ABSTRACT
The X-linked form of Opitz G/BBB syndrome is a congenital midline malformation syndrome caused by MID1 loss-of-function mutations, including point mutations and small-sized duplications, insertions, and deletions. Three patients with an Opitz G/BBB syndrome phenotype and relatively large duplications of part of the MID1 gene have been described up to date. Here we report a 2-months-old boy with a very mild phenotype including craniofacial dysmorphism, swallowing difficulties, and a normal psychomotor development. Molecular karyotyping revealed a 57-kb duplication involving exon 2 of the MID1 gene. The in-frame tandem duplication was confirmed by MID1 transcript analysis. This alteration results likely in a mutant MID1 protein which contains 32 duplicated amino acids in the first part of the coiled-coil domain. The mild phenotype of the patient with the microduplication suggests that MID1 mutations can be found in patients with hypertelorism with or without other clinical signs and MID1 alterations might be missed in individuals not fulfilling the minimal criteria for diagnosis of X-linked Opitz G/BBB syndrome. This report further emphasizes the genotype-first approach in medical genetics in general and patients with unspecific clinical features in particular.
