孤立性SHOX基因单倍剂量不足所致身材矮小：诊断与治疗的最新进展

Short stature caused by isolated SHOX gene haploinsufficiency: update on the diagnosis and treatment.

作者信息

Jorge Alexander A L, Funari Mariana Fa, Nishi Mirian Y, Mendonca Berenice B

机构信息

Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, SP, Brazil.

出版信息

Pediatr Endocrinol Rev. 2010 Dec;8(2):79-85.

PMID:21150837

Abstract

Heterozygous SHOX defects are observed in about 50 to 90% of patients with Leri-Weill dyschondrosteosis (LWD), a common dominant inherited skeletal dysplasia; and in 2 to 15% of children with idiopathic short stature (ISS), indicating that SHOX defects are the most important monogenetic cause of short stature. In addition, children selected by disproportionate idiopathic short stature had a higher frequency of SHOX mutations (22%). A careful clinical evaluation of family members with short stature is recommended since it usually revealed LWD patients in families first classified as having ISS or familial short stature. SHOX-molecular analysis is indicated in families with LWD and ISS children with disproportionate short stature. Treatment with recombinant human growth hormone is considered an accepted approach to treat short stature associated with isolated SHOX defect. Here we review clinical, molecular and therapeutic aspects of SHOX haploinsufficiency.

摘要

在约50%至90%的Léri-Weill软骨发育不全（LWD）患者中观察到杂合子SHOX缺陷，LWD是一种常见的显性遗传性骨骼发育不良；在2%至15%的特发性矮小症（ISS）儿童中也有发现，这表明SHOX缺陷是身材矮小最重要的单基因病因。此外，因不成比例的特发性矮小症而入选的儿童中SHOX突变频率更高（22%）。建议对身材矮小的家庭成员进行仔细的临床评估，因为这通常会在最初被归类为患有ISS或家族性矮小症的家庭中发现LWD患者。对于有LWD以及身材不成比例矮小的ISS儿童的家庭，建议进行SHOX分子分析。使用重组人生长激素治疗被认为是治疗与孤立性SHOX缺陷相关的身材矮小的一种公认方法。在此，我们综述SHOX单倍剂量不足的临床、分子和治疗方面。