Craniofacial Dysmorphology Associated with Phelan-McDermid Syndrome using Three-Dimensional Morphometrics

本研究旨在描述与费兰-麦克德米德综合征相关的颅面畸形的特征。 经前综合征(OMIM#606232)，这是一种遗传性疾病，已在1,500多人中诊断出。这个 与经前综合征相关的颅面畸形尚未得到很好的证实。这些文献报道了各种各样的东西 特征包括鼻球状，耳朵畸形，丰满的嘴唇，内皮褶，巨头畸形， 小头，高弓上颚，丰满的脸颊，眼轮周围丰满，尖尖的下巴，宽阔的鼻梁，较长的鼻孔， 颧骨发育不全，小头畸形，眼睛深陷，面中部扁平。我们的研究将包括一名体型较大的患者 这将提供对这些变形特征在频率和强度上的变化的理解 与经前综合症有关。这项研究将使用几何形态测量方法来允许变化 更准确地定义和可视化，从而对“球茎鼻”有更具体和普遍的理解， 例如，将会出现。这项研究将提供更精确和系统的表型研究。 与经前综合症相关的，重点是面部畸形，然后以前已经完成。该项目 将通过临床医生之间的跨学科协作来优化可用的协同效应， 发育生物学家和解剖学家因此促进了对经前综合征颅骨畸形的理解 如果这些科学家孤立地工作，会产生什么后果。这一研究模式将利用 经前综合征的临床专业知识，量化畸形的解剖学，以及发育生物学 探索用于描述经前综合症的发育模型。临床遗传学家对经前综合症的初步诊断是 通常基于在患者身上观察到的物理特征的特征模式。以提供量化的 评估与经前综合征相关的颅面畸形，几何形态测量方法将 提供对与综合征相关的平均形态的更深入的了解以及对 与年龄、性别和血统差异有关的变异。畸形可以用以下方法进行评估 放置在三维坐标系内并通过密集表面模型的解剖地标 头面部复合体。本研究将从以下几个方面促进经前综合征的诊断和治疗：(1) 准确描述与经前综合征相关的颅面畸形；(2)确定变异 在患者群体中与经前综合症相关；(3)量化性别和血统与 在经前综合征中观察到的形态异常；以及(4)定义与经前综合征相关的对生长的影响。 头面部复合体和头面部区域。

This research seeks to characterize the craniofacial dysmorphology associated with Phelan-McDermid syndrome (PMS) (OMIM #606232), a genetic disorder that has been diagnosed in over 1500 individuals. The craniofacial dysmorphology associated with PMS has not been well established. The literature reports a variety of characteristics, including bulbous nose, ear anomalies, full lips, epicanthal folds, macrocephaly, dolicocephaly, high arch palate, full cheeks, periorbitial fullness, pointed chin, wide nasal bridge, long pholtrum, malar hypoplasia, microcephaly, deep set eyes, and flat midface. Our study will include a larger patient population that will provide an understanding of how these dysmorphic features vary in frequency and intensity associated with PMS. The research will use geometric morphometric approaches to allow the variation to be more precisely defined and visualized, so that a more specific and universal understanding of “bulbous nose”, for instance, will emerge. This research will provide a more precise and systematic study of the phenotype associated with PMS with a focus on the facial dysmorphology then has been completed before. The project will optimize the synergies available through cross-disciplinary collaborations between clinicians, developmental biologists, and anatomists thus advancing understanding of PMS cranial dysmorphology beyond what would result if these scientists were working in isolation. The research model will capitalize on clinical expertise of PMS, anatomical science to quantify the dysmorphology, and developmental biology to explore developmental models for characterizing PMS. The initial diagnosis of PMS by clinical geneticists is often based on a characteristic pattern of physical features observed in a patient. To provide a quantitative assessment of the craniofacial dysmorphology associated with PMS, geometric morphometric approaches will provide greater insights into the mean morphology associated with the syndrome along with an evaluation of the variation associated with age, sex, and ancestry differences. Dysmorphology can be evaluated using anatomical landmarks placed within a three-dimensional coordinate system and through dense surface models of the craniofacial complex. This study will advance diagnosis and treatment of PMS in the following ways: (1) Precisely characterize craniofacial dysmorphologies associated with PMS; (2) determine the variation associated by PMS in the patient population; (3) quantify the effects of sex and ancestry associated with the dysmorphologies observed in PMS; and (4) define the impact on growth associated with PMS in the craniofacial complex and within craniofacial regions.