Peters Plus Syndrome is a rare congenital disorder classified as a syndromic developmental defect, meaning it involves a specific pattern of abnormalities across multiple tissues and organs. The condition is exceptionally uncommon, affecting less than one in a million people globally. As a disorder present at birth, it affects development, leading to a broad spectrum of features that vary widely in severity among affected individuals. This condition is also sometimes referred to by the alternative names Krause-Kivlin syndrome or Krause-van Schooneveld-Kivlin syndrome.
The Underlying Genetic Cause
Peters Plus Syndrome is an inherited condition that follows an autosomal recessive pattern, meaning an individual must inherit a mutated copy of the responsible gene from both parents to develop the syndrome. The gene implicated in this disorder is the B3GLCT gene, which was previously known as B3GALTL. This gene provides the instructions for creating an enzyme called Beta-1,3-glucosyltransferase (B3Glc-T).
The B3Glc-T enzyme plays a specific role in a process called glycosylation, which involves adding sugar molecules to proteins to modify their function. This modification is particularly important for proteins that contain Thrombospondin Type 1 Repeats (TSRs), which are domains found in many proteins involved in cell signaling and development.
Mutations in the B3GLCT gene typically result in the production of an abnormally short and nonfunctional version of the B3Glc-T enzyme. This loss of function disrupts the necessary glycosylation of TSR-containing proteins, impairing their structure and stability. The resulting molecular dysfunction during embryonic development leads to the wide array of physical symptoms observed in Peters Plus Syndrome.
Characteristic Physical Manifestations
The most commonly recognized feature of this syndrome involves the eyes, specifically a condition known as Peters anomaly. This defect affects the anterior segment of the eye, manifesting as a clouding of the central cornea, often with adhesions between the iris and the cornea.
The ocular involvement is typically bilateral, affecting both eyes, and can be associated with other severe eye conditions such as cataracts and glaucoma. Glaucoma, characterized by increased pressure within the eye, can further damage the optic nerve and worsen vision loss over time. The severity of the corneal clouding and other eye issues can vary significantly.
The syndrome also includes distinct features related to growth and the skeleton. All affected individuals experience short stature, which is often detectable before birth. Adult males with the condition often reach heights between 141 and 155 centimeters, while adult females typically range from 128 to 151 centimeters in height.
Skeletal abnormalities include shortened limbs, particularly in the upper arm and thigh bone regions, a condition known as rhizomelia. Affected individuals commonly have brachydactyly, characterized by unusually short fingers and toes. These skeletal features, combined with the short stature, contribute to a characteristic body habitus.
Craniofacial features provide further defining characteristics of the syndrome. Individuals may have a distinctive facial appearance that includes a prominent forehead, a long area between the nose and the upper lip called the philtrum, and a pronounced double curve of the upper lip known as a Cupid’s bow. Approximately half of the people with Peters Plus Syndrome are born with a cleft lip, which may or may not be accompanied by a cleft palate.
Developmental milestones, such as walking and speech, are often delayed in children with the condition. Most affected individuals have some degree of intellectual disability, which can range from mild to severe, though some individuals exhibit normal cognitive function. Other less common features include congenital heart defects, structural brain abnormalities, and abnormalities of the kidneys and genitourinary system.
Confirming the Diagnosis
The initial diagnosis of Peters Plus Syndrome is typically based on the clinical observation of the characteristic physical features. A clinician will look for the specific combination of the Peters anomaly eye defect, short stature, and other distinctive facial or skeletal findings. The presence of these multiple anomalies strongly suggests the clinical diagnosis.
Confirmation of the clinical suspicion relies on molecular genetic testing. This process involves sequencing the B3GLCT gene to identify mutations in both copies of the gene. Identifying these specific genetic changes provides definitive evidence that the syndrome is present.
Specialized tests are also conducted early in life, particularly a comprehensive eye examination by a pediatric ophthalmologist. This assessment evaluates the extent of corneal clouding, the presence of iridocorneal adhesions, and the risk for glaucoma. Imaging studies, such as ultrasound or MRI, may also be used to examine internal structures, including the eyes and brain, to document the full scope of the condition. When a specific gene mutation is identified in a family, prenatal diagnosis can become an option for future pregnancies.
Long-Term Medical Management
Since there is no curative treatment for the underlying genetic cause of Peters Plus Syndrome, management is supportive and focuses on addressing the specific symptoms to improve function and quality of life. A multidisciplinary team approach is necessary, involving pediatricians, geneticists, ophthalmologists, and other specialists. Early intervention services are also a component of the care plan.
The management of ocular defects is particularly complex and requires specialized intervention. Severe bilateral corneal clouding often necessitates surgical procedures like penetrating keratoplasty, which is a corneal transplant. This surgery is often performed in infancy to prevent severe vision loss and amblyopia. Less severe cases may benefit from simpler surgical separation of iridocorneal adhesions.
Glaucoma requires careful and ongoing medical or surgical intervention, though it can be challenging to manage in this population. Certain medications, such as corticosteroids, must be used with caution or avoided entirely, as they can increase intraocular pressure and complicate glaucoma management. Regular monitoring by a pediatric ophthalmologist is necessary to track the progression of eye issues, particularly glaucoma and amblyopia.
For growth and skeletal issues, orthopedic specialists and physical therapists are often involved to address limb shortening and brachydactyly. In some cases, endocrine monitoring and the consideration of growth hormone replacement therapy may be part of the treatment plan. The developmental delays seen in many affected children are addressed through specialized educational programs and physical, occupational, and speech therapy services tailored to individual needs.