Cytogenetic anomalies are the predominant genetic alteration in children with nonfamilial tall stature: a comparative study with familial cases

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F25%3A10498864" target="_blank" >RIV/00216208:11130/25:10498864 - isvavai.cz</a>

Alternative codes found

RIV/00064203:_____/25:10498864

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=8RDuqS-bxv" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=8RDuqS-bxv</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00431-025-06256-9" target="_blank" >10.1007/s00431-025-06256-9</a>

Result language

angličtina

Original language name

Cytogenetic anomalies are the predominant genetic alteration in children with nonfamilial tall stature: a comparative study with familial cases

Original language description

The purpose of this study is to elucidate the genetic causes and phenotypic presentation of nonfamilial tall stature (nFTS) and to compare these findings with those of familial tall stature (FTS) from the same population that was previously studied. Children with nFTS (defined as a height &gt; + 2 SDs with both parents&apos; heights &lt; + 2 SDs) underwent endocrine and anthropometric examinations and genetic testing (karyotyping, SHOX gene dosage analysis and next-generation sequencing of 786 growth-associated genes). Exome sequencing was performed in patients with negative genetic results and a height &gt; + 3 SDs. A total of 55 children with nFTS were enrolled. The median height was + 2.8 SD (2.4-3.2 SD), and the median midparental height was + 0.7 SD (0.4-0.9 SD). Genetic causes of tall stature were identified in 6/55 (11%) children. Specifically, four children had gonosomal aneuploidy (47,XXY [2x], 47,XXX, 48,XXXX), one had a heterozygous complex rearrangement including SHOX gene duplication, and one carried a pathogenic variant in the TGFBR2 gene leading to Loeys-Dietz syndrome. A genetic cause of tall stature was significantly less common in nFTS (11%) than in our previously published cohort with FTS (32%). Conclusion: Cytogenetic abnormalities were the predominant genetic alteration identified in children with nFTS, confirming the justification of karyotype analysis in this cohort. The probability of genetic alterations was greater in children with FTS than in those with nFTS. Our findings suggest that the current guidelines for complex investigation are efficient for children with nFTS but need revision in children with FTS. What is known - what is new . Although tall stature is generally considered beneficial, it can be associated with health risks which need to be recognized in time. Tall stature without intellectual impairment is usually considered to be polygenic. . However, the cause of familial tall stature was monogenic more often than it was thought previously. . Children with non-familial and apparently non-syndromic tall stature have never been systematically investigated. . Monogenic causes of non-familial tall stature were observed in 11% of patients, including a participant with Loeys-Dietz syndrome.

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/NU21-07-00335" target="_blank" >NU21-07-00335: Analysis of genetic causes of overgrowth and assessment of related oncological, musculoskeletal and cardiovascular risks</a><br>

Continuities

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

Publication year

2025

Confidentiality

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

Name of the periodical

European Journal of Pediatrics

ISSN

0340-6199

e-ISSN

1432-1076

Volume of the periodical

184

Issue of the periodical within the volume

7

Country of publishing house

DE - GERMANY

Number of pages

9

Pages from-to

423

UT code for WoS article

001510013600002

EID of the result in the Scopus database

2-s2.0-105008576956