What are the other Names for this Condition? (Also known as/Synonyms)

• Myopia Retinal Detachment Encephalocele

What is Knobloch Syndrome? (Definition/Background Information)

• Knobloch Syndrome is characterized by severe vision problems and skull defects. The most common features include extreme nearsightedness (high myopia), recurrent retinal detachment, and occipital encephalocele
• There are three types of Knobloch Syndrome, which can be distinguished by the underlying genetic cause:
  • Knobloch Syndrome type 1 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
• Knobloch Syndrome follows an autosomal recessive pattern of inheritance
• Treatment is aimed at addressing the symptoms present in each individual and may include surgery to repair retinal detachments and occiptal encephaloceles

(Source: Knobloch Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Knobloch Syndrome? (Age and Sex Distribution)

• Knobloch Syndrome is a rare congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Knobloch Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Knobloch Syndrome can be inherited
• Currently, no other risk factors have been clearly identified for the syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Knobloch Syndrome? (Etiology)

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
• Knobloch Syndrome follows an autosomal recessive pattern of inheritance

Some cases of Knobloch Syndrome are caused by mutations in the COL18A1 gene.

• 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
• 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
• Knobloch Syndrome has an autosomal recessive pattern of inheritance, which means that both copies of the gene in each cell have mutations

(Source: Knobloch Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Knobloch Syndrome?

The signs and symptoms of Knobloch Syndrome may include:

• Ataxia
• Band keratopathy
• Cerebellar atrophy
• Cerebral atrophy
• Congenital cataract
• Macular hypoplasia
• Phthisis bulbi
• Polymicrogyria
• Severe myopia
• Ventriculomegaly
• Visual loss

The three main features of Knobloch Syndrome are severe nearsightedness (high myopia), recurrent retinal detachment, and occipital encephalocele.

• 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

Very frequently present symptoms in 80-99% of the cases:

• Calvarial skull defect
• Macular degeneration
• Myopia
• Occipital encephalocele
• Retinal detachment

Frequently present symptoms in 30-79% of the cases:

• Abnormality of the vitreous humor
• Hydrocephalus
• Nystagmus
• Progressive visual loss
• Vitreoretinal degeneration

Occasionally present symptoms in 5-29% of the cases:

• Abnormality of the hair
• Bifid ureter
• Cataract
• Dextrocardia
• Ectopia lentis
• Epicanthus
• Joint hyperflexibility
• Lymphangioma
• Mental deterioration
• Midface retrusion
• Patent ductus arteriosus
• Pyloric stenosis
• Seizures
• Strabismus
• Vesicoureteral reflux

(Source: Knobloch Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Knobloch Syndrome Diagnosed?

Knobloch Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Knobloch Syndrome?

The complications of Knobloch Syndrome may include:

• Congenital heart defects
• Intellectual impairment
• Vision loss

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Knobloch Syndrome Treated?

• The treatment of Knobloch Syndrome is aimed at addressing the symptoms present in each individual and may include surgery to repair retinal detachments and occiptal encephaloceles

(Source: Knobloch Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Knobloch Syndrome be Prevented?

Currently, Knobloch Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Knobloch Syndrome? (Outcomes/Resolutions)

• The prognosis of Knobloch Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Knobloch Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/