Peters plus syndrome is a rare genetic disorder characterized by a combination of ocular (eye) and systemic features. It is also known as Krause-Kivlin syndrome. Peters plus syndrome is named after the ocular anomalies associated with the condition, and it is characterized by a broad spectrum of features that can vary in severity among affected individuals. The estimated prevalence is less than 1 case per 1.000.000 population.
Peters plus syndrome genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
Critical features of Peters plus syndrome include:
Ocular Anomalies
- Anterior segment dysgenesis is a malformation of the front part of the eye, which may include abnormalities of the cornea, iris, and lens.
- Peters anomaly is a specific type of anterior segment dysgenesis characterized by central corneal opacity and defects in the posterior layers of the cornea.
- Cataracts: Clouding of the lens of the eye.
- Axial myopia: Nearsightedness due to elongation of the eyeball.
Systemic Features
- Short stature: Individuals with Peters plus syndrome may have a shorter than average height.
- Brachydactyly: Shortening of the fingers or toes.
- Developmental delay: Delays in achieving developmental milestones.
- Intellectual disability: Intellectual challenges, ranging from mild to moderate, may be present.
- Characteristic facial features: Facial features may include a flat nasal bridge, a small mouth, and a prominent upper lip.
Other Possible Features
- Hearing loss: Sensorineural hearing loss may be present.
- Cardiac anomalies: Some individuals with Peters plus syndrome may have congenital heart defects.
- Genitourinary anomalies: Abnormalities of the genital or urinary tract may occur.
Peters plus syndrome is caused by mutations in the B3GALTL gene, which provides instructions for making an enzyme involved in producing complex sugars that are crucial for normal development.
Diagnosis is typically based on clinical features, and genetic testing can confirm the presence of mutations in the B3GALTL gene.
Management of Peters plus syndrome involves a multidisciplinary approach, addressing each individual's specific needs. Treatment may include corrective surgeries for ocular anomalies, early intervention and developmental support for intellectual and developmental challenges, and management of associated health issues.
Genetic counseling is essential for families affected by Peters plus syndrome to understand the inheritance pattern, assess the risk of having affected children, and discuss available reproductive options. Due to the complexity of the condition, a team of healthcare professionals, including ophthalmologists, geneticists, and developmental specialists, may be involved in caring for individuals with Peters Plus syndrome.
More Information
The origin of the disease lies in the presence of mutations in the B3GLCT gene encoding for the enzyme beta-1,3-glycosyltransferase involved in the O-glycosylation of proteins, a cellular process essential for the formation of glycosylated proteins in the Golgi apparatus. The enzyme beta-1,3-glucosyltransferase glycosylates proteins of the ADAMTS superfamily that play critical roles in the extracellular matrix and are involved in cell signaling and organ and tissue formation during development.
The c.660+1G>A mutation (also known as c.1020+1G>A) is the most common mutation in patients with Peters plus syndrome, accounting for 69% of all pathogenic alleles and found in 0.01% of Europeans (non-Finnish) according to genomAD. The c.1020+1G>A variant can occur in both homozygous and compound heterozygous patients. This variant affects the canonical cleavage and splicing site of intron 8 and leads to the deletion of exon 8, producing a degraded nonsense-mediated mRNA.
The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).
