Stevenson Roger E, Brasington Cam K, Skinner Cindy, Simensen Richard J, Spence J Edward, Kesler Shelli, Reiss Allan L, Schwartz Charles E
Greenwood Genetic Center, J.C. Self Research Institute of Human Genetics, Greenwood, South Carolina 29646, USA.
Am J Med Genet A. 2007 Oct 1;143A(19):2321-9. doi: 10.1002/ajmg.a.31928.
A syndrome with multisystem manifestations has been observed in three generations of a Caucasian family. The findings in seven females provide a composite clinical picture of microcephaly, short stature, small retroverted ears, full tip of the nose overhanging the columella, short philtrum, thin upper lip, soft tissue excrescences at the angle of the mouth, small mandible, small hands and feet with brachydactyly, finger V clinodactyly, flat feet, an excessive number of fingerprint arches, and mild impairment of cognitive function. Two males were more severely affected and died in the initial months of life. They showed intrauterine growth retardation, broad cranium with wide sutures and fontanelles, cardiac defects, small hands and feet with abnormal digital creases and small nails, and genital abnormalities. The affected males had low serum calcium in the neonatal period. Serum calcium, phosphorous, and parathormone levels in the females were normal. Radiographs showed cortical thickening of the long bones, underdevelopment of the frontal sinuses, narrow pelvis and hypoplasia of the middle phalanx of finger five. MRI of the brain showed slightly reduced brain volumes and an extra gyrus of the superior temporal region. X-inactivation studies showed near complete skewing in two affected females, but were not informative in three others. X-linkage as the mode of inheritance is proposed on the basis of different severity in males/females, complete skewing of X-inactivation in informative females, and a lod score (1.5) suggestive of linkage to markers in Xq26-q27.
在一个高加索家庭的三代人中观察到一种具有多系统表现的综合征。对7名女性的检查结果呈现出小头畸形、身材矮小、小耳向后倾、鼻尖丰满悬于鼻小柱上方、人中短、上唇薄、口角软组织赘生物、小下颌、短指（趾）畸形的小手和小脚、第5指尺侧弯曲、扁平足、指纹弓数量过多以及轻度认知功能障碍的综合临床表现。两名男性受影响更严重，在出生后的最初几个月死亡。他们表现出宫内生长迟缓、颅骨宽且缝和囟门宽、心脏缺陷、有异常指（趾）褶痕和小指甲的小手和小脚以及生殖器异常。患病男性在新生儿期血清钙水平较低。女性的血清钙、磷和甲状旁腺激素水平正常。X线片显示长骨皮质增厚、额窦发育不全、骨盆狭窄和第5指中节指骨发育不全。脑部MRI显示脑容量略有减少以及颞上区有一个额外的脑回。X染色体失活研究显示两名受影响女性的X染色体失活几乎完全偏斜，但另外三名女性的研究结果无信息价值。基于男性/女性的不同严重程度、信息性女性中X染色体失活的完全偏斜以及提示与Xq26 - q27中的标记连锁的对数优势分数（1.5），提出X连锁作为遗传方式。
