Abstract：
OBJECTIVE: Chiari malformations (CMs) are a group of congenital or acquired disorders characterized by hindbrain overcrowding into an underdeveloped posterior cranial fossa. CM is considered largely sporadic-however, there exists growing evidence of transmissible genetic underpinnings. The purpose of this systematic review of all familial studies of CM was to investigate the existence of an inherited component and provide recommendations to manage and monitor at-risk family members.
METHODS: This paper includes the following: 1) a unique case report of dizygotic twins who presented at the Toronto Western Hospital Spinal Cord Clinic with symptomatic CM type 1 (CM-1) and syringomyelia; and 2) a systematic review of familial CM. The EMBASE and MEDLINE databases were searched on June 27, 2023, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only articles in the English language concerning the diagnosis of CM in > 1 human family member presented as a case study, case series, or literature review were included.
RESULTS: Among the 29 articles included in the final analysis, a total of 34 families with CM were analyzed. An average of 3 cases of CM were found per family among all generations. Eighty-one cases (88%) reported CM-1, whereas the other 11 (12%) cases reported either CM-0, CM-1.5, or tonsillar ectopia. A syrinx was present in 37 (54%) cases, with 14 (38%) of these patients also reporting a skeletal abnormality, the most common comorbidity. Most family members diagnosed with CM were siblings (18; 35%), followed by monozygotic twins/triplets (12; 23%).
CONCLUSIONS: Patients most often presented with headaches, sensory disturbances, or generalized symptoms. Overall, there exists mounting evidence for a hereditary component of CM. It is unlikely to be explained by a classic mendelian inheritance pattern, but is rather a polygenic architecture influenced by variable penetrance, cosegregation, and entirely nongenetic factors. For first-degree relatives of those affected by CM, the authors\' findings may influence clinicians to conduct closer clinical and radiographic monitoring, promote patient education, and consider earlier genetic testing.
METHODS: This paper includes the following: 1) a unique case report of dizygotic twins who presented at the Toronto Western Hospital Spinal Cord Clinic with symptomatic CM type 1 (CM-1) and syringomyelia; and 2) a systematic review of familial CM. The EMBASE and MEDLINE databases were searched on June 27, 2023, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only articles in the English language concerning the diagnosis of CM in > 1 human family member presented as a case study, case series, or literature review were included.
RESULTS: Among the 29 articles included in the final analysis, a total of 34 families with CM were analyzed. An average of 3 cases of CM were found per family among all generations. Eighty-one cases (88%) reported CM-1, whereas the other 11 (12%) cases reported either CM-0, CM-1.5, or tonsillar ectopia. A syrinx was present in 37 (54%) cases, with 14 (38%) of these patients also reporting a skeletal abnormality, the most common comorbidity. Most family members diagnosed with CM were siblings (18; 35%), followed by monozygotic twins/triplets (12; 23%).
CONCLUSIONS: Patients most often presented with headaches, sensory disturbances, or generalized symptoms. Overall, there exists mounting evidence for a hereditary component of CM. It is unlikely to be explained by a classic mendelian inheritance pattern, but is rather a polygenic architecture influenced by variable penetrance, cosegregation, and entirely nongenetic factors. For first-degree relatives of those affected by CM, the authors\' findings may influence clinicians to conduct closer clinical and radiographic monitoring, promote patient education, and consider earlier genetic testing.
摘要：
目的：Chiari畸形（CMs）是一组先天性或获得性疾病，其特征是后脑过度拥挤进入发育不全的后颅窝。CM被认为是零星的-然而，有越来越多的证据表明可传播的遗传基础。对CM的所有家族研究进行系统回顾的目的是调查遗传成分的存在，并提供管理和监测高危家庭成员的建议。
方法：本文包括以下内容：1）在多伦多西部医院脊髓诊所就诊的双卵双胞胎的独特病例报告，有症状的CM1型（CM-1）和脊髓空洞症；2）对家族性CM的系统评价。根据系统审查和荟萃分析（PRISMA）指南的首选报告项目，于2023年6月27日检索了EMBASE和MEDLINE数据库。只有关于在>1人类家庭成员中CM诊断的英文文章作为案例研究，案例系列,或文献综述被纳入。
结果：在最终分析的29篇文章中，共分析了34个CM家庭。在所有世代中，每个家庭平均发现3例CM。81例（88％）报告CM-1，而其他11例（12％）报告CM-0，CM-1.5或扁桃体异位。37例（54％）病例中存在syrinx，其中14例（38%）患者也报告骨骼异常，最常见的合并症。大多数被诊断为CM的家庭成员是兄弟姐妹（18;35％），其次是单卵双胞胎/三胞胎（12;23％）。
结论：患者最常出现头痛，感觉障碍,或全身症状。总的来说,有越来越多的证据表明CM的遗传成分。这不太可能用经典的孟德尔继承模式来解释，而是一种受可变外显率影响的多基因结构，共隔离，和完全非遗传因素。对于受CM影响的一级亲属，作者的发现可能会影响临床医生进行更密切的临床和影像学监测，促进患者教育，并考虑早期的基因检测。
方法：本文包括以下内容：1）在多伦多西部医院脊髓诊所就诊的双卵双胞胎的独特病例报告，有症状的CM1型（CM-1）和脊髓空洞症；2）对家族性CM的系统评价。根据系统审查和荟萃分析（PRISMA）指南的首选报告项目，于2023年6月27日检索了EMBASE和MEDLINE数据库。只有关于在>1人类家庭成员中CM诊断的英文文章作为案例研究，案例系列,或文献综述被纳入。
结果：在最终分析的29篇文章中，共分析了34个CM家庭。在所有世代中，每个家庭平均发现3例CM。81例（88％）报告CM-1，而其他11例（12％）报告CM-0，CM-1.5或扁桃体异位。37例（54％）病例中存在syrinx，其中14例（38%）患者也报告骨骼异常，最常见的合并症。大多数被诊断为CM的家庭成员是兄弟姐妹（18;35％），其次是单卵双胞胎/三胞胎（12;23％）。
结论：患者最常出现头痛，感觉障碍,或全身症状。总的来说,有越来越多的证据表明CM的遗传成分。这不太可能用经典的孟德尔继承模式来解释，而是一种受可变外显率影响的多基因结构，共隔离，和完全非遗传因素。对于受CM影响的一级亲属，作者的发现可能会影响临床医生进行更密切的临床和影像学监测，促进患者教育，并考虑早期的基因检测。
