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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00064203:_____/25:10498864

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30209 - Paediatrics

Projekt

<a href="/cs/project/NU21-07-00335" target="_blank" >NU21-07-00335: Analýza genetických příčin vysokého vzrůstu a hodnocení souvisejících onkologických, muskuloskeletálních a kardiovaskulárních rizik</a><br>

Návaznosti

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

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

European Journal of Pediatrics

ISSN

0340-6199

e-ISSN

1432-1076

Svazek periodika

184

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

9

Strana od-do

423

Kód UT WoS článku

001510013600002

EID výsledku v databázi Scopus

2-s2.0-105008576956