性发育不良(GD)和性腺发育不良(AD)的特征是身材矮小,四肢短,和渐进的联合限制。在GD,心肺受累可导致预后不良。FBN1和LTBP3基因中的显性变异体负责AD或GD,而ADAMTSL2基因中的隐性变异仅负责GD。这项研究的目的是定义这些疾病的自然史,并建立基因型-表型相关性。
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,包括患有AD或GD的患者,这些患者具有确定的变异(FBN1,LTBP3或ADAMTSL2)。
包括22例GD患者(12例ADAMTSL2,8例FBN1,2例LTBP3)和16例AD患者(15例FBN1,1例LTBP3)。早期死亡发生在8例GD和1例AD中。在GD患者中,68%的人患有心脏瓣膜疾病,25%的人患有上呼吸道阻塞。没有AD患者出现危及生命的心肺问题。具有FBN1半胱氨酸变体或ADAMTSL2变体的患者中,有较高比例的患者预后较差。
GD和AD是具有与特定基因型相关的危及生命的并发症的进行性多系统疾病。需要认真的多学科后续行动。
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.
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).
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.
GD and AD are progressive multisystemic disorders with life-threatening complications associated with specific genotype. A careful multidisciplinary follow-up is needed.