Craniosynostosis in a patient with 2q37.3 deletion 5q34 duplication: association of extra copy of MSX2 with craniosynostosis.

We report on a 1-year-old boy with craniosynostosis, microcephaly, developmental delay and dysmorphic features. Chromosomal studies of the proband showed 46,XY,add(2)(q37)dn and those of the parents were normal. The rearranged material in the patient was further defined using array comparative genomic hybridization (array CGH), which revealed loss of 2Mb distal to 2q37.3 and duplication of 15Mb from 5q34 --> qter. Fluorescence in situ hybridization (FISH) studies using subtelomeric 2q and 5q probes showed the 2q deletion and 5q duplication resulting from a rearrangement of the segment from 5q onto the long arm of chromosome 2. FISH studies of the parents did not show any rearrangement. Recently it has been proposed that an extra copy of MSX2 that maps to 5q35.2 causes premature synostosis of the sutures via the MSX2-mediated pathway of calvarial osteogenic differentiation. Our case further supports the role of MSX2 duplication in the etiology of craniosynostosis.