Climbing the Branches of a Family Tree: Diagnosis of Fragile X Syndrome

• Type of Material: Article
• Authors: Jeannie Visootsak, Emory University; Heather Hipp, Emory University; Heather Clark, Emory University; Elizabeth Berry-Kravis, Rush University; Tovi Anderson, Emory University; Dawn Laney, Emory University
• Language: English
• Date: 2014-06-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jpeds.2014.01.051
• Title of Journal or Parent Work: Journal of Pediatrics
• ISSN: 0022-3476
• Volume: 164
• Issue: 6
• Start Page: 1292
• End Page: 1295
• Grant/Funding Information: E.B-K. has received funding from Asuragen, Inc to develop testing standards for diagnosis of FXS.; J.V. and E.B-K. receive grant support from Novartis and Roche to conduct clinical trials and consult on use of mGluR5 blockers in individuals with FXS.; Supported by National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development (1K23HD058043-01A1 to J.V.) and Fragile X Association of Georgia (to T.A.).
• Keywords: TREMOR/ATAXIA SYNDROME FXTAS; Life Sciences & Biomedicine; Science & Technology; Pediatrics; MALES; FMR1; DISORDERS; MINOCYCLINE
• Research Categories: Biology, Genetics

Abstract

Objective To determine the average number of family members diagnosed with a Fragile X Mental Retardation-1 (FMR1) mutation after a proband receives the initial diagnosis of fragile X syndrome (FXS). Study design We reviewed pedigrees of families who had been evaluated at the Fragile X Syndrome Center at Emory University in Atlanta, Georgia. Through these pedigrees, we determined the number of additional family members diagnosed as FMR1 premutation carriers or with full mutation FXS after the initial diagnosis in each proband. Results The fragile X pedigree review identified 176 probands, including 108 males (61%) and 68 females (39%). A total of 785 family members were diagnosed with expanded fragile X alleles, including 278 males (35%) and 507 females (65%). These family members included 227 individuals with full mutation FXS (219 males and 8 females) and 558 premutation carriers (59 males and 499 females). After the initial diagnosis of a proband with FXS, on average at least 5 additional family members were diagnosed with an FMR1 mutation. Conclusion Our findings confirm that obtaining a detailed family history after diagnosis of a proband with FXS is likely to identify multiple family members with FMR1 mutations. It is important that the pediatrician or other health care provider making a diagnosis of FXS recognize the value of a detailed family history for timely diagnosis and treatment of additional individuals who may be FMR1 premutation carriers or have full mutation FXS.