Peters plus syndrome is characterized by anterior chamber eye anomalies, disproportionate short stature, variable developmental delay/intellectual disability, characteristic facial features, and cleft lip/palate. The most common anterior chamber defect is Peters' anomaly, consisting of a central corneal opacification, thinning of the posterior cornea, and iridocorneal adhesions, and ranging from mild to severe. Cataracts and glaucoma are common. Growth deficiency with rhizomelic limb shortening is invariably present. Developmental delay is observed in about 80% of children; although some adults have normal cognitive function, intellectual disability can range from mild to severe. Cleft lip is present in 45% and cleft palate in 33%.
Diagnosis is based on clinical findings and molecular genetic testing of B3GALTL, the only gene in which mutations are known to cause Peters plus syndrome. Most affected individuals tested to date are homozygous for a hot spot splice mutation in intron 8 (c.660+1G>A).
Peters plus syndrome is inherited in an autosomal recessive manner. The parents of an affected child are obligate heterozygotes and thus carry one mutant allele. Heterozygotes (carriers) are asymptomatic. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. There is an increased chance for miscarriages and second- and third-trimester fetal loss of homozygously affected fetuses. Carrier testing for at-risk family members and prenatal diagnosis for pregnancies at increased risk are possible if the disease-causing mutations in the family are known.