National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Knobloch syndrome


Other Names:
Myopia retinal detachment encephalocele; Knobloch-Layer syndrome; Retinal detachment-occipital encephalocele syndrome
Categories:
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
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

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 39 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Calvarial skull defect
Cranial defect
Skull defect
[ more ] 		0001362
Macular degeneration 0000608
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness
[ more ] 		0000545
Occipital encephalocele
Brain tissue sticks out through back of skull
0002085
Retinal detachment
Detached retina
0000541
30%-79% of people have these symptoms
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Progressive visual loss
Progressive loss of vision
Progressive vision loss
Progressive visual impairment
Slowly progressive visual loss
Vision loss, progressive
Visual loss, progressive
[ more ] 		0000529
Vitreoretinopathy 0007773
5%-29% of people have these symptoms
Abnormal hair morphology
Abnormality of the hair
Hair abnormality
[ more ] 		0001595
Bifid ureter 0030037
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root
[ more ] 		0005280
Dextrocardia
Heart tip and four chambers point towards right side of body
0001651
Ectopia lentis 0001083
Epicanthus
Eye folds
Prominent eye folds
[ more ] 		0000286
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Lymphangioma 0100764
Mental deterioration
Cognitive decline
Cognitive decline, progressive
Intellectual deterioration
Progressive cognitive decline
[ more ] 		0001268
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface
[ more ] 		0011800
Patent ductus arteriosus 0001643
Pyloric stenosis 0002021
Seizure 0001250
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
Vesicoureteral reflux 0000076
Percent of people who have these symptoms is not available through HPO
Alopecia
Hair loss
0001596
Ataxia 0001251
Autosomal recessive inheritance 0000007
Band keratopathy 0000585
Cerebellar atrophy
Degeneration of cerebellum
0001272
Cerebral atrophy
Degeneration of cerebrum
0002059
Developmental cataract
Clouding of the lens of the eye at birth
0000519
High myopia
Severe near sightedness
Severely close sighted
Severely near sighted
[ more ] 		0011003
Macular hypoplasia 0001104
Peripapillary atrophy 0500087
Phthisis bulbi 0000667
Polymicrogyria
More grooves in brain
0002126
Ventriculomegaly 0002119
Visual loss
Loss of vision
Vision loss
[ more ] 		0000572
Showing of 39 |
Last updated: 7/1/2020
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
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

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The differential diagnosis should include the following syndromes: Stickler, Wagner, Marshall, Meckel and HARD±E syndrome (see these terms).
Visit the Orphanet disease page for more information.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Social Networking Websites

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

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.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • How did Knobloch syndrome get its name? Is severe myopia one of the main symptoms? See answer


  1. Knobloch syndrome. Genetics Home Reference (GHR). June 2011; https://ghr.nlm.nih.gov/condition/knobloch-syndrome.
  2. Knobloch syndrome, type I. Online Mendelian Inheritance in Man (OMIM). September 19, 2016; http://www.omim.org/entry/267750.
  3. Dulac O. Knobloch syndrome. Orphanet. September 2008; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=1571.