Newly recognised craniosynostosis syndrome that does not map to known disease loci

We describe a consanguineous family of Pakistani origin with five sibs, thr ee of whom were affected by craniosynostosis of variable presentation. In a ddition, they had other congenital abnormalities principally affecting neur ological, ocular, and limb development. We provide linkage evidence using i ntragenic and flanking microsatellite markers suggesting that the disease i n this family was not caused by a mutation in one of the known craniosynost osis loci (FGFR1, FGFR2, FGFR3, MSX2, TWIST). Given the clinical novelty an d parental consanguinity, we hypothesise that the affected individuals were autozygous for a recessively inherited mutation, at a novel locus, predisp osing to craniosynostosis. (C) 2000 Wiley-Liss,Inc.