Kroeldrup Lone, Larsen Lisbeth A, Fagerberg Christina, Hertz Jens M, Christensen Kaare
Department of Clinical Genetics,Odense University Hospital,Odense C,Denmark.
Epidemiology, Biostatistics and Biodemography,Department of Public Health,Faculty of Health Science,University of Southern Denmark,Odense C,Denmark.
Twin Res Hum Genet. 2017 Jun;20(3):216-225. doi: 10.1017/thg.2017.17. Epub 2017 May 9.
Hall (Embryologic development and monozygotic twinning. Acta Geneticae Medicae et Gemellologiae, Vol. 45, 1996, pp. 53-57) hypothesized that chromosomal aberrations can lead to monozygotic (MZ) twinning. However, twinning and chromosomal aberrations increase prenatal mortality and could reduce the prevalence of chromosomal aberrations in live-born twins. We compared prevalence proportion ratios (PPR) of chromosomal aberrations and trisomy 21 (T21) in live-born twins versus singletons born in Denmark during 1968-2009.
We linked the Danish Twin Registry and a 5% random sample of all singletons to the Danish Cytogenetic Central Register and calculated PPR adjusted for maternal age for MZ, dizygotic (DZ), and all twins versus singletons. Zygosity was based on questionnaires or genetic markers.
No overall difference in risk of chromosomal aberrations or T21 in twins versus singletons was found. PPR in MZ and DZ twins was 0.87 (95% CI [0.60, 1.27]) and 1.05 (95% CI [0.88, 1.27]), respectively. For T21 there was a tendency to a lower prevalence in MZ twins compared to singletons (PPR: 0.29, 95% CI [0.07, 1.14]), whereas PPR was significantly increased in DZ twins (1.62, 95% CI [1.20, 2.19]). The observed proportion of MZ twin pairs among twin pairs with aberrations (0.22, 95% CI [0.16, 0.28]) was significantly lower than the proportion expected from the Weinberg method (0.32, 95% CI [CI, 0.26, 0.39]).
Based on databases providing complete national coverage on twins with chromosomal aberrations, we found no overall difference in risk of chromosomal aberrations or T21 in twins versus singletons. Around conception twins may have an increased risk of chromosomal aberrations, but loss of especially MZ embryos could lead to similar risk among live-born twins and singletons.
霍尔（《胚胎发育与单卵双胎。医学遗传学与双胎学学报》，第45卷，1996年，第53 - 57页）推测染色体畸变可导致单卵（MZ）双胎。然而，双胎妊娠和染色体畸变会增加产前死亡率，且可能降低活产双胎中染色体畸变的发生率。我们比较了1968 - 2009年丹麦出生的活产双胎与单胎中染色体畸变及21三体（T21）的患病率比例（PPR）。
我们将丹麦双胎登记处与所有单胎的5%随机样本与丹麦细胞遗传学中央登记处进行关联，并计算了经母亲年龄调整后的MZ、双卵（DZ）及所有双胎与单胎的PPR。双胎类型基于问卷或基因标记确定。
未发现双胎与单胎在染色体畸变或T21风险上存在总体差异。MZ和DZ双胎的PPR分别为0.87（95%可信区间[0.60, 1.27]）和1.05（95%可信区间[0.88, 1.27]）。对于T21，与单胎相比，MZ双胎的患病率有降低趋势（PPR：0.29，95%可信区间[0.07, 1.14]），而DZ双胎的PPR显著升高（1.62，95%可信区间[1.20, 2.19]）。在有染色体畸变的双胎对中观察到的MZ双胎对比例（0.22，95%可信区间[0.16, 0.28]）显著低于温伯格方法预期的比例（0.32，95%可信区间[0.26, 0.39]）。
基于提供全国范围内完整染色体畸变双胎数据的数据库，我们发现双胎与单胎在染色体畸变或T21风险上无总体差异。在受孕前后，双胎可能有更高的染色体畸变风险，但尤其是MZ胚胎的丢失可能导致活产双胎和单胎有相似的风险。
