PDF(Pubmed)
Abstract：
Cornelia de Lange syndrome (CdLS) is a rare neurodevelopmental disorder characterized by distinct dysmorphic facies, skeletal anomalies, and failure to thrive. CdLS type 5 (CdLS5) is caused by the HDAC8 gene mutations on chromosome Xq13.1 with X-linked dominant inheritance. We report our observation of an individual with CdLS5 with de novo missense mutation presenting with a novel phenotype of generalized dystonia. A four-month-old girl, second born to a non-consanguineous couple, presented with developmental delay, failure to thrive, and spastic quadriparesis. She had a history of intrauterine growth retardation in the third trimester of pregnancy. Facial gestalt was suggestive of CdLS. She had marked axial and appendicular dystonia. A skeletal survey and magnetic resonance imaging (MRI) with magnetic resonance spectroscopy (MRS) brain studies were normal. Genetic testing revealed a heterozygous missense variation c.628G>C in the HDAC8 gene. She was treated with trihexyphenidyl and clonazepam, followed by syndopa. On follow-up assessment at 22 months of age, the dystonia gradually improved but not entirely over time with medication. It is already known that single gene disorders, including SCN1A, SCN2A, KCNQ2, PRRT2, and pyridoxine deficiency, can result in isolated dystonia; we add CdLS5 (HDAC8 variation) to this expanding spectrum.
摘要：
CorneliadeLange综合征（CdLS）是一种罕见的神经发育障碍，其特征是明显的畸形相，骨骼异常,未能茁壮成长。CdLS5型（CdLS5）是由具有X连锁显性遗传的Xq13.1染色体上的HDAC8基因突变引起的。我们报告了我们对CdLS5个体的观察，该个体具有从头错义突变，呈现出一种新型的全身性肌张力障碍表型。一个四个月大的女孩,第二个出生在一对非近亲的夫妇身上，出现发育迟缓，未能茁壮成长，和痉挛性四肢瘫痪.她在妊娠晚期有宫内发育迟缓的病史。面形塔提示CdLS。她有明显的轴向和阑尾肌张力障碍。骨骼检查和磁共振成像（MRI）以及磁共振波谱（MRS）脑部研究均正常。遗传检测显示HDAC8基因中存在杂合错义变异c.628G>C。她接受了苯并苯三甲和氯硝西泮的治疗,其次是辛多巴。在22个月大的随访评估中，肌张力障碍逐渐改善，但并不完全随着药物治疗的时间。已知单基因疾病,包括SCN1A,SCN2A,KCNQ2、PRRT2和吡哆醇缺乏症，可以导致孤立的肌张力障碍;我们将CdLS5(HDAC8变异)添加到这个扩展的光谱中。
