Kobets Andrew, Lee Ryan P, Oriko David, Jackson Eric, Robinson Shenandoah, Cohen Alan, Groves Mari L
Division of Pediatric Neurosurgery, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Division of Pediatric Neurosurgery, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA,
Pediatr Neurosurg. 2020;55(6):363-373. doi: 10.1159/000511365. Epub 2020 Dec 2.
Despite folate supplementation, neural tube defects (NTDs) still occur in 0.5-1.0/1,000 pregnancies, with 30-50% not preventable with folate. Twinning has increased due to artificial fertilization and in itself predisposes to NTDs at a rate of 1.6/1,000. The contributions of genetic and environmental factors to myelomeningocele development remain poorly understood. Expression patterns of congenital pathologies in twins can sometimes provide etiological insight. Concordance of NTDs in twins is 0.03/1,000, with dual myelomeningocele reported in only 23 pairs, only one of which survived. We present the 24th pair, the 1st to maintain lower extremity motor function. We review all prior cases and discuss implications of twin concordance on the interplay of genetic and environmental influences. Case Report and Review: A new case of female monozygotic twins born to a well-nourished 24-year-old female is reported with details of perioperative care. Prenatal ultrasound showed L3-S4 and L5-S4 myelomeningoceles, Chiari II malformations, and ventriculomegaly. Copy number microarray was unrevealing. Each underwent uncomplicated repair on day of life 1, and ventriculoperitoneal shunt placement on days of life 10 and 16. Both had movement in the legs upon 6-week follow-up. All prior reported cases of concordant twin myelomeningoceles were abstracted and analyzed, revealing persistence of occurrence despite folate supplementation and a majority occurring in dizygotic pairs. The literature is also reviewed to summarize current knowledge of myelomeningocele pathophysiology as it relates to genetic and environmental influences.
Meticulous surgical and perioperative care allowed for early positive outcomes in each twin. However, etiopathogenesis remains elusive. In general, only of a minority of cases have underlying genetic lesions or clear environmental triggers. Concordance in monozygotic twins argues for a strong genetic influence; yet, literature review reveals a higher rate of concordant dizygotic twins. This, along with the observation of differing resultant phenotypes in monozygotic twins as seen in this case, prompts further investigation into nonfolate environmental influences. While efforts in genetic investigation should continue, the role of teratogens and exposures should not be minimized in research efforts, public health, and family counseling. Clinical genetic testing remains of limited utility in the majority of patients until more is known.
尽管补充了叶酸，但神经管缺陷（NTDs）仍以每1000例妊娠中有0.5 - 1.0例的发生率出现，其中30 - 50%的病例无法通过叶酸预防。由于人工受精，双胞胎的数量有所增加，而双胞胎本身患神经管缺陷的发生率为每1000例中有1.6例。遗传和环境因素对脊髓脊膜膨出发展的影响仍知之甚少。双胞胎中先天性疾病的表达模式有时能提供病因学线索。双胞胎中神经管缺陷的一致性为每1000例中有0.03例，仅报告了23对双胞胎患有双侧脊髓脊膜膨出，其中只有一对存活。我们报告第24对双胞胎，这是第一对维持下肢运动功能的双胞胎。我们回顾了所有先前的病例，并讨论了双胞胎一致性对遗传和环境影响相互作用的意义。病例报告与综述：报告了一例新的女性单卵双胞胎病例，其母亲为一名营养良好的24岁女性，并详细介绍了围手术期护理情况。产前超声显示L3 - S4和L5 - S4脊髓脊膜膨出、Chiari II型畸形和脑室扩大。拷贝数微阵列检测未发现异常。两人均在出生第1天接受了简单的修复手术，并分别在出生第10天和第16天进行了脑室腹腔分流术。6周随访时两人腿部均有活动。对所有先前报道的双胞胎脊髓脊膜膨出一致病例进行了摘要和分析，结果显示尽管补充了叶酸，但该疾病仍有发生，且大多数病例发生在双卵双胞胎中。还对相关文献进行了综述，以总结目前关于脊髓脊膜膨出病理生理学与遗传和环境影响相关的知识。
精心的手术和围手术期护理使每对双胞胎都取得了早期良好的结果。然而，病因发病机制仍然不明。一般来说，只有少数病例有潜在的遗传病变或明确的环境触发因素。单卵双胞胎的一致性表明遗传影响很大；然而，文献综述显示双卵双胞胎的一致性发生率更高。结合本病例中观察到的单卵双胞胎出现不同的最终表型，这促使进一步研究非叶酸环境影响因素。虽然基因研究应继续进行，但在研究工作、公共卫生和家庭咨询中，致畸物和暴露因素的作用不应被忽视。在了解更多情况之前，临床基因检测在大多数患者中的作用仍然有限。
