Knobloch syndrome is an autosomal recessive condition characterized by high myopia, vitreoretinal degeneration, dislocated lenses, cataracts, and retinal detachment. Knobloch syndrome is a rare condition. However, the exact prevalence is unknown but less than 30 cases have been reported. Affected individuals may also have other abnormalities including: abnormal lymphatic vessels in the lung, patent ductus arteriosus, a single umbilical artery, pyloric stenosis, a flat nasal bridge, midface hypoplasia, bilateral epicanthic folds, cardiac dextroversion, generalized hyperextensibility of the joints, unusual palmar creases, and unilateral duplication of the renal collecting system. Encephaloceles may be associated with intellectual disability; however, most patients have normal intelligence. Diagnosis of KNO is based on ocular abnormalities and occipital encephalocele. Treatment is largely supportive, including retinal reattachment surgery, prophylactic treatment of the vitreoretinal pathology and photodynamic therapy.
Aldahmesh et al., (2011) described 13 patients from six consanguineous Saudi families with Knobloch syndrome. All affected patients except one (patient 6), had truncated homozygous mutations in COL18A1 gene. Patient 6, who did not have a mutation in the COL18A1 gene, was a 7-year-old girl presented with progressive retinal degeneration and serous retinal detachment. Using autozygosity mapping exome sequencing for patient 6, a novel homozygous missense mutation c.536C>T (p.Ser179Leu) was identified. Her both parents were heterozygous for this mutation, while her healthy siblings were homozygous for the wild-type allele. This mutation was not found in 386 Saudi control samples or in the Exome Variant Server.
Khan et al. (2012) described five consanguineous Saudi families with a total of eight children (aged between 4-15 years) affected with Knobloch syndrome. All children had smooth irides, high myopia, and distinctive vitreo-retinal degeneration consisting of diffuse very severe retinal pigment epithelium atrophic changes with mascular atrophic lesions with or without a punched out appearance, prominent choroidal vessel show, and white fibrillar vitreous condensations. In addition, six children had temporal ectopia lentis, found had posterior perinuclear lens opacity, two had developmental delay, one developed epilepsy, and one had heterotopic grey matter in the lateral ventricles. One of the families had mutation in the ADAMTS18 gene, while the other four families each had a homozygous mutation in the COL18A1 gene. Retinal detachment and/or phthisis was only present in the child with the ADAMTS18 mutation.