ß 2008 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 146A:940–943 (2008) Correspondence Clarification of Previously Reported Costello Syndrome Patients Angela E. Lin, 1 * Katherine A. Rauen, 2,3 Karen W. Gripp, 4 and John C. Carey 5 1 Genetics Unit, MassGeneral Hospital for Children, Boston, Massachusetts 2 Comprehensive Cancer Center, Division of Medical Genetics, University of California, San Francisco, California 3 Division of Medical Genetics, Department of Pediatrics, University of California, San Francisco, California 4 Division of Medical Genetics, A. I. Du Pont Hospital for Children, Wilmington, Delaware 5 Division of Medical Genetics, Department of Pediatrics, Primary Children’s Medical Center, Salt Lake City, Utah Received 4 June 2007; Accepted 12 October 2007 How to cite this article: Lin AE, Rauen KA, Gripp KW, Carey JC. 2008. Clarification of previously reported Costello syndrome patients. Am J Med Genet Part A 146A:940 – 943. To the Editor: Shortly after Aoki et al. [2005] reported that mutations in the HRAS gene caused Costello syndrome, Gripp et al. [2006] and Estep et al. [2006] published patient cohorts (40 and 36 clinically diagnosed patients, respectively) describing the frequency of HRAS muta- tions, and both discussed genotype-phenotype cor- relations. The ‘‘Editor’s Note’’ [Carey, 2006] that accompanied the article by Estep et al. [2006] acknowl- edged that both groups of investigators had collected samples from patients and obtained consents from family members at the 2001, 2003, and 2005 Costello Syndrome meetings. Since the patients’ identities could not be revealed for review, the Editor-in-Chief (J.C.) relied on phenotypic clinical details from both authors to determine that there were ‘‘20 patients that participated in both investigations,’’ and that the two studies had ‘‘investigated at least 56 patients.’’ Gripp et al. [2006, Table I] presented the clinical details of 40 individual patients (33 HRASþ,7 HRAS), whereas Estep et al. [2006 Table IV] summarized the data of 36 patients (33 HRASþ,3 HRAS) patients in aggregate form. To enhance the clinical information available to other researchers, we report an annotated list (Table I) of these patients. Each study has been carried out under its own institutional IRB protocol with inherent privacy protection, and thus, patient analysis continues to be based upon review of clinical features. Costello syndrome has several distinctive clinical features, such as hypertrophic cardiomyopathy, cardiac arrhythmia (especially chaotic/multifocal atrial tachycardia), papil- lomata and neoplasia (especially rhabdomyosarcoma), which enabled one of the authors (A.E.L.) to perform a comparison of the patients’ clinical features to determine the ‘‘phenotypic identity’’ of subjects in each study. Importantly, the aggregate patient data of Estep et al. [2006] is expanded to include individual patients [Table I]. We report now that 17 patients were described by both authors, 16 patients reported only by Gripp et al. [2006] and 16 patients reported only by Estep et al. [2006], for a total of 49 patients (in contrast to the hypothetical maximum of 56 in the original articles). By maintaining an ongoing review of the literature, we also determined that patient 11 in Gripp et al. [2006] and included in Estep et al. [2006] was subsequently reported as patient 1 in Kerr et al. [2006] based on the patient’s sex and age, and the highly distinctive phenotype (pulmonic stenosis, severe hypertrophic cardiomyopathy, supraventricular tachycardia, growth hormone use, rhabdomyosarcoma), as well as the citations included by the authors [Dearlove and Harper, 1997; Kerr et al., 1998; Lin et al., 2002]. Similarly, patient 8 in Kerr et al. [2006] had been described in the reviews of Lin et al. [2002], Gripp et al. [2002] and Hinek et al. [2005]. At the time patient recruitment was initiated in 2001, the relatively new Costello Syndrome support group did not have either a formal Medical/Profes- sional Advisory Board or an ad hoc Research Advisory Group to prospectively define research guidelines, that is whether the organization would interact with researchers in a traditional or innovative model for collecting data, vetting projects and executing projects. The Genetic Alliance has since recommended that *Correspondence to: Dr. Angela E. Lin, M.D., Genetics Unit, MassChildren Hospital for Children, 175 Cambridge St., Suite 501A, Boston, MA 02114. E-mail: lin.angela@mgh.harvard.edu DOI 10.1002/ajmg.a.32164