Knobloch syndrome

Title

Other Names:

Myopia retinal detachment encephalocele

Categories:

Congenital and Genetic Diseases; Eye diseases

Summary Summary

Knobloch syndrome is characterized by severe vision problems and skull defects.^[1] The most common features include extreme nearsightedness (high myopia), recurrent retinal detachment, and occipital encephalocele.^[1]^[2] There are three types of Knobloch syndrome, which can be distinguished by the underlying genetic cause. Knobloch syndrome type I is caused by mutations in the COL18A1 gene. The genes associated with Knobloch syndrome type 2 and type 3 have not been identified; however, Knobloch syndrome type 3 has been linked to a specific region on chromosome 17, known as 17q11.2.^[2]^[3] Knobloch syndrome follows an autosomal recessive pattern of inheritance.^[1]^[2]^[3] Treatment is aimed at addressing the symptoms present in each individual and may include surgery to repair retinal detachments and occiptal encephaloceles.^[3]

Last updated: 10/18/2016

Symptoms Symptoms

The three main features of Knobloch syndrome are severe nearsightedness (high myopia), recurrent retinal detachment, and occipital encephalocele.^[1]^[2]^[3] The severe myopia develops early on in life, and is usually diagnosed within the first year. Affected individuals may have additional eye abnormalities, such as congenital cataracts, iris abnormalities, and lens subluxation (when the lens of the eye drifts off-center). An encephalocele is a sac-like protrusion of the brain through an opening in the base of the skull (the occipital bone). A variety of other signs and symptoms have been described in affected individuals. Intelligence is not affected by Knobloch syndrome.^[3]

Last updated: 10/18/2016

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Calvarial skull defect	Very frequent (present in 80%-99% of cases)
Macular degeneration	Very frequent (present in 80%-99% of cases)
Myopia	Very frequent (present in 80%-99% of cases)
Occipital encephalocele	Very frequent (present in 80%-99% of cases)
Retinal detachment	Very frequent (present in 80%-99% of cases)
Abnormality of the vitreous humor	Frequent (present in 30%-79% of cases)
Hydrocephalus	Frequent (present in 30%-79% of cases)
Nystagmus	Frequent (present in 30%-79% of cases)
Progressive visual loss	Frequent (present in 30%-79% of cases)
Vitreoretinal degeneration	Frequent (present in 30%-79% of cases)
Abnormality of the hair	Occasional (present in 5%-29% of cases)
Bifid ureter	Occasional (present in 5%-29% of cases)
Cataract	Occasional (present in 5%-29% of cases)
Dextrocardia	Occasional (present in 5%-29% of cases)
Ectopia lentis	Occasional (present in 5%-29% of cases)
Epicanthus	Occasional (present in 5%-29% of cases)
Joint hyperflexibility	Occasional (present in 5%-29% of cases)
Lymphangioma	Occasional (present in 5%-29% of cases)
Mental deterioration	Occasional (present in 5%-29% of cases)
Midface retrusion	Occasional (present in 5%-29% of cases)
Patent ductus arteriosus	Occasional (present in 5%-29% of cases)
Pyloric stenosis	Occasional (present in 5%-29% of cases)
Seizures	Occasional (present in 5%-29% of cases)
Strabismus	Occasional (present in 5%-29% of cases)
Vesicoureteral reflux	Occasional (present in 5%-29% of cases)
Ataxia	-
Autosomal recessive inheritance	-
Band keratopathy	-
Cerebellar atrophy	-
Cerebral atrophy	-
Congenital cataract	-
Macular hypoplasia	-
Phenotypic variability	-
Phthisis bulbi	-
Polymicrogyria	-
Severe Myopia	-
Ventriculomegaly	-
Visual loss	-

Last updated: 9/1/2017

Cause Cause

Some cases of Knobloch syndrome are caused by mutations in the COL18A1 gene.^[1]^[2]^[3] This gene provides instructions for making a protein that is used to assemble type XVIII collagen. Collagens are a family of proteins that strengthen and support connective tissues, such as skin, bone, tendons, and ligaments, throughout the body.^[1] The condition has also been linked to a specific region on chromosome 17, known as 17q11.2. However, researchers have not determined which gene in this region is associated with Knobloch syndrome.^[2]^[3]

Last updated: 10/18/2016

Inheritance Inheritance

Knobloch syndrome has an autosomal recessive pattern of inheritance, which means that both copies of the gene in each cell have mutations.^[1]^[2]^[3] The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they do not show signs and symptoms of the condition.^[1] When 2 carriers of an autosomal recessive condition have children, each cild has a:

25% chance to be affected
50% chance to be an unaffected carrier like each parent
25% chance to be unaffected and not a carrier

Last updated: 10/18/2016

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Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Knobloch syndrome. This website is maintained by the National Library of Medicine.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Knobloch syndrome. Click on the link to view a sample search on this topic.

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