Genetic investigation of patients with tall stature. Issue 2 (February 2020)

• Record Type: Journal Article
• Authors: Vasco de Albuquerque Albuquerque, Edoarda; Ferreira de Assis Funari, Mariana; Pereira de Souza Quedas, Elisângela; Sayuri Honjo Kawahira, Rachel; Soares Jallad, Raquel; Homma, Thaís Kataoka; Martin, Regina Matsunaga; Brito, Vinicius Nahime; Malaquias, Alexsandra Christianne; Lerario, Antonio Marcondes; Rosenberg, Carla; Victorino Krepischi, Ana Cristina; Ae Kim, Chong; Arnhold, Ivo Jorge Prado; Jorge, Alexander Augusto de Lima
• Is Part Of: European journal of endocrinology. Volume 182:Issue 2(2020)
• Page Start: 139
• Page End: 147
• Publication Date: 2020-02
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1530/EJE-19-0785
• Languages: English
• ISSNs: 0804-4643

Abstract

Abstract : Context: Patients with tall stature often remain undiagnosed after clinical investigation and few studies have genetically assessed this group, most of them without a systematic approach. Objective: To assess prospectively a group of individuals with tall stature, with and without syndromic features, and to establish a molecular diagnosis for their growth disorder. Design: Screening by karyotype ( n = 42), chromosome microarray analyses (CMA) ( n = 16), MS-MLPA ( n = 2) targeted panel ( n = 12) and whole-exome sequencing ( n = 31). Patients and methods: We selected 42 patients with tall stature after exclusion of pathologies in GH/IGF1 axis and divided them into syndromic ( n = 30) and non-syndromic ( n = 12) subgroups. Main outcome measures: Frequencies of pathogenic findings. Results: We identified two patients with chromosomal abnormalities including SHOX trisomy by karyotype, one 9q22.3 microdeletion syndrome by CMA, two cases of Beckwith–Wiedemann syndrome by targeted MS-MLPA analysis and nine cases with heterozygous pathogenic or likely pathogenic genetic variants by multigene analysis techniques ( FBN1 = 3, NSD1 = 2, NFIX = 1, SUZ12 = 1, CHD8 = 1, MC4R = 1). Three of 20 patients analyzed by WES had their diagnosis established. Only one non-syndromic patient had a definitive diagnosis. The sequential genetic assessment diagnosed 14 out of 42 (33.3%) tall patients. Conclusion: A systematic molecular approach of patients with tall stature was able to identify the etiology in 13 out of 30 (43.3%) syndromic and 1 out of 12 (8.3%) non-syndromic patients, contributing to the genetic counseling and avoiding unfavorable outcomes in the syndromic subgroup.