背景:Weill-Marchesani综合征(WMS)属于肢端发育不良,由身材矮小定义,短指和关节限制。WMS的特征是特定的眼科异常,尽管心血管缺陷也有报道。FBN1的单等位基因变异与WMS的主要形式有关,而ADAMTS10,ADAMTS17和LTBP2的双等位基因变异是WMS的隐性形式。
目的:WMS的自然史描述和基因型-表型相关性的建立。
方法:回顾性多中心研究和文献综述。
方法:WMS的临床诊断与已确定的致病变异。
结果:包括61例患者:18例来自我们的队列,43例来自文献。21在ADAMTS17中具有变体,在FBN1中具有19,在ADAMTS10中具有19,在LTBP2中具有2。所有出现眼睛异常的人,主要是天疱疮(42/61)和外翻(39/61)。73%的人身材矮小(从-2.2到-5.5SD),10/61例患者有瓣膜病。关于FBN1变体,具有位于转化生长因子(TGF)-β结合蛋白样结构域5(TB5)结构域的变异体的患者显著小于TB5结构域外具有FBN1变异体的患者(p=0.0040).
结论:除了眼科发现,这是诊断的强制性要求,WMS的表型似乎比最初描述的更具可变性,部分由基因型-表型相关性解释。
BACKGROUND: Weill-Marchesani syndrome (WMS) belongs to the group of acromelic dysplasias, defined by short stature, brachydactyly and joint limitations. WMS is characterised by specific ophthalmological abnormalities, although cardiovascular defects have also been reported. Monoallelic variations in FBN1 are associated with a dominant form of WMS, while biallelic variations in ADAMTS10, ADAMTS17 and LTBP2 are responsible for a recessive form of WMS.
OBJECTIVE: Natural history description of WMS and genotype-phenotype correlation establishment.
METHODS: Retrospective multicentre study and literature
review.
METHODS: clinical diagnosis of WMS with identified pathogenic variants.
RESULTS: 61 patients were included: 18 individuals from our cohort and 43 patients from literature. 21 had variants in ADAMTS17, 19 in FBN1, 19 in ADAMTS10 and 2 in LTBP2. All individuals presented with eye anomalies, mainly spherophakia (42/61) and ectopia lentis (39/61). Short stature was present in 73% (from -2.2 to -5.5 SD), 10/61 individuals had valvulopathy. Regarding FBN1 variants, patients with a variant located in transforming growth factor (TGF)-β-binding protein-like domain 5 (TB5) domain were significantly smaller than patients with FBN1 variant outside TB5 domain (p=0.0040).
CONCLUSIONS: Apart from the ophthalmological findings, which are mandatory for the diagnosis, the phenotype of WMS seems to be more variable than initially described, partially explained by genotype-phenotype correlation.