Corpus Callosum, Agenesis Of, With Mental Retardation, Ocular Coloboma, And Micrognathia

A number sign (#) is used with this entry because agenesis of the corpus callosum with mental retardation, ocular coloboma, and micrognathia is caused by mutation in the IGBP1 gene (300139).

Clinical Features

Graham et al. (2003) described 2 brothers with a seemingly unique pattern of malformations that included coloboma of the iris and optic nerve, high forehead, severe retrognathia, mental retardation, and agenesis of the corpus callosum. Both boys had low-set cupped ears with sensorineural hearing loss, pectus excavatum, scoliosis, and short stature. One brother had choanal atresia and cardiac defects in the form of ventricular septal defect (VSD) and patent ductus arteriosus (PDA) which resolved spontaneously.

Molecular Genetics

Because agenesis of the corpus callosum and the distinctive facial features were reminiscent of FG syndrome (305450), Graham et al. (2003) analyzed DNA for markers linked to the FGS1 locus at Xq13-q21. The brothers were concordant for markers spanning this presumed FG region, and in both Graham et al. (2003) identified adjacent alterations in the region just 5-prime of the AUG translation initiation codon of the IGBP1 gene (which they called alpha-4): -57delT and 55T-A (300139.0001). The mother was shown to be a carrier of both changes, which were located in the 5-prime UTR of the gene. The altered sequence was not present in the mother's half brother or in her maternal grandmother. It also was not found in the DNA from 410 control chromosomes or in the DNA from patients with mental retardation syndromes that map to this region, and was not found in patients with Opitz G/BBB syndrome (300000) in whom no mutation in MID1 (300552) had been detected. The last testing was done because of the demonstrated interaction between alpha-4 and MID1.