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Disease Profile

Knobloch syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

Q15.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Myopia retinal detachment encephalocele; Knobloch-Layer syndrome; Retinal detachment-occipital encephalocele syndrome

Categories

Congenital and Genetic Diseases; Eye diseases

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]

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]

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.

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

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]

Organizations

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

      Organizations Providing General Support

        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

          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.

            References

            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; https://www.omim.org/entry/267750.
            3. Dulac O. Knobloch syndrome. Orphanet. September 2008; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=1571.

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