Isolated growth hormone deficiency in children with vertically transmitted short stature: What do the genes tell us?

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F23%3A10455092" target="_blank" >RIV/00216208:11130/23:10455092 - isvavai.cz</a>

Alternative codes found

RIV/00064203:_____/23:10455092

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=oItzsWhVJa" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=oItzsWhVJa</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fendo.2022.1102968" target="_blank" >10.3389/fendo.2022.1102968</a>

Result language

angličtina

Original language name

Isolated growth hormone deficiency in children with vertically transmitted short stature: What do the genes tell us?

Original language description

Introduction: The growth hormone deficiency (GHD) diagnosis is controversial especially due to low specificity of growth hormone (GH) stimulation tests. It is therefore believed that children diagnosed with GHD form a heterogeneous group with growth disorder frequently independent on GH function. No study evaluating the complex etiology of growth failure in children with diagnosed GHD has been performed thus far. Aims: To discover genetic etiology of short stature in children with diagnosed GHD from families with short stature. Methods: Fifty-two children diagnosed with primary GHD and vertically transmitted short stature (height SDS in the child and his/her shorter parent &lt;-2 SD) were included to our study. The GHD diagnosis was based on growth data suggestive of GHD, absence of substantial disproportionality (sitting height to total height ratio &lt;-2 SD or &gt;+2 SD), IGF-1 levels &lt;0 for age and sex specific SD and peak GH concentration &lt;10 ug/L in two stimulation tests. All children were examined using next-generation sequencing methods, and the genetic variants were subsequently evaluated by American College of Medical Genetics standards and guidelines. Results: The age of children at enrollment into the study was 11 years (median, IQR 9-14 years), their height prior to GH treatment was -3.0 SD (-3.6 to -2.8 SD), IGF-1 concentration -1.4 SD (-2.0 to -1.1 SD), and maximal stimulated GH 6.3 ug/L (4.8-7.6 ug/L). No child had multiple pituitary hormone deficiency or a midbrain region pathology. Causative variant in a gene that affects growth was discovered in 15/52 (29%) children. Of them, only 2 (13%) had a genetic variant affecting GH secretion or function (GHSR and OTX2). Interestingly, in 10 (67%) children we discovered a primary growth plate disorder (ACAN, COL1A2, COL11A1, COL2A1, EXT2, FGFR3, NF1, NPR2, PTPN11 [2x]), in one (7%) a genetic variant impairing IGF-1 action (IGFALS) and in two (12%) a variant in miscellaneous genes (SALL4, MBTPS2). Conclusions: In children with vertically transmitted short stature, genetic results frequently did not correspond with the clinical diagnosis of GH deficiency. These results underline the doubtful reliability of methods standardly used to diagnose GH deficiency.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30209 - Paediatrics

Project

<a href="/en/project/NU22J-07-00014" target="_blank" >NU22J-07-00014: Elucidating the etiopathogenesis of a growth disorder in children with clinically diagnosed growth hormone deficiency using modern genetic methods as a way to optimize the diagnostics and the treatment</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in Endocrinology

ISSN

1664-2392

e-ISSN

—

Volume of the periodical

13

Issue of the periodical within the volume

January

Country of publishing house

CH - SWITZERLAND

Number of pages

7

Pages from-to

1102968

UT code for WoS article

000920798900001

EID of the result in the Scopus database

2-s2.0-85147098316