Another TWIST on Baller-Gerold syndrome

Baller-Gerold syndrome is characterized by craniosynostosis and preaxial up per limb malformations. Wide heterogeneity exists with regard to the presen ce of additional anomalies. Most of the 31 reported cases involve other mal formations, including cardiac, Central Nervous System (CNS), and urogenital anomalies. Baller-Gerold syndrome is thought to have autosomal recessive i nheritance. However, Gripp et al. [1999; Am. J. Med. Genet. 82:170-176] rec ently provided the first evidence for autosomal dominant inheritance with v ariable expressivity and severity. A nonsense mutation was found in TWIST, a gene associated with Saethre-Chotzen syndrome (SCS). Here we report on a male Caucasian patient of nonconsanguineous parents, with synostosis of the coronal, metopic, and sagittal sutures, and bilateral radial ray hypoplasi a. The patient's small, round ears with prominent crus helices, and cervica l anomalies are common features of SCS. The father had very mild features o f SCS. We identify direct paternal transmission of a novel missense TWIST m utation in the highly conserved Helix II domain of this bHLH-family gene. T his report lends further support to the recent findings by Gripp et al. [19 99]. Future TWIST mutational analysis on patients with craniosynostosis and radial ray involvement will shed light on whether Baller-Gerold syndrome s hould be a distinct entity or some cases should be reclassified as a hetero geneous form of SCS. (C) 2001 Wiley-Liss, Inc.