Raymond et al. (2007) described 4 families with X-linked mental retardation, 3 of which had marfanoid habitus as an additional feature. None of the affected individuals met the Ghent criteria for Marfan syndrome (154700). Pectus carinatum, pes planus, ... Raymond et al. (2007) described 4 families with X-linked mental retardation, 3 of which had marfanoid habitus as an additional feature. None of the affected individuals met the Ghent criteria for Marfan syndrome (154700). Pectus carinatum, pes planus, arachnodactyly, strabismus, prominent ears, and fifth finger camptodactyly were reported. One patient had major behavioral problems, and a diagnosis of schizophrenia (181500) had been made. Another patient had pyloric stenosis. In the family without marfanoid habitus, clinical diagnosis of FG syndrome was considered (see 305450) in one affected member because of the presence of hypotonia, a cowlick, and a high forehead.
In 4 of 250 families with X-linked mental retardation, Raymond et al. (2007) identified mutations in highly conserved residues of the ZDHHC9 gene: 1 frameshift mutation (300646.0001), 1 splice site mutation (300646.0002), and 2 missense mutations (300646.0003), (300646.0004). ... In 4 of 250 families with X-linked mental retardation, Raymond et al. (2007) identified mutations in highly conserved residues of the ZDHHC9 gene: 1 frameshift mutation (300646.0001), 1 splice site mutation (300646.0002), and 2 missense mutations (300646.0003), (300646.0004). In 3 of the families, the mental retardation phenotype was associated with a marfanoid habitus. Raymond et al. (2007) stated that ZDHHC9 was the first X-linked mental retardation (XLMR) gene to be reported that encodes a posttranslational modification enzyme. ZDHHC9 is a palmitoyltransferase that catalyzes the posttranslational modification of NRAS (164790) and HRAS (190020). The finding of mutations in ZDHHC9 suggested that alterations in the concentrations and cellular distribution of target proteins are sufficient to cause disease. Tarpey et al. (2009) sequenced the coding exons of the X chromosome in 208 families with X-linked mental retardation. One frameshift mutation and one splice site mutation in the ZDHHC9 gene were identified in 2 independent families. The mutations segregated with the phenotype and were not found in any unaffected individuals. In addition to mental retardation, the phenotype included marfanoid habitus.