Grunauer Michelle, Jorge Alexander A L
Pediatric Intensive Care Unit, Hospital de los Valles, Escuela de Medicina, Universidad San Francisco de Quito (USFQ), Quito, Ecuador.
Unidade de Endocrinologia Genetica (LIM25), Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil.
Growth Horm IGF Res. 2018 Feb;38:29-33. doi: 10.1016/j.ghir.2017.12.003. Epub 2017 Dec 6.
Adult height and growth patterns are largely genetically programmed. Studies in twins have indicated that the heritability of height is high (>80%), suggesting that genetic variation is the main determinant of stature. Height exhibits a normal (Gaussian) distribution according to sex, age, and ancestry. Short stature is usually defined as a height which is 2 standard deviations (S.D.) less than the mean height of a specific population. This definition includes 2.3% of the population and usually includes healthy individuals. In this group of short stature non-syndromic conditions, the genetic influence occurs polygenically or oligogenically. As a rule, each common genetic variant accounts for a small effect (1mm) on individual height variation. Recently, several studies demonstrated that some rare variants can cause greater effect on height, without causing a syndromic condition. In more extreme cases, height SDS below 2.5 or 3 (which would comprise approximately 0.6 and 0.1% of the population, respectively) is frequently associated with syndromic conditions and are usually caused by a monogenic defect. More than 1,000 inherited/genetic diseases have growth disorder as an important phenotype. These conditions are usually responsible for syndromic short stature. In the coming years, we expect to discover several genetic causes of short stature, thereby explaining the phenotype of what we currently classify as short stature of unknown cause. These discoveries will have a profound impact on the follow-up and treatment of these children.
成人身高和生长模式在很大程度上由基因编程决定。对双胞胎的研究表明,身高的遗传度很高(>80%),这表明基因变异是身高的主要决定因素。根据性别、年龄和血统,身高呈现正态(高斯)分布。身材矮小通常定义为比特定人群平均身高低2个标准差(S.D.)的身高。这个定义涵盖了2.3%的人群,通常包括健康个体。在这组非综合征性身材矮小的情况中,遗传影响以多基因或寡基因的方式发生。通常,每个常见的基因变异对个体身高变异的影响较小(1毫米)。最近,几项研究表明,一些罕见变异可对身高产生更大影响,且不会导致综合征。在更极端的情况下,身高标准差评分低于2.5或3(分别约占人群的0.6%和0.1%)通常与综合征情况相关,且通常由单基因缺陷引起。超过1000种遗传性/基因性疾病将生长障碍作为重要表型。这些情况通常是综合征性身材矮小的原因。在未来几年,我们预计会发现身材矮小的几种遗传原因,从而解释我们目前归类为不明原因身材矮小的表型。这些发现将对这些儿童的随访和治疗产生深远影响。