Sandberg Elizabeth S, Calikoglu Ali S, Loechner Karen J, Snyder Lydia L
Division of Endocrinology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Division of Pediatric Endocrinology, Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta, GA, USA.
Case Rep Endocrinol. 2017;2017:7287351. doi: 10.1155/2017/7287351. Epub 2017 Aug 30.
Deficiency of the short stature homeobox-containing (SHOX) gene is a frequent cause of short stature in children (2-15%). Here, we report 7 siblings with SHOX deficiency due to a point mutation in the SHOX gene. Index case was a 3-year-old male who presented for evaluation of short stature. His past medical history and birth history were unremarkable. Family history was notable for multiple individuals with short stature. Physical exam revealed short stature, with height standard deviation score (SDS) of -2.98, as well as arm span 3 cm less than his height. His laboratory workup was noncontributory for common etiologies of short stature. Due to significant familial short stature and shortened arm span, SHOX gene analysis was performed and revealed patient is heterozygous for a novel SHOX gene mutation at nucleotide position c.582. This mutation is predicted to cause termination of the SHOX protein at codon 194, effectively causing haploinsufficiency. Six out of nine other siblings were later found to also be heterozygous for the same mutation. Growth hormone was initiated in all seven siblings upon diagnosis and they have demonstrated improved height SDS.
含矮小同源框（SHOX）基因缺陷是儿童身材矮小的常见原因（占2%-15%）。在此，我们报告7名因SHOX基因突变导致SHOX基因缺陷的兄弟姐妹。索引病例是一名3岁男性，因身材矮小前来评估。他既往病史和出生史无异常。家族史中多个个体身材矮小。体格检查显示身材矮小，身高标准差评分（SDS）为-2.98，且臂展比身高短3厘米。他的实验室检查对身材矮小的常见病因无诊断意义。由于显著的家族性身材矮小和缩短的臂展，进行了SHOX基因分析，结果显示患者在核苷酸位置c.582处存在一种新的SHOX基因突变的杂合子。该突变预计会导致SHOX蛋白在第194密码子处终止，从而有效导致单倍剂量不足。后来发现其他9名兄弟姐妹中有6名也为同一突变的杂合子。所有7名兄弟姐妹在诊断后均开始使用生长激素，他们的身高SDS已有所改善。
