与 SHOX 缺陷相比，SHOX 增强子缺失的患者对 GH 治疗的生长反应更大。

The growth response to GH treatment is greater in patients with SHOX enhancer deletions compared to SHOX defects.

机构信息

Departments of PediatricsClinical GeneticsLeiden University Medical Center, PO Box 9600, 2300 RC Leiden, The NetherlandsDutch Growth Research Foundation ('Stichting Kind en Groei')PO Box 23068, 3001 KB Rotterdam, The NetherlandsDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The NetherlandsDepartment of Clinical GeneticsVU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The NetherlandsDepartment of Clinical GeneticsErasmus Medical Center, PO Box 2060, 3000 CB Rotterdam, The Netherlands.

出版信息

Eur J Endocrinol. 2015 Nov;173(5):611-21. doi: 10.1530/EJE-15-0451. Epub 2015 Aug 11.

DOI:10.1530/EJE-15-0451

PMID:26264720

Abstract

OBJECTIVE

Short stature caused by point mutations or deletions of the short stature homeobox (SHOX) gene (SHOX haploinsufficiency (SHI)) is a registered indication for GH treatment. Patients with a SHOX enhancer deletion (SED) have a similar phenotype, but their response to GH is unknown. It is uncertain if duplications of SHOX or its enhancer (SDUP) cause short stature. This study aimed to describe the clinical characteristics and growth response to GH treatment in patients with aberrations of SHOX and its enhancers.

DESIGN

In this retrospective multi-center study (2002-March 2014) clinical information was available from 130 patients (72 SHI, 44 SED, and 14 SDUP) of whom 52 patients were treated with GH. We evaluated height, sitting height (SH), arm span, dysmorphic features and indicators of the growth response to GH (delta height SDS, height velocity, and index of responsiveness).

RESULTS

Patients with SEDs showed similar HtSDS to patients with SHI (-2.3 and -2.6, respectively, P=0.2), but they were less disproportionate (SH/height ratio SDS 2.0 vs 3.1 (P<0.01) and extremities/trunk ratio 2.57 vs 2.43 (P=0.03)). The 1st year growth response to GH treatment was significantly greater in prepubertal patients with SEDs than SHI. None of the patients with an SDUP was disproportionate and SDUP cosegregated poorly with short stature; their growth response to GH treatment (n=3) was similar to the other groups.

CONCLUSIONS

Patients with SEDs are equally short, but less disproportionate than patients with SHI, and show a greater response to GH.

摘要

目的

由短身材同源盒（SHOX）基因的点突变或缺失引起的身材矮小（SHOX 基因单倍剂量不足（SHI））是 GH 治疗的适应证。具有 SHOX 增强子缺失（SED）的患者具有相似的表型，但他们对 GH 的反应尚不清楚。SHOX 或其增强子（SDUP）的重复是否导致身材矮小尚不确定。本研究旨在描述 SHOX 及其增强子异常患者的临床特征和对 GH 治疗的生长反应。

设计

在这项回顾性多中心研究中（2002 年至 2014 年 3 月），可从 130 名患者（72 名 SHI、44 名 SED 和 14 名 SDUP）中获得临床信息，其中 52 名患者接受了 GH 治疗。我们评估了身高、坐高（SH）、臂展、畸形特征以及 GH 治疗的生长反应指标（身高 SDS 变化、身高速度和反应指数）。

结果

SED 患者的 HtSDS 与 SHI 患者相似（分别为-2.3 和-2.6，P=0.2），但他们的不成比例程度较低（SH/身高比 SDS 为 2.0 比 3.1（P<0.01）和四肢/躯干比为 2.57 比 2.43（P=0.03））。SED 患者在青春期前的第一年对 GH 治疗的生长反应明显大于 SHI 患者。没有一个 SDUP 患者不成比例，SDUP 与身材矮小的相关性较差；他们对 GH 治疗的反应（n=3）与其他组相似。