Connor Cody J, Shchelochkov Oleg A, Ciliberto Heather
Carver College of Medicine, University of Iowa Hospitals and Clinics.
Stead Family Department of Pediatrics, University of Iowa Hospitals and Clinics.
Am J Med Genet A. 2015 Oct;167A(10):2459-62. doi: 10.1002/ajmg.a.37176. Epub 2015 Jun 8.
Terminal osseous dysplasia with pigmentary defects (TODPD) is a rare, X-linked syndrome classically characterized by distal limb anomalies, pigmented skin defects of the face, and recurrent digital fibromas. X-inactivation plays a major role in determining the range of phenotypic expression. Thus, patients can demonstrate a wide spectrum of disease severity, making accurate diagnosis more challenging. Recent studies have identified a FLNA c.5217G>A mutation as the cause of TODPD, allowing for diagnostic genetic testing. We present a case of molecularly confirmed TODPD in a girl with the 47,XXX chromosomal complement and deformities of the hands and feet, craniofacial abnormalities, and discolored, linear facial lesions. Skin biopsy of the patient's facial lesion revealed absent papillary dermal elastic fibers, consistent with anetoderma, which contrasts with the dermal hypoplasia described in the only other such facial biopsy reported in the literature. The finding of absent elastic fibers in the skin lesions suggests that mutated filamin A, in part, exerts its effects through dysregulated elastin biology, which may explain the nature of many connective tissue pleotropic effects in FLNA-related disorders.
伴有色素沉着缺陷的终末骨发育异常(TODPD)是一种罕见的X连锁综合征,典型特征为肢体远端异常、面部色素沉着性皮肤缺陷和复发性指纤维瘤。X染色体失活在决定表型表达范围方面起主要作用。因此,患者可表现出广泛的疾病严重程度,这使得准确诊断更具挑战性。最近的研究已确定FLNA基因c.5217G>A突变是TODPD的病因,从而可进行诊断性基因检测。我们报告一例分子确诊的TODPD病例,患者为一名47,XXX染色体核型的女孩,有手足畸形、颅面异常以及面部线状变色皮损。对患者面部皮损进行皮肤活检,结果显示乳头层真皮弹性纤维缺失,符合皮肤弹力纤维缺失症,这与文献中报道的另一例此类面部活检所描述的真皮发育不全不同。皮肤病变中弹性纤维缺失的发现表明,突变的细丝蛋白A部分通过弹性蛋白生物学失调发挥作用,这可能解释了FLNA相关疾病中许多结缔组织多效性效应的本质。