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Knobloch syndrome
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Knobloch syndrome

Knobloch syndrome is a rare genetic disorder characterized by severe vision problems, including extreme nearsightedness and vitreoretinal degeneration, and a skull defect known as an occipital encephalocele.

Overview

Knobloch syndrome is a rare condition characterized by severe vision problems and a skull defect.

Symptoms

A characteristic feature of Knobloch syndrome is extreme nearsightedness (high myopia). In addition, several other eye abnormalities are common in people with this condition. Most affected individuals have vitreoretinal degeneration, which is breakdown (degeneration) of two structures in the eye called the vitreous and the retina. The vitreous is the gelatin-like substance that fills the eye, and the retina is the light‑sensitive tissue at the back of the eye. Vitreoretinal degeneration often leads to separation of the retina from the back of the eye. Affected individuals may also have abnormalities in the central area of the retina, called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. Due to abnormalities in the vitreous, retina, and macula, people with Knobloch syndrome often develop blindness in one or both eyes.

Another characteristic feature of Knobloch syndrome is a skull defect called an occipital encephalocele, which is a sac‑like protrusion of the brain (encephalocele) through a defect in the bone at the base of the skull (occipital bone). Some affected individuals have been diagnosed with a different skull defect in the occipital region, and it is unclear whether the defect is always a true encephalocele. In other conditions, encephaloceles may be associated with intellectual disability; however, most people with Knobloch syndrome have normal intelligence.

Causes & Risk Factors

Mutations in the COL18A1 gene can cause Knobloch syndrome. The COL18A1 gene provides instructions for making a protein that forms collagen XVIII, which is found in the basement membranes of tissues throughout the body. Basement membranes are thin, sheet‑like structures that separate and support cells in these tissues. Collagen XVIII is found in the basement membranes of several parts of the eye, including the vitreous and retina, among other tissues. Little is known about the function of this protein, but it appears to be involved in normal development of the eye.

Several mutations in the COL18A1 gene have been identified in people with Knobloch syndrome. Most COL18A1 gene mutations lead to an abnormally short version of the genetic blueprint used to make the collagen XVIII protein. Although the process is unclear, the COL18A1 gene mutations result in the loss of collagen XVIII protein, which likely causes the signs and symptoms of Knobloch syndrome.

When the condition is caused by COL18A1 gene mutations, it is sometimes referred to as Knobloch syndrome type I. Research indicates that mutations in at least two other genes that have not been identified may cause Knobloch syndrome types II and III. Although they are caused by alterations in different genes, the three types of the condition have similar signs and symptoms.

Learn more about the gene associated with Knobloch syndrome

  • COL18A1

Inheritance

This condition is inherited in an autosomal recessive manner, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Other Names for This Condition

  • Retinal detachment and occipital encephalocele

Additional Information & Resources

Genetic Testing Information

  • Genetic Testing Registry: Knobloch syndrome 1

Genetic and Rare Diseases Information Center

  • Knobloch syndrome

Patient Support and Advocacy Resources

  • National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

  • KNOBLOCH SYNDROME 1; KNO1

Scientific Articles on PubMed

  • PubMed

References

  • Fukai N, Eklund L, Marneros AG, Oh SP, Keene DR, Tamarkin L, Niemela M, Ilves M, Li E, Pihlajaniemi T, Olsen BR. Lack of collagen XVIII/endostatin results in eye abnormalities. EMBO J. 2002 Apr 2;21(7):1535-44. doi:10.1093/emboj/21.7.1535. Citation on PubMed or Free article on PubMed Central
  • Passos-Bueno MR, Suzuki OT, Armelin-Correa LM, Sertie AL, Errera FI, Bagatini K, Kok F, Leite KR. Mutations in collagen 18A1 and their relevance to the human phenotype. An Acad Bras Cienc. 2006 Mar;78(1):123-31. doi:10.1590/s0001-37652006000100012. Epub 2006 Mar 8. Citation on PubMed
  • Seaver LH, Joffe L, Spark RP, Smith BL, Hoyme HE. Congenital scalp defects and vitreoretinal degeneration: redefining the Knobloch syndrome. Am J Med Genet. 1993 Apr 15;46(2):203-8. doi: 10.1002/ajmg.1320460221. Citation on PubMed
  • Seppinen L, Pihlajaniemi T. The multiple functions of collagen XVIII in development and disease. Matrix Biol. 2011 Mar;30(2):83-92. doi:10.1016/j.matbio.2010.11.001. Epub 2010 Dec 14. Citation on PubMed
  • Sertie AL, Sossi V, Camargo AA, Zatz M, Brahe C, Passos-Bueno MR. Collagen XVIII, containing an endogenous inhibitor of angiogenesis and tumor growth, plays a critical role in the maintenance of retinal structure and in neural tube closure (Knobloch syndrome). Hum Mol Genet. 2000 Aug 12;9(13):2051-8. doi:10.1093/hmg/9.13.2051. Citation on PubMed
  • Suzuki O, Kague E, Bagatini K, Tu H, Heljasvaara R, Carvalhaes L, Gava E, de Oliveira G, Godoi P, Oliva G, Kitten G, Pihlajaniemi T, Passos-Bueno MR. Novel pathogenic mutations and skin biopsy analysis in Knobloch syndrome. Mol Vis. 2009;15:801-9. Epub 2009 Apr 23. Citation on PubMed or Free article on PubMed Central

Frequently Asked Questions

Currently, there is no cure for Knobloch syndrome. Management focuses on treating the symptoms and complications, particularly those related to vision and the skull defect. The prognosis varies depending on the severity of the eye disease and the size of the encephalocele. While blindness is a common outcome due to progressive eye degeneration, many individuals lead fulfilling lives with appropriate support, assistive technologies, and medical management of any associated health issues.
Most individuals with Knobloch syndrome have normal intelligence and cognitive development. The primary challenges associated with the condition are related to vision and the structural skull defect. However, the severity of visual impairment can impact learning and daily activities, so early intervention with low-vision aids, educational support, and occupational therapy is crucial to help individuals maximize their potential and develop independent living skills.
Individuals with Knobloch syndrome require lifelong, specialized ophthalmologic care. Due to the high risk of retinal detachment and progressive vitreoretinal degeneration, regular monitoring by a retina specialist is essential. Treatment may involve surgical interventions to repair retinal detachments or manage other structural eye issues. Low-vision rehabilitation is also a critical component of care, providing tools and training to help individuals navigate their environment and perform daily tasks despite significant visual loss.
Diagnosis usually begins with a comprehensive eye examination that reveals extreme nearsightedness (high myopia) and signs of vitreoretinal degeneration, such as retinal detachment or macular abnormalities. A physical examination of the head may reveal an occipital encephalocele, a sac-like protrusion at the back of the skull. To confirm the diagnosis, genetic testing is performed to identify mutations in the COL18A1 gene. Imaging studies, such as MRI or CT scans of the head, are often used to assess the extent of the skull defect and any associated brain tissue involvement.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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