Roosenboom Jasmien, Indencleef Karlijne, Hens Greet, Peeters Hilde, Christensen Kaare, Marazita Mary L, Claes Peter, Leslie Elizabeth J, Weinberg Seth M
Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Electrical Engineering, ESAT/PSI, KU Leuven, Leuven, Belgium.
Am J Med Genet A. 2017 Nov;173(11):2886-2892. doi: 10.1002/ajmg.a.38471. Epub 2017 Sep 8.
Nonsyndromic orofacial clefts (OFCs) are complex traits characterized by multifactorial inheritance and wide phenotypic variability. Numerous studies have shown subtle differences in the faces of unaffected relatives from cleft families compared to controls, the implication being that such outward differences are an incomplete expression reflecting an underlying genetic predisposition. Twins discordant for OFCs provide a unique opportunity to further test this idea, as the unaffected co-twin shares on average 50% (for dizygotic twins) and 100% (for monozygotic twins) of the genetic risk factors as the affected twin. We used 3D surface imaging and spatially-dense morphometry to compare facial shape in a sample of 44 unaffected co-twins and age- and sex-matched unaffected controls (n = 241). Unaffected co-twins showed statistically significant differences in the midface, lateral upper face, and forehead regions, compared to controls. Furthermore, co-twins were characterized by a distinct pattern of midfacial retrusion, broader upper faces, and greater protrusion of the mandible and brow ridges. This same general facial pattern was shown in both unaffected monozygotic and dizygotic co-twin subsets. These results provide additional support that altered facial shape is a phenotypic marker for OFC susceptibility.
非综合征性口面部裂隙（OFCs）是具有多因素遗传和广泛表型变异性的复杂性状。大量研究表明，与对照组相比，来自腭裂家庭的未受影响亲属的面部存在细微差异，这意味着这种外在差异是反映潜在遗传易感性的不完全表现。患OFCs的双卵双胞胎为进一步验证这一观点提供了独特的机会，因为未受影响的同卵双胞胎与受影响的双胞胎平均共享50%（双卵双胞胎）和100%（同卵双胞胎）的遗传风险因素。我们使用3D表面成像和空间密集形态测量法，对44名未受影响的同卵双胞胎以及年龄和性别匹配的未受影响对照组（n = 241）的面部形状进行了比较。与对照组相比，未受影响的同卵双胞胎在中面部、外侧上脸和额头区域表现出统计学上的显著差异。此外，同卵双胞胎的特征是中面部后缩、上脸更宽、下颌骨和眉脊突出更明显。这种相同的一般面部模式在未受影响的同卵和双卵双胞胎亚组中均有体现。这些结果进一步支持了面部形状改变是OFC易感性的表型标志物这一观点。
