Gonsalves Rob, Aleck Kirk, Newbern Dorothee, Shaibi Gabriel, Kapadia Chirag, Oatman Oliver
Division of Endocrinology, Phoenix Children's Hospital, Phoenix, Arizona, USA.
Division of Genetics, Phoenix Children's Hospital, Phoenix, Arizona, USA.
Endocrinol Diabetes Metab Case Rep. 2020 Oct 6;2020. doi: 10.1530/EDM-20-0042.
Single-minded homolog 1 (SIM1) is a transcription factor that plays a role in the development of both the hypothalamus and pituitary. SIM1 gene mutations are known to cause obesity in humans, and chromosomal deletions encompassing SIM1 and other genes necessary for pituitary development can cause a Prader-Willi-like syndrome with obesity and hypopituitarism. There have been no reported cases of hypopituitarism linked to a single SIM1 mutation. A 21-month-old male presented to endocrinology clinic with excessive weight gain and severe obesity. History was also notable for excessive drinking and urination. Endocrine workup revealed central hypothyroidism, partial diabetes insipidus, and central adrenal insufficiency. Genetic evaluation revealed a novel mutation in the SIM1 gene. No other genetic abnormalities to account for his obesity and hypopituitarism were identified. While we cannot definitively state this mutation is pathogenic, it is notable that SIM1 plays a role in the development of all three of the patient's affected hormone axes. He is now 6 years old and remains on treatment for his pituitary hormone deficiencies and continues to exhibit excessive weight gain despite lifestyle interventions.
Mutations in SIM1 are a well-recognized cause of monogenic human obesity, and there have been case reports of Prader-Willi-like syndrome and hypopituitarism in patients with chromosomal deletions that contain the SIM1 gene. SIM1 is expressed during the development of the hypothalamus, specifically in neuroendocrine lineages that give rise to the hormones oxytocin, arginine vasopressin, thyrotropin-releasing hormone, corticotropin-releasing hormone, and somatostatin. Pituitary testing should be considered in patients with severe obesity and a known genetic abnormality affecting the SIM1 gene, particularly in the pediatric population.
单 minded 同源物 1（SIM1）是一种转录因子，在下丘脑和垂体的发育中起作用。已知 SIM1 基因突变会导致人类肥胖，包含 SIM1 和垂体发育所需其他基因的染色体缺失可导致伴有肥胖和垂体功能减退的普拉德 - 威利样综合征。尚无与单一 SIM1 突变相关的垂体功能减退病例报道。一名 21 个月大的男性因体重过度增加和严重肥胖就诊于内分泌科。病史中还存在过度饮水和多尿的情况。内分泌检查发现中枢性甲状腺功能减退、部分性尿崩症和中枢性肾上腺功能不全。基因评估发现 SIM1 基因存在一种新突变。未发现其他可解释其肥胖和垂体功能减退的基因异常。虽然我们不能确定该突变是致病的，但值得注意的是 SIM1 在患者所有三个受影响的激素轴的发育中都起作用。他现在 6 岁，仍在接受垂体激素缺乏的治疗，尽管进行了生活方式干预，但体重仍持续过度增加。
SIM1 突变是单基因人类肥胖的一个公认原因，并且有病例报告称含有 SIM1 基因的染色体缺失患者会出现普拉德 - 威利样综合征和垂体功能减退。SIM1 在下丘脑发育过程中表达，特别是在产生催产素、精氨酸加压素、促甲状腺激素释放激素、促肾上腺皮质激素释放激素和生长抑素的神经内分泌谱系中。对于患有严重肥胖且已知有影响 SIM1 基因的遗传异常的患者，尤其是儿科患者，应考虑进行垂体检查。
