Nishimura Gen, Hasegawa Tomonobu, Kinoshita Eiichi, Tanaka Yoko, Kurosawa Kenzi, Yoshimoto Masaaki
Japanese Skeletal Dysplasia Consortium, Tokyo, Japan.
Am J Med Genet A. 2004 Jul 15;128A(2):204-8. doi: 10.1002/ajmg.a.30030.
We report on a previously undescribed syndrome characterized by generalized skeletal alterations and overgrowth in three unrelated individuals: a boy who died at age 16 years, a 16-year-old girl, and a 15-month-old boy. The skeletal changes included bony overgrowth of the skull base, spondylar dysplasia, and undermodeling of the tubular bones. Bone age was accelerated in early childhood. Overgrowth, which was independent of GH-IGF axis, was of prenatal onset in the two boys, but postnatal in the girl. In the two adolescents, growth rate did not decline with age, and high-dose estrogen therapy failed to induce physeal fusion. Their adolescent height reached +4 approximately +7 SD of the mean. Delayed puberty in the girl and cryptorchidism and hypospadias in the younger boy raised the possibility that hypogonadism is a syndromic constituent. Molecular analysis of IGF2, GPC3, and FGFR3 in the older boy yielded no abnormalities.
我们报告了一种先前未描述的综合征，其特征为三名无血缘关系个体出现全身性骨骼改变和过度生长：一名16岁死亡的男孩、一名16岁女孩和一名15个月大的男孩。骨骼变化包括颅底骨质过度生长、脊椎发育异常以及管状骨塑形不足。儿童早期骨龄加速。过度生长与生长激素-胰岛素样生长因子轴无关，在两名男孩中为产前发病，而在女孩中为产后发病。在两名青少年中，生长速率并不随年龄下降，高剂量雌激素治疗未能诱导骨骺融合。他们的青少年身高达到平均身高的约+4至+7标准差。女孩青春期延迟，年幼男孩隐睾和尿道下裂，提示性腺功能减退可能是该综合征的组成部分。对年长男孩的胰岛素样生长因子2（IGF2）、磷脂酰肌醇蛋白聚糖3（GPC3）和成纤维细胞生长因子受体3（FGFR3）进行分子分析未发现异常。
