Knobloch syndrome (KS) is defined by vitreoretinal and macular degeneration, and occipital encephalocele. The exact prevalence is unknown but less than 30 cases have been reported in the literature so far. KS is characterized by early-onset severe myopia (usually becoming apparent in the first year of life), vitreoretinal degeneration with retinal detachment, macular abnormalities, and midline encephalocele (mainly in the occipital region). Predisposition to hydrocephalus is frequent. Ocular abnormalities vary and may include congenital cataract, iris abnormalities, and lens subluxation. Numerous extraocular abnormalities have been described: 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. Epilepsy has been reported in isolated cases. Intelligence is normal. KS is inherited as an autosomal recessive trait. The syndrome is clinically and genetically heterogeneous with three forms, KNO1, KNO2 and KNO3, being defined. KNO1 is caused by inactivating mutations in the collagen XVIII/endostatin gene (COL18A1) mapped to 21q22.3. The KNO2 form was defined when linkage to the KNO1 locus was excluded in a family reported from New Zealand. Recently, a novel type of KS (KNO3) was mapped to chromosome 17q11.2. Diagnosis is based on ocular abnormalities and occipital encephalocele (detected by computed tomography and magnetic resonance imaging). The differential diagnosis should include the following syndromes: Stickler, Wagner, Marshall, Meckel and HARD±E syndrome (see these terms). Management of the ocular manifestations requires referral to an ophthalmologist specialist in retinopathies. Treatment modalities include retinal reattachment surgery, prophylactic treatment of the vitreoretinal pathology and photodynamic therapy. Encephalocele should be treated by surgical methods, aiming to restore normal anatomy with repair of the defective dura, bone and skin. The eye findings in KS are severe and progressive, and regularly lead to bilateral blindness at a young age.
Last update: September 2008