Pediatric and perinatal stroke can present as an early symptom in undiagnosed syndromes characterized by simple Mendelian inheritance. In order to diagnose those patients affected with a monogenic disorder in which an arterial cerebrovascular event or arteriopathy may have preceded any other specific symptom, we aimed to establish and validate a targeted gene panel, and to determine its diagnostic yield and clinical utility. To this end, thirty-eight patients were selected with heterogeneous cryptogenic stroke phenotypes, mostly including multiple and recurrent ischemic or hemorrhagic arterial strokes and porencephalies, variably associated with calcifications, intracranial or systemic steno-occlusive arteriopathies, positive family history, and syndromic conditions. Clinical and neuroradiological data were collected for every patient enrolled in the study, and DNA samples were tested by means of a customized gene panel including 15 genes associated with known genetic diseases related to pediatric stroke. In four patients (10.5%) the analyses unraveled pathogenetic variants in ABCC6 and COL4A1 genes, leading to a definite genetic diagnosis with a great beneficial impact on patients management, while results were null in the remaining patients. These findings suggest a high complexity and variability of the included stroke phenotypes, that could not be fully accounted for by the genes tested in the present study. A wider gene panel or an unbiased genomic approach may be better suited and advisable to explain a greater proportion of pediatric and perinatal stroke events.

小儿和围产期中风可表现为以简单孟德尔遗传为特征的未诊断综合征的早期症状。为了诊断那些患有单基因疾病的患者，在该疾病中，可能在任何其他特定症状之前出现了动脉脑血管事件或动脉病变，我们的目标是建立和验证靶向基因组，并确定其诊断结果和临床实用性。为此，选择了38例具有异源性隐源性卒中表型的患者，主要包括多发性和复发性缺血性或出血性中风和孔隙性脑梗死，并伴有钙化，颅内或全身性狭窄闭塞性动脉病变，阳性家族史和综合征。收集了该研究的每位患者的临床和神经放射学数据，并通过定制的基因组检测了DNA样品，该基因组包括与小儿卒中相关的已知遗传疾病相关的15个基因。在4例（10.5％）患者中，分析揭示了ABCC6和COL4A1基因可进行明确的遗传学诊断，对患者的治疗产生巨大的有益影响，而其余患者的结果则为零。这些发现表明所包含的中风表型具有很高的复杂性和可变性，而在本研究中测试的基因不能完全说明这一点。较宽泛的基因组或无偏见的基因组方法可能更适合并建议用于解释更大比例的儿科和围产期中风事件。