Growth without Growth Hormone and Similar Dysmorphic Features in Three Patients with Sporadic Combined Pituitary Hormone Deficiencies
Growth without Growth Hormone and Similar Dysmorphic Features in Three Patients with Sporadic Combined Pituitary Hormone Deficiencies
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DOI：
10.1159/000245932
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发表时间：
2009-01-01
期刊：
影响因子：
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通讯作者：
Phillip, M.
中科院分区：
文献类型：
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作者：
Gat-Yablonski, G.;Lazar, L.;Phillip, M.
背景/目的：HESX1基因突变与多种表型有关：隔视神经发育不良、中线缺陷、继发性垂体功能减退症、孤立性生长激素(GH)缺乏症或复合性垂体激素缺乏症(CPHD)。这项研究检测了慢性阻塞性肺病患者中HESX1基因突变的发生率。患者/方法：对60例散发性CPHD患者进行HESX1基因突变筛查。结果：发现3例HESX1基因Asn125Ser杂合子。3例均表现为新生儿期全垂体功能低下，2例表现为严重低血糖和新生儿黄疸，1例表现为呼吸窘迫。体格检查明显表现为面部粗糙，耳朵突出、大、低，骨骼异常。2例患者行磁共振成像检查，发现垂体前叶和后叶发育不良，无其他中线异常。尽管持续的生长激素缺乏和胰岛素样生长因子1水平检测不到，但所有患者在没有生长激素治疗的情况下，在第10-25%的百分位数处都有正常的线性增长。结论：本研究扩展了HESX1突变的临床特征，表明Asn125Ser杂合子患者可能具有严重的内分泌和神经放射表型，并在生命早期出现类似的畸形特征。版权所有(C)2009 S.Karger AG，巴塞尔
Background/Aims: Mutations in the HESX1 gene are associated with a broad spectrum of phenotypes: septo-optic dysplasia, midline defects, pituitary abnormalities with consequent hypopituitarism, isolated growth hormone (GH) deficiency or combined pituitary hormone deficiencies (CPHD). This study examined the prevalence of mutations in the HESX1 gene in patients with CPHD. Patients/Methods: Sixty patients with sporadic CPHD without septo-optic dysplasia were screened for mutations in HESX1. Results: Three patients were found to be heterozygous for the same Asn125Ser variant in the HESX1 gene. In all 3, panhypopituitarism was presented in the neonatal period, manifested by severe hypoglycemia and neonatal jaundice in 2 patients and respiratory distress in 1. Remarkable findings from physical examination included coarse face; prominent, large, low-set ears; and skeletal abnormalities. Magnetic resonance imaging, performed in 2 patients, revealed a hypoplastic anterior and ectopic posterior pituitary without other midline anomalies. Despite persistent GH deficiency and undetectable levels of insulin-like growth factor 1, all patients had normal linear growth along the 10-25th percentile without GH therapy. Conclusion: The present study expands the clinical picture of HESX1 mutations by demonstrating that patients heterozygous for Asn125Ser may have a severe endocrinologic and neuroradiologic phenotype and similar dysmorphic features appearing very early in life. Copyright (C) 2009 S. Karger AG, Basel