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.
Knobloch syndrome is caused by mutation in the collagen XVIII/endostatin (COL18A1) gene, located on 21q22.3 chromosome. Most COL18A1 gene mutations lead to defects in type XVIII collagen which is a component of basement membranes throughout the body, especially in the eye. At least two other unidentified genes may cause Knobloch syndrome types II and III. Although they are caused by mutations in different genes, the three types of the condition have similar signs and symptoms.
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.
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