Douglas et al. (2007) identified 4 individuals with an overgrowth syndrome characterized by increased postnatal height and weight, macrocephaly, variable learning disability, and dysmorphic facial features. Although none had clinical features of neurofibromatosis I (162200), the facial features ... Douglas et al. (2007) identified 4 individuals with an overgrowth syndrome characterized by increased postnatal height and weight, macrocephaly, variable learning disability, and dysmorphic facial features. Although none had clinical features of neurofibromatosis I (162200), the facial features were similar to the NF1 microdeletion syndrome (see 613675), including broad forehead, downslanting palpebral fissures, broad nasal tip, long philtrum, and thin upper lip. Variable features in 1 or 2 patients included deafness, optic nerve hypoplasia, advanced bone age, ataxia, autistic features, and pulmonary stenosis.
Douglas et al. (2007) identified heterozygous mutations in the RNF135 gene (611358.0001-611358.0004) in 4 of 245 unrelated individuals with an overgrowth syndrome. One additional individual had a microdeletion including RNF135 and 4 other genes, but not NF1 (613113). ... Douglas et al. (2007) identified heterozygous mutations in the RNF135 gene (611358.0001-611358.0004) in 4 of 245 unrelated individuals with an overgrowth syndrome. One additional individual had a microdeletion including RNF135 and 4 other genes, but not NF1 (613113). Douglas et al. (2007) concluded that haploinsufficiency of RNF135 contributes to the overgrowth and facial dysmorphism that is often present in individuals with NF1 microdeletions, as well as learning disabilities and other congenital anomalies.