Peters-plus syndrome or Krause–Kivlin syndrome is a
hereditary
Heredity, also called inheritance or biological inheritance, is the passing on of traits from parents to their offspring; either through asexual reproduction or sexual reproduction, the offspring cells or organisms acquire the genetic inform ...
syndrome
A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek σύνδρομον, meaning "concurrence". When a syndrome is paired ...
defined by
Peters' anomaly,
dwarfism
Dwarfism is a condition wherein an organism is exceptionally small, and mostly occurs in the animal kingdom. In humans, it is sometimes defined as an adult height of less than , regardless of sex; the average adult height among people with dw ...
and
intellectual disability
Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation,Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signifi ...
.
[
]
Signs and symptoms
Features of this syndrome include Peters' anomaly, corneal opacity
The human cornea is a transparent membrane which allows light to pass through it. The word corneal opacification literally means loss of normal transparency of cornea. The term corneal opacity is used particularly for the loss of transparency of c ...
, central defect of Descemet's membrane
Descemet's membrane ( or the Descemet membrane) is the basement membrane that lies between the corneal proper substance, also called stroma, and the endothelial layer of the cornea. It is composed of different kinds of collagen (Type IV and VIII) ...
, and shallow anterior chamber with synechiae between the iris and cornea.
Craniofacial abnormalities commonly seen in patients with PPS include hypertelorism
Hypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits (eyes), or orbital hypertelorism. In this condition the distance between the inner eye corners as ...
, ear malformations, micrognathia
Micrognathism is a condition where the jaw is undersized. It is also sometimes called mandibular hypoplasia. It is common in infants, but is usually self-corrected during growth, due to the jaws' increasing in size. It may be a cause of abnorm ...
, round face and broad neck, and cleft lip
A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The te ...
and palate
The palate () is the roof of the mouth in humans and other mammals. It separates the oral cavity from the nasal cavity.
A similar structure is found in crocodilians, but in most other tetrapods, the oral and nasal cavities are not truly sepa ...
.[
Infants are commonly born small for gestational age and have delayed growth. It is associated with short limb ]dwarfism
Dwarfism is a condition wherein an organism is exceptionally small, and mostly occurs in the animal kingdom. In humans, it is sometimes defined as an adult height of less than , regardless of sex; the average adult height among people with dw ...
and mild to severe intellectual disability
Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation,Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signifi ...
and autism spectrum disorder
The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental disorder, neurodevelopmental condition (or conditions) ...
.
Cause
The pattern of inheritance of Peters-plus is autosomal recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
, where both parents are heterozygous they can produce a child with the syndrome. The B3GALTL (now called B3GLCT) gene codes for the enzyme beta 3-glucosyltransferase (B3Glc-T).
The beta 3-glucosyltransferase enzyme is responsible for glycosylation
Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not al ...
, the attachment of sugars to proteins, which through this modification allows for performance of a wider variety of functions. The mutations of the B3GLCT gene in affected individuals results in loss-of-function of the beta 3-glucosyltransferase enzyme. The result of this disruption in glycosylation is a change to the secondary structure
Protein secondary structure is the three dimensional conformational isomerism, form of ''local segments'' of proteins. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...
of the mRNA. These mutations of the B3GLCT gene lead to the production of an abnormally short, nonfunctional version of the beta 3-glucosyltransferase Glucosyltransferases are a type of glycosyltransferase that enable the transfer of glucose.
Examples include:
* glycogen synthase
* glycogen phosphorylase
Glycogen phosphorylase is one of the phosphorylase enzymes (). Glycogen phosphorylase c ...
(B3Glc-T) enzyme, which disrupts glycosylation.
The phenotypic effects of the B3GLCT mutations result in a triad of well known phenotypes; Peters anomaly (also classified as anterior segment defects, a defect in the anterior cornea), short stature, brachydactyly
Brachydactyly (Greek βραχύς = "short" plus δάκτυλος = "finger"), is a medical term which literally means "short finger". The shortness is relative to the length of other long bones and other parts of the body. Brachydactyly is an in ...
, in addition to several other less frequently observed phenotypes. A study of 55 patients with Peters-plus-related phenotypes, but lacking the most common combination (Peters anomaly, short stature, and brachydactyly), revealed none of those cases displayed mutation in the B3GLCT gene. Thus PPS-like signs and symptoms, when they occur independently of each other, provide strong evidence that the B3GLCT gene mutation is in fact responsible for actual cases Peters-plus syndrome.
History
Krause–van Schooneveld–Kivlin syndrome is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
(NIH).[
]
It was characterized in 1984 by van Schooneveld.
See also
* Peters anomaly
Anterior segment mesenchymal dysgenesis, or simply anterior segment dysgenesis (ASD), is a failure of the normal development of the tissues of the anterior segment of the eye. It leads to anomalies in the structure of the mature anterior segment, ...
References
External links
GeneReviews/NCBI/NIH/UW entry on Peters Plus Syndrome
OMIM entries on Peters Plus syndrome
* {{eMedicine, article, 1200372, Peters Anomaly on eMedicine
eMedicine is an online clinical medical knowledge base founded in 1996 by doctors Scott Plantz and Jonathan Adler, and computer engineer Jeffrey Berezin. The eMedicine website consists of approximately 6,800 medical topic review articles, each of ...
Rare syndromes