Prenatal Pediatrics Institute, Children's National Hospital, Washington, District of Columbia, USA.
George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Prenat Diagn. 2021 May;41(6):778-790. doi: 10.1002/pd.5909. Epub 2021 Feb 26.
Report a single-center 12-year experience in the fetal diagnosis of diencephalic-mesencephalic junction dysplasia (DMJD) to expand the phenotype with Magnetic resonance imaging (MRI)-based classification, evaluate genetic etiologies, and ascertain outcomes.
Retrospective medical record and imaging review of all fetal MRI exams with DMJD were performed at our institution.
Thirty-three pregnancies with fetal MRI findings of DMJD at 24 (18-37) weeks gestational age were studied; 70% were referred for fetal hydrocephalus. Three fetal MRI patterns were recognized. Type A (butterfly/hypothalamus-midbrain union) was seen in two cases (6%), Type B (partial thalamus-midbrain union) in 22 fetuses (70%), and Type C (complete/near complete midbrain-thalamic continuity) in nine fetuses (24%). L1CAM mutations were identified in four cases, and biallelic VRK1 variants in another. Among 14 live-born cases, 11 survived infancy, and 10 underwent postnatal brain MRI which confirmed the fetal MRI diagnosis in all but one case. Development was delayed in all surviving infants, most with additional neurological sequelae.
DMJD may be identified by prenatal MRI as early as 18 weeks gestation. We propose three distinct phenotypic forms of DMJD, Types A-C. Next-generation sequencing provides an underlying molecular diagnosis in some patients, but further studies on associated genetic diagnoses and clinical outcomes are indicated.
报告单中心 12 年来对间脑-中脑连接发育不良（DMJD）的胎儿诊断经验，通过磁共振成像（MRI）为基础的分类扩展表型，评估遗传病因，并确定结局。
对我院所有胎儿 MRI 检查中发现 DMJD 的病例进行回顾性病历和影像学回顾。
33 例妊娠在 24 周（18-37 周）时行胎儿 MRI 检查发现 DMJD，70%因胎儿脑积水而转诊。发现 3 种胎儿 MRI 模式。A型（蝴蝶/下丘脑-中脑联合）见于 2 例（6%），B 型（部分丘脑-中脑联合）见于 22 例胎儿（70%），C 型（完全/近完全中脑-丘脑连续性）见于 9 例胎儿（24%）。4 例发现 L1CAM 突变，另 1 例发现 VRK1 双等位基因突变。14 例活产儿中，11 例存活至婴儿期，10 例接受了产后脑部 MRI 检查，除 1 例外，所有病例均证实了胎儿 MRI 诊断。所有存活婴儿的发育均延迟，大多数伴有额外的神经后遗症。
DMJD 可在妊娠 18 周时通过产前 MRI 识别。我们提出了 DMJD 的 3 种不同表型形式，A 型-C 型。下一代测序为一些患者提供了潜在的分子诊断，但需要进一步研究相关的遗传诊断和临床结局。
