The increasing pace of gene discovery in the last decade has brought a major change in the way the genetic causes of brain malformations are being diagnosed. Unbiased genomic screening has gained the first place in the diagnostic protocol of a child with congenital (brain) anomalies and the detected variants are matched with the phenotypic presentation afterwards. This process is defined as “reverse phenotyping”. Screening of DNA, through copy number variant analysis of microarrays and analysis of exome data on different platforms, obtained from the index patient and both parents has become a routine approach in many centers worldwide. Clinicians are used to multidisciplinary team interaction in patient care and disease management and this explains why the majority of research that has led to the discovery of new genetic disorders nowadays proceeds from clinical observations to genomic analysis and to data exchange facilitated by open access sharing databases. However, the relevance of multidisciplinary team interaction has not been object of systematic research in the field of brain malformations. This review will illustrate some examples of how diagnostically driven questions through multidisciplinary interaction, among clinical and preclinical disciplines, can be successful in the discovery of new genes related to brain malformations. The first example illustrates the setting of interaction among neurologists, geneticists and neuro-radiologists. The second illustrates the importance of interaction among clinical dysmorphologists for pattern recognition of syndromes with multiple congenital anomalies. The third example shows how fruitful it can be to step out of the “clinical comfort zone”, and interact with basic scientists in applying emerging technologies to solve the diagnostic puzzles.

在过去十年中，基因发现的步伐不断加快，给大脑畸形的遗传原因的诊断方式带来了重大变化。无偏见的基因组筛查在先天性（大脑）异常儿童的诊断方案中占据首位，检测到的变异随后与表型表现相匹配。这个过程被定义为“反向表型”。通过微阵列的拷贝数变异分析和不同平台上的外显子组数据分析，从索引患者和父母双方获得的 DNA 筛选已成为全球许多中心的常规方法。临床医生习惯于在患者护理和疾病管理中进行多学科团队互动，这解释了为什么如今导致发现新遗传疾病的大多数研究都是从临床观察到基因组分析以及通过开放访问共享数据库促进的数据交换。然而，多学科团队互动的相关性尚未成为脑畸形领域系统研究的对象。这篇综述将说明一些例子，说明通过临床和临床前学科之间的多学科互动，诊断驱动的问题如何成功地发现与脑畸形相关的新基因。第一个例子说明了神经学家、遗传学家和神经放射学家之间相互作用的设置。第二个说明了临床畸形学家之间的相互作用对于具有多种先天性异常的综合征的模式识别的重要性。第三个例子展示了走出“临床舒适区”并与基础科学家互动应用新兴技术解决诊断难题的成果。