Clinical Characteristics of Pathogenic ACAN Variants and 3-Year Response to Growth Hormone Treatment: Real-World Data.

IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Hormone Research in Paediatrics Pub Date : 2024-01-01 Epub Date: 2024-01-17 DOI:10.1159/000535651
Judith S Renes, Ardine M J Reedijk, Monique Losekoot, Sarina G Kant, Manouk Van der Steen, Danielle C M Van der Kaay, Anita C S Hokken-Koelega, Hermine A Van Duyvenvoorde, Christiaan de Bruin
{"title":"Clinical Characteristics of Pathogenic ACAN Variants and 3-Year Response to Growth Hormone Treatment: Real-World Data.","authors":"Judith S Renes, Ardine M J Reedijk, Monique Losekoot, Sarina G Kant, Manouk Van der Steen, Danielle C M Van der Kaay, Anita C S Hokken-Koelega, Hermine A Van Duyvenvoorde, Christiaan de Bruin","doi":"10.1159/000535651","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Heterozygous variants in the ACAN gene may underlie disproportionate short stature with characteristically accelerated bone age (BA) maturation and/or early-onset osteoarthritis (OA).</p><p><strong>Methods: </strong>The objective of this study was to describe phenotype, analyze genotype-phenotype correlations, and assess the response of growth hormone (GH) treatment in children with a heterozygous ACAN variant. Thirty-six subjects (23 boys, 13 girls) with ACAN deficiency and treated for ≥1 year with GH were identified in the Dutch National Registry of GH treatment in children.</p><p><strong>Results: </strong>We identified 25 different heterozygous ACAN variants in 36 subjects. Median (interquartile range) height SDS at start of GH was -2.6 SDS (-3.2 to -2.2). Characteristic features such as disproportion, advanced BA, early-onset OA, and dysmorphic features like midface hypoplasia and brachydactyly were present in the majority of children, but in ∼20%, no specific features were reported. Subjects with a truncating ACAN variant had a shorter height SDS compared to subjects with a non-truncating variant (-2.8 SDS and -2.1 SDS, respectively, p = 0.002). After 3 years of GH, height gain SDS in prepubertal children was 1.0 SDS (0.9-1.4). In pubertal children, height SDS remained relatively stable.</p><p><strong>Conclusion: </strong>The phenotype of subjects with pathogenic heterozygous ACAN variants is highly variable, and genetic testing for ACAN deficiency should be considered in any child with significant short stature, even in the absence of disproportion, specific dysmorphic features, or BA advancement. Furthermore, children with ACAN deficiency may benefit from GH with a modest but significant response, which is sustained during 3 years of treatment.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hormone Research in Paediatrics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000535651","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/17 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction: Heterozygous variants in the ACAN gene may underlie disproportionate short stature with characteristically accelerated bone age (BA) maturation and/or early-onset osteoarthritis (OA).

Methods: The objective of this study was to describe phenotype, analyze genotype-phenotype correlations, and assess the response of growth hormone (GH) treatment in children with a heterozygous ACAN variant. Thirty-six subjects (23 boys, 13 girls) with ACAN deficiency and treated for ≥1 year with GH were identified in the Dutch National Registry of GH treatment in children.

Results: We identified 25 different heterozygous ACAN variants in 36 subjects. Median (interquartile range) height SDS at start of GH was -2.6 SDS (-3.2 to -2.2). Characteristic features such as disproportion, advanced BA, early-onset OA, and dysmorphic features like midface hypoplasia and brachydactyly were present in the majority of children, but in ∼20%, no specific features were reported. Subjects with a truncating ACAN variant had a shorter height SDS compared to subjects with a non-truncating variant (-2.8 SDS and -2.1 SDS, respectively, p = 0.002). After 3 years of GH, height gain SDS in prepubertal children was 1.0 SDS (0.9-1.4). In pubertal children, height SDS remained relatively stable.

Conclusion: The phenotype of subjects with pathogenic heterozygous ACAN variants is highly variable, and genetic testing for ACAN deficiency should be considered in any child with significant short stature, even in the absence of disproportion, specific dysmorphic features, or BA advancement. Furthermore, children with ACAN deficiency may benefit from GH with a modest but significant response, which is sustained during 3 years of treatment.

致病性 ACAN 变体的临床特征和生长激素治疗的 3 年反应:真实世界数据。
简介:ACAN基因杂合子变异可能是导致身材矮小不成比例、骨龄(BA)成熟加速和/或早发性骨关节炎(OA)的原因:本研究的目的是描述表型,分析基因型与表型的相关性,并评估杂合子 ACAN 变异儿童对生长激素(GH)治疗的反应。在荷兰全国儿童生长激素治疗登记处发现了36名患有ACAN缺乏症并接受生长激素治疗≥1年的受试者(23名男孩,13名女孩):结果:我们在 36 名受试者中发现了 25 种不同的 ACAN 杂合子变异。开始接受 GH 治疗时的身高 SDS 中位数(四分位数间距)为-2.6 SDS(-3.2 至 -2.2)。大多数患儿都有身材比例失调、BA提前、早发OA等特征,以及面中部发育不良和畸形等畸形特征,但20%的患儿没有具体特征。与具有非截断变异的受试者相比,具有ACAN截断变异的受试者身高SDS较短(分别为-2.8 SDS和-2.1 SDS,P = 0.002)。接受 3 年 GH 后,青春期前儿童的身高增长 SDS 为 1.0 SDS(0.9-1.4)。青春期儿童的身高 SDS 保持相对稳定:任何身材明显矮小的儿童,即使没有身材比例失调、特殊畸形特征或 BA 发育不良,也应考虑进行 ACAN 缺乏症的基因检测。此外,ACAN 缺乏症患儿可能会从 GH 中获益,并在 3 年的治疗过程中持续产生适度但显著的反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Hormone Research in Paediatrics
Hormone Research in Paediatrics ENDOCRINOLOGY & METABOLISM-PEDIATRICS
CiteScore
4.90
自引率
6.20%
发文量
88
审稿时长
4-8 weeks
期刊介绍: The mission of ''Hormone Research in Paediatrics'' is to improve the care of children with endocrine disorders by promoting basic and clinical knowledge. The journal facilitates the dissemination of information through original papers, mini reviews, clinical guidelines and papers on novel insights from clinical practice. Periodic editorials from outstanding paediatric endocrinologists address the main published novelties by critically reviewing the major strengths and weaknesses of the studies.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信