¹Department of Paediatrics and Child Health, Dunedin School of Medicine, Otago University, Dunedin, New Zealand

Correspondence: Professor SP Robertson, Clinical Genetics Laboratory, Department of Paediatrics and Child Health, Dunedin School of Medicine, University of Otago, PO Box 913, Dunedin 9001, New Zealand. Tel: +64 3 479 7469; Fax: +64 3 479 7469; E-mail: stephen.robertson@stonebow.otago.ac.nz

Received 19 December 2005; Revised 18 April 2006; Accepted 21 April 2006; Published online 23 August 2006.

Abstract

The term otopalatodigital syndrome spectrum disorders is an umbrella category that includes four phenotypically related conditions, otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia and Melnick–Needles syndrome. The phenotype of these conditions in the male ranges from a severe perinatally lethal multiple malformation syndrome to a mild skeletal dysplasia. Most, but not all, instances of these conditions are associated by mutations in the X-linked gene encoding the cytoskeletal protein filamin A. Mutations in this gene are clustered, exhibit a strong genotype–phenotype correlation and are presumed to exert their effect by a gain-of-function mechanism.