s lens. These eye abnormalities are present in both eyes.
Skeletal and Growth Features
A universal characteristic of Peters Plus Syndrome is short stature, which is often apparent even before birth. Adult height for females with the condition ranges from 128 to 151 centimeters (4 feet, 2 inches to 4 feet, 11 inches), while for males it ranges from 141 to 155 centimeters (4 feet, 7 inches to 5 feet, 1 inch). The short stature is often disproportionate, with a shortening of the upper limbs (rhizomelia).
In addition to height, individuals often have small hands and feet with short fingers and toes (brachydactyly).
Distinctive Facial Features
Individuals with Peters Plus Syndrome often share a set of recognizable facial characteristics. These include a prominent forehead and a long philtrum (the vertical groove between the base of the nose and the upper lip). A particularly notable feature is an exaggerated “Cupid’s bow” shape of the upper lip.
Furthermore, about half of the individuals with this syndrome are born with a cleft lip, with or without a cleft palate. The ears may be small or malformed, and some individuals may have a broad or webbed neck.
Developmental Aspects
Developmental progress can be variable for those with Peters Plus Syndrome. Developmental delay is observed in approximately 80% of children, affecting milestones like walking and speech. The spectrum of intellectual ability is wide, ranging from mild to severe intellectual disability. However, some individuals with the syndrome have normal cognitive functioning. The severity of the physical features does not necessarily predict the level of intellectual development.
The Diagnostic Process
The diagnosis of Peters Plus Syndrome is a multistep process that combines observations of physical traits with definitive genetic analysis. The first indications may appear before birth, as prenatal ultrasounds can sometimes detect abnormalities such as short long bones or an increased nuchal translucency. After birth, diagnosis begins with a comprehensive clinical evaluation.
A physician will perform a thorough physical examination, looking for the characteristic features of the syndrome, such as eye abnormalities, short stature with disproportionate limbs, and distinct facial traits. A specialized and detailed eye examination by a pediatric ophthalmologist is also performed. This exam assesses the specific structural issues in the anterior segment of the eye, confirming the presence of corneal clouding, iridocorneal adhesions, and checking for related conditions like glaucoma and cataracts.
Imaging studies of the eye, such as an ultrasound, might be used to get a clearer picture of the internal structures. The definitive diagnosis is achieved through molecular genetic testing. This involves a laboratory analysis, usually of a blood sample or a swab from inside the cheek, to identify the presence of mutations in both copies of the B3GLCT gene.
Management and Supportive Care
There is no cure for Peters Plus Syndrome, so management focuses on addressing the specific symptoms and providing comprehensive supportive care. This requires a multidisciplinary team of healthcare professionals, including ophthalmologists, pediatricians, geneticists, and various therapists, to manage the individual’s health needs.
Ocular Care
Vision preservation is a primary goal of management. For infants with severe, bilateral corneal clouding, a corneal transplant (penetrating keratoplasty) may be considered within the first few months of life to prevent amblyopia, a condition of poor eye-brain coordination. In milder cases, a surgeon might perform a procedure to simply separate the adhesions between the iris and cornea. The management of glaucoma is also important and may involve medications to lower eye pressure or surgical interventions.
Surgical Repair
For the approximately half of individuals born with a cleft lip and/or palate, surgical repair is a standard part of care. These surgeries are typically performed in infancy and childhood to correct the structural abnormalities, which can improve feeding, speech development, and facial appearance.
Therapeutic Support
Early intervention with various therapies helps manage the developmental aspects of the syndrome. Physical therapy can help with motor skill challenges related to short limbs and other skeletal issues. Occupational therapy assists in developing skills for daily living. Speech therapy is important for individuals with developmental delays or a cleft palate affecting communication.
Ongoing Monitoring
Continuous monitoring is required throughout an individual’s life. Regular check-ups with a pediatric ophthalmologist are needed to monitor for the progression of glaucoma and to manage amblyopia. Developmental assessments should be conducted regularly to ensure that the child is receiving appropriate educational and developmental support.