Role of genetic investigation in the diagnosis of short stature in a cohort of Italian children.

Autor:	Cavarzere P; Pediatric Division, Department of Pediatrics, University Hospital of Verona (Full Member of European Reference Network Endo-ERN), Verona, Italy. paolocavarzere@yahoo.it.; Department of Pediatrics, Child and Mother's Hospital, Piazzale Stefani 1, 37126, Verona, Italy. paolocavarzere@yahoo.it., Pietrobelli A; Pediatric Division, Department of Pediatrics, University Hospital of Verona (Full Member of European Reference Network Endo-ERN), Verona, Italy.; Department Surgical Sciences, Dentistry, Gynecology and Pediatrics, Pediatric Clinic, University of Verona, Verona, Italy., Gandini A; Department Surgical Sciences, Dentistry, Gynecology and Pediatrics, Pediatric Clinic, University of Verona, Verona, Italy., Munari S; Pediatric Division, Department of Pediatrics, University Hospital of Verona (Full Member of European Reference Network Endo-ERN), Verona, Italy., Baffico AM; Laboratory of Human Genetics, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Maffei M; Laboratory of Human Genetics, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Gaudino R; Pediatric Division, Department of Pediatrics, University Hospital of Verona (Full Member of European Reference Network Endo-ERN), Verona, Italy.; Department Surgical Sciences, Dentistry, Gynecology and Pediatrics, Pediatric Clinic, University of Verona, Verona, Italy., Guzzo A; Laboratory Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy., Arrigoni M; Pediatric Division, Department of Pediatrics, University Hospital of Verona (Full Member of European Reference Network Endo-ERN), Verona, Italy., Coviello D; Laboratory of Human Genetics, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Piacentini G; Pediatric Division, Department of Pediatrics, University Hospital of Verona (Full Member of European Reference Network Endo-ERN), Verona, Italy.; Department Surgical Sciences, Dentistry, Gynecology and Pediatrics, Pediatric Clinic, University of Verona, Verona, Italy., Antoniazzi F; Pediatric Division, Department of Pediatrics, University Hospital of Verona (Full Member of European Reference Network Endo-ERN), Verona, Italy.; Department Surgical Sciences, Dentistry, Gynecology and Pediatrics, Pediatric Clinic, University of Verona, Verona, Italy.; Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Regional Center for the Diagnosis and Treatment of Children and Adolescents with Rare Skeletal Disorders, Pediatric Clinic, University of Verona, Verona, Italy.
Jazyk:	angličtina
Zdroj:	Journal of endocrinological investigation [J Endocrinol Invest] 2024 May; Vol. 47 (5), pp. 1237-1250. Date of Electronic Publication: 2023 Dec 12.
DOI:	10.1007/s40618-023-02243-9
Abstrakt:	Background: Short stature (SS) is defined as height more than 2 standard deviations below the mean for age and sex. Hypothyroidism, celiac disease, growth hormone deficiency, hormonal abnormalities, and genetic conditions are among its causes. A wide range of conditions often due to largely unknown genetic variants can elude conventional diagnostic workup. Aim: We used next-generation sequencing (NGS) to better understand the etiology of SS in a cohort of Italian children. Patients and Methods: The study sample was 125 children with SS of unknown origin referred to our Institute between 2015 and 2021. All had undergone complete auxological and hormonal investigations to exclude common causes of SS. Genetic analysis was performed using a NGS panel of 104 genes. Clinical data were reviewed to clarify the pathogenicity of the variants detected. Results: In this cohort, 43 potentially causing variants were identified in 38 children. A syndromic genetic condition was diagnosed in 7: Noonan syndrome in 3, Leri-Weill syndrome in 3, and hypochondroplasia in 1. Moreover, 8 benign variants and other 37 like benign variants were found. In 88 children, 179 variants of uncertain significance (VUS) were identified. No variant was found in 16 children. Conclusion: Genetic analysis is a useful tool in the diagnostic workup of patients with SS, in adapting management and treatment, and in identifying syndromes with mild atypical clinical features. The role of VUS should not be underestimated, particularly when multiple VUS with possible mutual worsening effects are present in the same child. (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)
Databáze:	MEDLINE
Externí odkaz:	Full text from SpringerLink