PDF(Pubmed)
Abstract：
Introduction: FATCO (Fibular Aplasia, Tibial Campomelia and Oligosyndactyly) is a very infrequent skeletal dysplasia classified within the limb hypoplasia-reduction defects group whose genetic cause has not yet been identified. The advent of next-generation sequencing is enabling the diagnosis of diseases with no previously known genetic cause. Methods: We performed a thorough autopsy on a fetus whose pregnancy was legally terminated due to severe malformations detected by ultrasound. A trio exome was run to identify the genetic cause and risk of recurrence. Previous literature of similar cases was systematically searched. Results: Anatomopathological analyses revealed complete fibular aplasia, shortened and campomelic tibia, absent ankle joint, club right foot and a split foot malformation, leading to the diagnosis of FATCO. Exome sequencing showed that the female fetus carried a de novo nonsense variant in DLX5. The literature search permitted the collection of information on 43 patients with FATCO, the majority of whom were males diagnosed postnatally. In most cases, lower limbs were affected exclusively, but in 39.5% of cases the upper limbs were also affected. Conclusion: The pathologies associated with DLX5 variants encompass a wide spectrum of manifestations ranging from abnormalities exclusively in the hands and feet to long bones such as the tibia and fibula.
摘要：
简介：FATCO（腓骨发育不全，胫骨弯曲型和少指型）是一种罕见的骨骼发育不良，属于肢体发育不全减少缺陷组，其遗传原因尚未确定。下一代测序的出现使得能够诊断没有先前已知的遗传原因的疾病。方法：我们对因超声检测到严重畸形而合法终止妊娠的胎儿进行了彻底的尸检。运行三外显子组以确定遗传原因和复发风险。系统检索了以前类似病例的文献。结果：解剖病理学分析显示完整腓骨发育不全，缩短和喜忧参半的胫骨，踝关节缺失，右脚和裂脚畸形，导致FATCO的诊断。外显子组测序显示雌性胎儿在DLX5中携带从头无义变体。文献检索允许收集43名FATCO患者的信息，其中大多数是出生后诊断的男性。在大多数情况下,下肢只受到影响，但在39.5%的病例中，上肢也受到影响。结论：与DLX5变异相关的病理包括广泛的表现，从仅在手和脚的异常到胫骨和腓骨等长骨。
