Microdeletion 1q42.12q42.2 in a boy with hypogenesis of the corpus callosum

Agenesis of the corpus callosum (ACC) is common amongst brain malformations. The underlying genetic defects of ACC are variable, reflecting the complexity of callosal development. ACC has been described in association with different microdeletions, often located at the chromosomal region 1q44. In two cases the microdeletion was located at 1q42 more than 10 Mb proximal of 1q44. We report on a 3-year-old boy from Iraq who is the first child of non-consanguineous parents. Family history and pregnancy were unremarkable. The postnatal period was characterized by sleep and feeding problems. At the age of 3 years a febrile seizure occurred. Speech development was delayed, behaviour was hyperactive and aggressive. He had mild facial dysmorphism with inverse epicanthic folds and two café-au-lait spots. Cranial MRI showed hypogenesis of the corpus callosum. Metabolic and ophthalmologic examinations did not detect any abnormality. SNP oligonucleotide array testing revealed a 3.6 Mb duplication in chromosomal region 1q25.1 and a 4.2 Mb deletion in chromosomal region 1q42.12q42.2.. The duplication encompassed 30 RefSeq genes, none of them being an OMIM annotated disease gene. The deleted region harbors 40 RefSeq genes, five of them listed to be associated with diseases (PSEN2, CABCA1, GJC2, ACTA1, AGT). Our observation is in keeping with two previous reports on ACC patients with deletions of 1q42. This region is more than 10 Mb apart from 1q44 where deletions are known to cause ACC. Our finding supports the notion of an independent ACC-associated region at 1q42. Some of the genes located in this region, e.g. WNT3A (OMIM *603341) and RHOU (*606366), have been discussed as candidates of ACC and neural tube defects. Behavioural abnormalities and speech delay in our patient may be explained as consequences of ACC. However a phenotypic effect of the duplication at 1q25.1 cannot be excluded. This report underpins the role of 1q42 microdeletion as a potential cause of agenesis/hypogenesis of the corpus callosum.