Genetic investigation of patients with tall stature

Edoarda Vasco de Albuquerque Albuquerque, Mariana Ferreira de Assis Funari, Elisângela Pereira de Souza Quedas, Rachel Sayuri Honjo Kawahira, Raquel Soares Jallad, Thais Kataoka Homma, Regina Martin, Vinícius Nahime Brito, Alexsandra C Malaquias, Antonio Marcondes Lerario, Carla Rosenberg, Ana Cristina Victorino Krepischi (+3 others)
2019 European Journal of Endocrinology  
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
more » ... ome 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 2 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 9 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.
doi:10.1530/eje-19-0785 pmid:31751304 fatcat:ruxbzf5k2rbetg2tnpzfsvkivm