Baroncini Anna, Castelluccio Pia, Morleo Manuela, Soli Fiorenza, Franco Brunella
Unit of Medical Genetics, ASL, Imola, Italy.
Am J Med Genet A. 2007 Jan 1;143A(1):51-7. doi: 10.1002/ajmg.a.31557.
Terminal osseous dysplasia with pigmentary defects is an extremely rare condition characterized by the triad of pigmentary anomalies of the skin, skeletal abnormalities of the limbs and recurring digital fibromatosis of childhood, with considerable interfamilial and intrafamilial variability of expression. It has recently been added to the small group of X-linked dominant disorder with prenatal male lethality on the basis of a four-generation pedigree in which only females were affected, male progeny was decreased and the number of spontaneous abortions was increased. In this clinical report, we describe a 2-year-old girl with full expression of the syndrome including skin defects, skeletal anomalies and recurrent fibromatosis of fingers and toes and her mother who presents with only multiple hypertrophic oral frenula. As previously demonstrated, our patients also show an extremely skewed X-inactivation on blood cells, strongly suggesting that there is selective disadvantage for cells carrying the mutated gene on their active X chromosome. Terminal osseous dysplasia with pigmentary defects could represent an additional example of extreme intrafamilial variability as already described for other X-linked dominant disorders.
伴有色素沉着缺陷的末端骨发育异常是一种极其罕见的病症,其特征为皮肤色素异常、肢体骨骼异常以及儿童复发性指(趾)纤维瘤病三联征,在家族间和家族内表达存在相当大的差异。基于一个四代家系,其中仅女性患病,男性后代减少且自然流产数量增加,最近它被归入伴有产前男性致死性的X连锁显性疾病这一小组。在本临床报告中,我们描述了一名2岁女童,其综合征表现完全,包括皮肤缺陷、骨骼异常以及手指和脚趾的复发性纤维瘤病,还有她的母亲,其仅表现为多个肥厚性口腔系带。如先前所示,我们的患者血细胞中还显示出极其偏态的X染色体失活,强烈提示携带突变基因的细胞在其活性X染色体上存在选择性劣势。伴有色素沉着缺陷的末端骨发育异常可能是家族内极端变异性的又一实例,正如其他X连锁显性疾病所描述的那样。