Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
Am J Med Genet A. 2013 Mar;161A(3):518-26. doi: 10.1002/ajmg.a.35772. Epub 2013 Feb 7.
It is debatable whether Hajdu-Cheney syndrome (HCS) and serpentine fibula-polycystic kidney syndrome (SFPKS) represent a single clinical entity with a variable degree of expression or two different entities, because both disorders share common clinical and radiological manifestations, including similar craniofacial characteristics, and defective bone mineralization. Since it was shown that heterozygous truncating mutations in NOTCH2 are responsible for both HCS and SFPKS, 37 patients with HCS and four patients with SFPKS are reported. To elucidate the clinical consequences of NOTCH2 mutations, we present detailed clinical information for seven patients with truncating mutations in exon 34 of NOTCH2, six with HCS and one with SFPKS. In addition, we review all the reported patients whose clinical manifestations are available. We found 13 manifestations including craniofacial features, acroosteolysis, Wormian bones, and osteoporosis in >75% of NOTCH2-positive patients. Acroosteolysis was observed in two patients with SFPKS and bowing fibulae were found in two patients with HCS. These clinical and molecular data would support the notion that HCS and SFPKS are a single disorder.
哈吉杜-切尼综合征（HCS）和蛇形腓骨-多囊肾病综合征（SFPKS）是否代表一种具有不同表达程度的单一临床实体，或者是两种不同的实体，这是有争议的，因为这两种疾病具有共同的临床和放射学表现，包括相似的颅面特征和骨矿物质化缺陷。由于已经表明 NOTCH2 中的杂合截断突变是 HCS 和 SFPKS 的共同致病原因，因此报告了 37 例 HCS 患者和 4 例 SFPKS 患者。为了阐明 NOTCH2 突变的临床后果，我们报告了 7 例 NOTCH2 外显子 34 截断突变的患者的详细临床信息，其中 6 例为 HCS，1 例为 SFPKS。此外，我们回顾了所有有临床表现的报道患者。我们发现 13 种表现，包括颅面特征、肢端骨溶解、脑回骨和骨质疏松症，在>75%的 NOTCH2 阳性患者中出现。在 2 例 SFPKS 患者中观察到肢端骨溶解，在 2 例 HCS 患者中发现弯曲的腓骨。这些临床和分子数据将支持 HCS 和 SFPKS 是一种单一疾病的观点。
