Peters plus syndrome is an inherited condition that is characterized by eye abnormalities, short stature, an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate), distinctive facial features, and intellectual disability.

The eye problems in Peters plus syndrome occur in an area at the front part of the eye known as the anterior segment. The anterior segment consists of structures including the lens, the colored part of the eye (iris), and the clear covering of the eye (cornea). An eye problem called Peters anomaly is the most common anterior segment abnormality seen in Peters plus syndrome. Peters anomaly involves abnormal development of the anterior segment, which results in a cornea that is cloudy (opaque) and causes blurred vision. Peters anomaly may also be associated with clouding of the lenses of the eyes (cataracts) or other lens abnormalities. Peters anomaly is usually bilateral, which means that it affects both eyes. The severity of corneal clouding and other eye problems can vary between individuals with Peters plus syndrome, even among members of the same family. Many people with Peters plus syndrome experience vision loss that worsens over time.

All people with Peters plus syndrome have short stature, which is evident before birth. The height of adult males with this condition ranges from 141 centimeters to 155 centimeters (4 feet, 7 inches to 5 feet, 1 inch), and the height of adult females ranges from 128 centimeters to 151 centimeters (4 feet, 2 inches to 4 feet, 11 inches). Individuals with Peters plus syndrome also have shortened upper limbs (rhizomelia) and shortened fingers and toes (brachydactyly).

The characteristic facial features of Peters plus syndrome include a prominent forehead; small, malformed ears; narrow eyes; a long area between the nose and mouth (philtrum); and a pronounced double curve of the upper lip (Cupid's bow). The neck may also be broad and webbed. A cleft lip with or without a cleft palate is present in about half of the people with this condition.

Developmental milestones, such as walking and speech, are delayed in most children with Peters plus syndrome. Most affected individuals also have intellectual disability that can range from mild to severe, although some have normal intelligence. The severity of physical features does not predict the level of intellectual disability.

Less common signs and symptoms of Peters plus syndrome include heart defects, structural brain abnormalities, hearing loss, and kidney or genital abnormalities.

Peters plus syndrome is a rare disorder; its incidence is unknown. Fewer than 80 people with this condition have been reported worldwide.

Mutations in the B3GLCT gene cause Peters plus syndrome. The B3GLCT gene provides instructions for making an enzyme called beta 3-glucosyltransferase (B3Glc-T), which is involved in the complex process of adding sugar molecules to proteins (glycosylation). Glycosylation modifies proteins so they can perform a wider variety of functions. Most mutations in the B3GLCT gene lead to the production of an abnormally short, nonfunctional version of the B3Glc-T enzyme, which disrupts glycosylation. It is unclear how the loss of functional B3Glc-T enzyme leads to the signs and symptoms of Peters plus syndrome, but impaired glycosylation likely disrupts the function of many proteins, which may contribute to the variety of features.

Genetic Testing Information

• Genetic Testing Registry: Peters plus syndrome

Genetic and Rare Diseases Information Center

• Peters plus syndrome

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• PETERS-PLUS SYNDROME; PTRPLS

Scientific Articles on PubMed

• PubMed

• Hess D, Keusch JJ, Oberstein SA, Hennekam RC, Hofsteenge J. Peters Plus syndrome is a new congenital disorder of glycosylation and involves defective Omicron-glycosylation of thrombospondin type 1 repeats. J Biol Chem. 2008 Mar 21;283(12):7354-60. doi: 10.1074/jbc.M710251200. Epub 2008 Jan 16. Citation on PubMed
• Lesnik Oberstein SA, Kriek M, White SJ, Kalf ME, Szuhai K, den Dunnen JT, Breuning MH, Hennekam RC. Peters Plus syndrome is caused by mutations in B3GALTL, a putative glycosyltransferase. Am J Hum Genet. 2006 Sep;79(3):562-6. doi: 10.1086/507567. Epub 2006 Jul 19. Erratum In: Am J Hum Genet. 2006 Nov;79(5):985. Citation on PubMed or Free article on PubMed Central
• Lesnik Oberstein SAJ, Ruivenkamp CAL, Hennekam RC. Peters Plus Syndrome. 2007 Oct 8 [updated 2017 Aug 24]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1464/ Citation on PubMed
• Maillette de Buy Wenniger-Prick LJ, Hennekam RC. The Peters' plus syndrome: a review. Ann Genet. 2002 Apr-Jun;45(2):97-103. doi: 10.1016/s0003-3995(02)01120-6. Citation on PubMed
• Reis LM, Tyler RC, Abdul-Rahman O, Trapane P, Wallerstein R, Broome D, Hoffman J, Khan A, Paradiso C, Ron N, Bergner A, Semina EV. Mutation analysis of B3GALTL in Peters Plus syndrome. Am J Med Genet A. 2008 Oct 15;146A(20):2603-10. doi: 10.1002/ajmg.a.32498. Citation on PubMed or Free article on PubMed Central
• Schoner K, Kohlhase J, Muller AM, Schramm T, Plassmann M, Schmitz R, Neesen J, Wieacker P, Rehder H. Hydrocephalus, agenesis of the corpus callosum, and cleft lip/palate represent frequent associations in fetuses with Peters' plus syndrome and B3GALTL mutations. Fetal PPS phenotypes, expanded by Dandy Walker cyst and encephalocele. Prenat Diagn. 2013 Jan;33(1):75-80. doi: 10.1002/pd.4012. Epub 2012 Nov 13. Citation on PubMed