Gucev Zoran, Tasic Velibor, Plaseska-Karanfilska Dijana, Konstantinova Marina Krstevska, Stamatova Ana, Dimishkovska Marija, Laban Nevenka, Polenakovic Momir
Pediatr Endocrinol Rev. 2016 Jun;13(4):749-55.
LHX4 mutations are rare in combined pituitary hormone deficiency, and even rarer in isolated GHD. We describe a 14 years old boy who was referred for investigation of short stature. Convergent strabismus, nystagmus was present. At the age of 5 years his gait was unstable. A progressive myopathy ensued. Tests of pituitary reserve showed partial IGHD (8.2 ng/ml). Other pituitary hormones were within normal range. Muscle biopsy showed congenital myopathy of undefined etiology. MRI of the brain revealed the empty sella syndrome. Targeted resequencing with a panel containing probe sets for enrichment and analysis of > 4,800 clinically relevant genes, targeting 12Mb of the human genome revealed the c.250C>T (R84C) LHX4 mutation. His father is healthy, with no myopathy or pituitary deficiencies, but has the same LHX4 mutation. This report extends the range of phenotypes associated with LHX4 gene mutations. To the best of our knowledge, we are the first to report on congenital myopathy in an LHX4 gene mutation. Forthwith, we offer a comprehensive review of the patients published so far with their clinical and genetic characteristics.
LHX4突变在联合垂体激素缺乏症中较为罕见，在孤立性生长激素缺乏症中更为罕见。我们描述了一名14岁因身材矮小前来检查的男孩。他存在会聚性斜视、眼球震颤。5岁时步态不稳，随后出现进行性肌病。垂体储备功能测试显示部分性孤立性生长激素缺乏（8.2 ng/ml），其他垂体激素在正常范围内。肌肉活检显示为病因不明的先天性肌病。脑部MRI显示为空蝶鞍综合征。使用包含用于富集和分析>4800个临床相关基因的探针集的panel进行靶向重测序，靶向人类基因组的12Mb区域，发现了c.250C>T（R84C）LHX4突变。他的父亲健康，没有肌病或垂体功能缺陷，但有相同的LHX4突变。本报告扩展了与LHX4基因突变相关的表型范围。据我们所知，我们是首个报道LHX4基因突变导致先天性肌病的。随即，我们对迄今为止已发表的具有临床和遗传特征的患者进行了全面综述。
