目标-Angelman综合征(AS)是一种罕见的,遗传,以严重言语障碍为特征的神经发育障碍,认知和运动技能伴随着独特的行为,面部特征明显,癫痫和睡眠问题患病率高。尽管有一些AS患者身材矮小的报道,该特征不包括在2005年定义的临床标准中.我们调查了AS患者中突变类型的生长模式,生长期,家族史和内分泌异常。方法-数据来自AS国家诊所的患者医疗档案。突变亚型分为缺失和非缺失。定义了四个生长期:学龄前,童年,峰高速度,和最终高度。结果-该队列包括88名个体(46名男性),54(61.4%)携带缺失亚型。每个人的中位数为3个观察值,产生280个数据点。与普通人群相比,最终身高-SDS显着降低(-1.23±1.26,p<0.001),和在删除组vs.非缺失(-1.67±1.3vs.-0.65±0.96,p=0.03)。与学龄前的身高SDS相比,最终身高SDS显着降低(-1.32vs-0.47,p=0.007)。患者的最终身高-SDS显着低于父母'(Δ最终身高-SDS=0.94±0.99,p=0.002)。与一般人群相比,IGF1-SDS显着降低(-0.55±1.61,p=0.04),在缺失组中具有较低的值(-0.70±1.44,p=0.01)结论-AS患者在儿童期和青春期表现出特定的生长模式,与正常人群相比,其最终身高显着下降,甚至更低的删除子组中,这可能归因于IGF1水平降低。我们建议在临床标准中增加身材矮小,并为AS人群制定调整后的生长曲线。
BACKGROUND: Angelman syndrome (AS) is a rare, genetic, neurodevelopmental disorder characterized by severe impairments in speech, cognition, and motor skills accompanied by unique behaviors, distinct facial features, and high prevalence of epilepsy and sleep problems. Despite some reports of short stature among AS patients, this feature is not included in the clinical criteria defined in 2005. We investigated growth patterns among AS patients with respect to mutation type, growth periods, family history, and endocrine abnormalities.
METHODS: Data were collected from patients\' medical files in AS National Clinic. Mutation subtypes were divided to deletion and non-deletion. Four growth periods were defined: preschool, childhood, peak height velocity, and final height.
RESULTS: The cohort included 88 individuals (46 males), with 54 (61.4%) carrying deletion subtype. A median of 3 observations per individual produced 280 data points. Final height SDS was significantly lower compared to general population (-1.23 ± 1.26, p < 0.001), and in deletion group versus non-deletion (-1.67 ± 1.3 vs. -0.65 ± 0.96, p = 0.03). Final height SDS was significantly lower compared to height SDS in preschool period (-1.32 vs. -0.47, p = 0.007). Patient\'s final height SDS was significantly lower than the parents\' (∆final-height SDS = 0.94 ± 0.99, p = 0.002). IGF1-SDS was significantly decreased compared to general population (-0.55 ± 1.61, p = 0.04), with lower values among deletion group (-0.70 ± 1.44, p = 0.01).
CONCLUSIONS: AS patients demonstrate specific growth pattern with deceleration during childhood and adolescence, resulting in significantly decreased final height compared to normal population, and even lower among deletion subgroup, which could be attributed to reduced IGF1 levels. We propose adding short stature to the clinical criteria and developing adjusted growth curves for AS population.