Geleophysic and acromicric dysplasias: natural history, genotype–phenotype correlations, and management guidelines from 38 cases,Genetics in Medicine

当前位置： X-MOL 学术 › Genet. Med. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Geleophysic and acromicric dysplasias: natural history, genotype–phenotype correlations, and management guidelines from 38 cases
Genetics in Medicine ( IF 6.6 ) Pub Date : 2020-10-21 , DOI: 10.1038/s41436-020-00994-x
Pauline Marzin _{1,

2} , Briac Thierry _{3,

4} , Andrea Dancasius _{1,

2} , Anne Cavau ₁ , Caroline Michot _{1,

2} , Sophie Rondeau _{1,

2} , Geneviève Baujat _{1,

2} , Gilles Phan ₅ , Maryse Bonnière ₆ , Muriel Le Bourgeois ₇ , Diala Khraiche ₈ , Zagorka Pejin ₉ , Damien Bonnet _{8,

10} , Christophe Delacourt ₇ , Valérie Cormier-Daire _{1,

2}

Affiliation

Purpose

Geleophysic dysplasia (GD) and acromicric dysplasia (AD) are characterized by short stature, short extremities, and progressive joint limitation. In GD, cardiorespiratory involvement can result in poor prognosis. Dominant variants in the FBN1 and LTBP3 genes are responsible for AD or GD, whereas recessive variants in the ADAMTSL2 gene are responsible for GD only. The aim of this study was to define the natural history of these disorders and to establish genotype–phenotype correlations.

Methods

This monocentric retrospective study was conducted between January 2008 and December 2018 in a pediatric tertiary care center and included patients with AD or GD with identified variants (FBN1, LTBP3, or ADAMTSL2).

Results

Twenty-two patients with GD (12 ADAMTSL2, 8 FBN1, 2 LTBP3) and 16 patients with AD (15 FBN1, 1 LTBP3) were included. Early death occurred in eight GD and one AD. Among GD patients, 68% presented with heart valve disease and 25% developed upper airway obstruction. No AD patient developed life-threatening cardiorespiratory issues. A greater proportion of patients with either a FBN1 cysteine variant or ADAMTSL2 variants had a poor outcome.

Conclusion

GD and AD are progressive multisystemic disorders with life-threatening complications associated with specific genotype. A careful multidisciplinary follow-up is needed.

中文翻译：

Geleophysic 和 acromicric 发育不良：38 例病例的自然史、基因型-表型相关性和管理指南

目的

Geleophysic 发育不良 (GD) 和肢端发育不良 (AD) 的特征是身材矮小、四肢短和进行性关节受限。在GD中，心肺受累可导致预后不良。FBN1和LTBP3基因中的显性变体负责 AD 或 GD，而ADAMTSL2基因中的隐性变体仅负责 GD。本研究的目的是确定这些疾病的自然史并建立基因型-表型相关性。

方法

这项单中心回顾性研究于 2008 年 1 月至 2018 年 12 月在儿科三级护理中心进行，纳入了具有已确定变异（FBN1、LTBP3或ADAMTSL2）的 AD 或 GD 患者。

结果

包括22名GD患者（12名ADAMTSL2、8名FBN1、2名LTBP3）和16名AD患者（15名FBN1、1名LTBP3 ）。早期死亡发生在 8 名 GD 和 1 名 AD 中。在 GD 患者中，68% 出现心脏瓣膜疾病，25% 出现上气道阻塞。没有 AD 患者出现危及生命的心肺问题。更大比例的FBN1半胱氨酸变异或ADAMTSL2变异的患者预后不良。