Quélin Chloé, Loget Philippe, Rozel Céline, D'Hervé Dominique, Fradin Mélanie, Demurger Florence, Odent Sylvie, Pasquier Laurent, Cavé Hélène, Marcorelles Pascale
Service de Génétique Clinique, Centre de Référence Maladies Rares CLAD-Ouest, CHU Hôpital Sud, Rennes, France.
Service d'Anatomopathologie, CHU Pontchaillou, Rennes, France.
Eur J Med Genet. 2017 Jul;60(7):395-398. doi: 10.1016/j.ejmg.2017.03.014. Epub 2017 Apr 25.
Costello syndrome (CS) is a rare multiple congenital disorder caused by activating germline mutations in HRAS gene and is characterized by coarse facial features, severe feeding difficulties, failure to thrive, mild to severe intellectual disability, severe postnatal growth retardation, cardiac abnormalities or cancer predisposition. Phenotypic spectrum associated with HRAS mutations is broad, ranging from attenuated CS phenotype to neonatal and lethal forms with limited genotype-phenotype correlations. Congenital myopathy with neuromuscular spindle excess has been rarely described in the literature. We report a new severe fetal case of CS with distal arthrogryposis due to neuromuscular spindle excess, confirmed by the detection of the p.Gly12Val mutation in HRAS gene. This case emphasizes the fact that HRAS is the only gene responsible for neuromuscular spindle excess, underlines a correlation between p.Gly12Val mutation and severe CS phenotype and points out the importance of a muscle biopsy performed according to the suitable procedure in neuromuscular disorders for any fetal arthrogryposis.
科斯特洛综合征（CS）是一种罕见的多发性先天性疾病，由HRAS基因的种系激活突变引起，其特征是面部特征粗糙、严重喂养困难、生长发育迟缓、轻度至重度智力残疾、出生后严重生长发育迟缓、心脏异常或癌症易感性。与HRAS突变相关的表型谱很广，从轻度CS表型到新生儿和致死性形式，基因型与表型的相关性有限。文献中很少描述伴有神经肌肉纺锤体过多的先天性肌病。我们报告了一例新的严重胎儿CS病例，因神经肌肉纺锤体过多导致远端关节挛缩，通过检测HRAS基因中的p.Gly12Val突变得以确诊。该病例强调了HRAS是导致神经肌肉纺锤体过多的唯一基因这一事实，强调了p.Gly12Val突变与严重CS表型之间的相关性，并指出了在任何胎儿关节挛缩的神经肌肉疾病中，按照合适的程序进行肌肉活检的重要性。
