Symposium introduction

At the 23rd David W. Smith Workshop on Malformations and Morphogenesis held in August 2002, one of the sessions focused on Kabuki syndrome. This syndrome, originally described in Japanese patients, is recognized internationally with over 300 cases in literature. The diagnosis is based on the ‘‘facial gestalt’’ in combination with congenital anomalies such as a cleft palate and/or heart defect, mild to moderate developmental delay, hand anomalies, and a variety of other features. The abstracts of all articles and posters on Kabuki syndrome, presented at the Workshop, have been reported in the Proceedings of the Greenwood Genetic Center, 2003, volume 22. A few articles have been selected for publication in this special section of the American Journal of Medical Genetics. In this issue, Armstrong et al. [2004] present an international series of patients, and review the clinical data in relation to the literature. They also show that the mean paternal age is higher than expected, thus underlining the hypothesis that a de novo autosomal dominant mutation might cause Kabuki syndrome. Schrander-Stumpel et al. [2004] present clinical data in a Dutch group and focus on guidelines for preventive management. Vaux et al. [2004] present the neonatal phenotype; they point out that nuchal thickening during early pregnancy may be a first clue. Mervis et al. [2004] report on cognitive and adaptive behavior in Kabuki syndrome: there appears to be a wide range of intellectual functioning as well as a wide range of adaptive functioning. Defloor et al. [2004] investigate exploration language in a series of patients with Kabuki syndrome. Finally, Ming et al. [2004] focus on immune dysfunction in the syndrome. Before making the diagnosis, a cytogenetic anomaly must be ruled out. Features resembling those in Kabuki syndrome have been reported in a number of cytogenetic conditions: mosaic X chromosome abnormality, paracentric inversion of 4p, pseudodicentric chromosome 13, partial 6q monosomy/ partial 12q trisomy, and some cases of 22q11 deletion. [For references, see Schrander-Stumpel et al., 2004.] Recently an 8p22-8p23.1 duplication was reported in six individuals with Kabuki syndrome [Milunsky and Huang, 2003]. A study of 26 Japanese and 2 Thai patients with Kabuki syndrome failed to reveal such a duplication [Miyake et al., 2004]. Further exploration of this finding will be one of the challenges for 2004. No candidate genes have been reported so far.