Knobloch Syndrome 1

Clinical Characteristics
Ocular Features: 

The ocular findings include high myopia, vitreoretinal degeneration, dislocated lenses, cataracts, and retinal detachment.  Some patients have early onset (2-4 years old) night blindness and progress to total blindness before 20 years of age.  Nystagmus, strabismus, small optic discs, glaucoma, and cataracts have been reported.  Poor vision and progressive loss of acuity are common.  The vitreous appears to be condensed into sheets and there may be distortion of the vitreoretinal interface with irregular white dots and lines.  Pigmentary changes are common in the retina which some have described as consistent with choroidal sclerosis and chorioretinal atrophy.  Atrophic changes are often seen in the macula.

Systemic Features: 

The degree of skull and brain defects is variable.  Some patients have only occipital scalp defects while others have occipital encephaloceles.  The scalp defect may contain heterotopic neuronal tissue suggesting neuronal migratory defects.  Brain imaging has revealed a variety of defects and some patients have cognitive deficits and personality changes.  Cerebellar atrophy with ataxia is found in some patients.


This is an autosomal recessive disorder secondary to homozygous mutations in the COL18A1 gene (21q22.3).  Mutated COL18A1 leads to defects in type XVIII collagen which is a component of basement membranes throughout the body, especially in the eye.

In spite of some clinical similarities, this disorder is genetically distinct from Knobloch 2 syndrome (608454).  A third type, KNO3, has been proposed since the Knobloch clinical features were found in a 4-generation consanguineous Pakistani family but the phenotype mapped to 17q11.2.

Treatment Options: 

Treatment is largely supportive.  Attempts at repair of retinal detachments often fail and phthisis bulbi is not uncommon.

Article Title: 


White RJ, Wang Y, Tang P, Montezuma SR. Knobloch syndrome associated with Polymicrogyria and early onset of retinal detachment: two case reports. BMC Ophthalmol. 2017 Nov 25;17(1):214. doi: 10.1186/s12886-017-0615-z.

PubMedID: 29178892

Mahajan VB, Olney AH, Garrett P, Chary A, Dragan E, Lerner G, Murray J, Bassuk AG. Collagen XVIII mutation in Knobloch syndrome with acute lymphoblastic leukemia. Am J Med Genet A. 2010 Nov;152A(11):2875-9.

PubMedID: 20799329

Kliemann SE, Waetge RT, Suzuki OT, Passos-Bueno MR, Rosemberg S. Evidence of neuronal migration disorders in Knobloch syndrome: clinical and molecular analysis of two novel families. Am J Med Genet A. 2003 May 15;119A(1):15-9.

PubMedID: 12707952