Knobloch syndrome is a rare

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

presenting severe

eyesight Visual perception is the ability to interpret the surrounding environment through photopic vision (daytime vision), color vision, scotopic vision (night vision), and mesopic vision (twilight vision), using light in the visible spectrum reflect ...

problems and often a defect in the

skull The skull is a bone protective cavity for the brain. The skull is composed of four types of bone i.e., cranial bones, facial bones, ear ossicles and hyoid bone. However two parts are more prominent: the cranium and the mandible. In humans, th ...

. It was named after the ophthalmologist William Hunter Knobloch (1926 - 2005), who first described the syndrome in 1971. A usual occurrence is a degeneration of the

vitreous humour The vitreous body (''vitreous'' meaning "glass-like"; , ) is the clear gel that fills the space between the lens and the retina of the eyeball (the vitreous chamber) in humans and other vertebrates. It is often referred to as the vitreous humor ...

and the

retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which the ...

, two components of the eye. This breakdown often results in the separation of the retina (the light-sensitive tissue at the back of the eye) from the eye, called

retinal detachment Retinal detachment is a disorder of the eye in which the retina peels away from its underlying layer of support tissue. Initial detachment may be localized, but without rapid treatment the entire retina may detach, leading to vision loss and blin ...

, which can be recurrent. Extreme

myopia Near-sightedness, also known as myopia and short-sightedness, is an eye disease where light focuses in front of, instead of on, the retina. As a result, distant objects appear blurry while close objects appear normal. Other symptoms may includ ...

(near-sightedness) is a common feature. The limited evidence available from

electroretinography Electroretinography measures the electrical responses of various cell types in the retina, including the photoreceptors ( rods and cones), inner retinal cells ( bipolar and amacrine cells), and the ganglion cells. Electrodes are placed on th ...

suggests that a

cone A cone is a three-dimensional geometric shape that tapers smoothly from a flat base (frequently, though not necessarily, circular) to a point called the apex or vertex. A cone is formed by a set of line segments, half-lines, or lines con ...

- rod pattern of dysfunction is also a feature. Knobloch syndrome is caused by

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...

s in an

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 an ...

inherited

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. These mutations have been found in the

COL18A1 Collagen alpha-1(XVIII) chain is a protein that in humans is encoded by the ''COL18A1'' gene. This gene encodes the alpha chain of type XVIII collagen. This collagen is one of the multiplexins, extracellular matrix proteins that contain multipl ...

gene that instructs for the formation of a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that builds collagen XVIII. This type of collagen is found in the

basement membrane The basement membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tissues including mesothelium an ...

s of various body tissues. Its deficiency in the eye is thought to be responsible for affecting normal eye development. There are two types of Knobloch syndrome and the case has been made for a third. When caused by mutations in the COL18A1 gene it is called Knobloch syndrome type 1. The genes causing types II and III have yet to be identified. Knobloch syndrome is also characterised by

cataracts A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble ...

, dislocated lens with skull defects such as occipital encephalocele and occipital

aplasia Aplasia (; from Greek ''a'', "not", "no" + ''plasis'', "formation") is a birth defect where an organ or tissue is wholly or largely absent. It is caused by a defect in a developmental process. Aplastic anemia is the failure of the body to produc ...

. Encephalocele is a

neural tube In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural fold become elevated, ...

defect where the skull has not completely closed and sac-like protrusions of the brain can push through the skull; (it can also result from other causes). In Knobloch's syndrome this is usually seen in the occipital region, and aplasia is the underdevelopment of tissue again in this reference in the occipital area.

References

{{Congenital malformations and deformations of eye Congenital disorders of nervous system Syndromes affecting the eye Rare syndromes