Holoprosencephaly (HPE) is the most common forebrain defect in humans. It results from incomplete midline cleavage of the prosencephalon and can be caused by environmental and genetic factors. HPE is usually described as a continuum of brain malformations from the most severe alobar HPE to the middle interhemispheric fusion variant or syntelencephaly. A microform of HPE is limited to craniofacial features such as congenital nasal pyriform aperture stenosis and single central maxillary incisor, without brain malformation. Among the heterogeneous causes of HPE, point mutations and deletions in the SHH gene at 7q36 have been identified as well as extremely rare chromosomal rearrangements in the long-range enhancers of this gene. Here, we report a boy with an HPE microform associated with a Currarino syndrome. Array CGH detected a de novo 2.7-Mb deletion in the 7q36.3 region including the MNX1 gene, usually responsible for the Currarino triad but excluding SHH, which is just outside the deletion. This new case provides further evidence of the importance of the SHH long-range enhancers in the HPE spectrum.
Keywords: Currarino syndrome; Holoprosencephaly; Long-range enhancers; Microdeletion 7q36; Sonic hedgehog.