Rosenbloom A L, Guevara Aguirre J, Rosenfeld R G, Fielder P J
University of Florida, Gainesville.
N Engl J Med. 1990 Nov 15;323(20):1367-74. doi: 10.1056/NEJM199011153232002.
Laron-type dwarfism, which is characterized by the clinical appearance of isolated growth hormone deficiency with elevated serum levels of growth hormone and decreased serum levels of insulin-like growth factor I (IGF-I), has been described in approximately 50 patients. This condition is caused by a deficiency of the cellular receptor for growth hormone, and it is transmitted as an autosomal recessive trait, as indicated by an equal sex distribution and a high rate of consanguinity in affected families. We studied 20 patients (19 females and 1 male, 2 to 49 years of age), from an inbred Spanish population in southern Ecuador, who had the clinical features of Laron-type dwarfism.
Seventeen patients were members of two large pedigrees. Among the 13 affected sibships, there were 19 affected and 24 unaffected female siblings and 1 affected and 21 unaffected male siblings. The patients' heights ranged from 10.0 to 6.7 SD below the normal mean height for age in the United States. In addition to the previously described features, 15 patients had limited elbow extensibility, all had blue scleras, affected adults had relatively short extremities, and all four affected women over 30 years of age had hip degeneration. Basal serum concentrations of growth hormone were elevated in all affected children (30 to 160 micrograms per liter) and normal to moderately elevated in the adults. The serum level of growth hormone-binding protein ranged from 1 to 30 percent of normal; IGF-I concentrations were low--less than or equal to 7 micrograms per liter in the children and less than or equal to 66 micrograms per liter in the adults (normal for Ecuadorean women, 98 to 238). Serum levels of IGF-II and growth hormone-dependent IGF-binding protein-3 were also low.
We describe an inbred population with a high incidence of growth hormone-receptor deficiency resulting in a clinical picture resembling Laron-type dwarfism but differing principally in showing a marked predominance of affected females. This population, of Mediterranean origin, may be genetically related to other reported populations with Laron-type dwarfism, but with the genetic defect linked to a trait resulting in the early fetal death of most affected males.
拉伦型侏儒症的特征是临床上表现为孤立性生长激素缺乏，血清生长激素水平升高而胰岛素样生长因子I（IGF-I）血清水平降低，已报道约50例患者。这种情况是由生长激素的细胞受体缺乏引起的，呈常染色体隐性遗传，这一点在受累家庭中两性分布均等及近亲结婚率高得到体现。我们研究了来自厄瓜多尔南部一个近亲通婚的西班牙人群中的20例患者（19名女性和1名男性，年龄2至49岁），他们具有拉伦型侏儒症的临床特征。
17例患者属于两个大家系。在13个受累同胞组中，有19名受累和24名未受累的女性同胞以及1名受累和21名未受累的男性同胞。患者的身高比美国同年龄正常平均身高低10.0至6.7个标准差。除了先前描述的特征外，15例患者肘部伸展受限，所有患者巩膜呈蓝色，成年患者四肢相对较短，所有4名30岁以上的受累女性有髋部退变。所有受累儿童的基础血清生长激素浓度升高（30至160微克/升），成年患者正常至中度升高。生长激素结合蛋白的血清水平为正常的1%至30%；IGF-I浓度较低——儿童低于或等于7微克/升，成年患者低于或等于66微克/升（厄瓜多尔女性正常范围为98至238）。IGF-II和生长激素依赖性IGF结合蛋白-3的血清水平也较低。
我们描述了一个近亲通婚人群，其中生长激素受体缺乏的发生率很高，导致临床表现类似于拉伦型侏儒症，但主要不同之处在于受累女性明显占优势。这个起源于地中海地区的人群可能在基因上与其他报道的拉伦型侏儒症人群有关，但基因缺陷与导致大多数受累男性早期胎儿死亡的一个性状相关。
