Donohue syndrome (DS) and Rabson-Mendenhall syndrome (RMS) are rare diseases caused by biallelic variants within the insulin receptor gene (INSR). Here, we report 2 cases: one with DS and the other with RMS. The case with DS presented with intrauterine growth retardation, nipple hypertrophy, clitoromegaly, distended abdomen, hypertrichosis, and dysmorphic features. The second case showed severe acanthosis nigricans, hyperkeratosis, and hypertrichosis. In both cases, abnormal glucose homeostasis due to severe insulin resistance was observed. The diagnosis of DS and RMS was established based on clinical characteristics, abnormal glucose homeostasis, high serum insulin levels, and determination of pathogenic variants in the INSR gene. The first case with DS has 2 novel homozygous variants, NM_000208.3, c.3122delA (p.N1041Mfs*16) and c.3419C>G (p.A1140G), and the second case with RMS has a previously reported homozygous variant NM_000208.3, c.3529+5G>A (IVS19+5G>A) in the INSR gene.

中文翻译：

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在两个严重的胰岛素抵抗综合征患者中，胰岛素受体基因有两个新的变异和一个先前报道的变异。

Donohue综合征（DS）和Rabson-Mendenhall综合征（RMS）是由胰岛素受体基因（INSR）中的双等位基因变异引起的罕见疾病。在这里，我们报告2种情况：一种是DS，另一种是RMS。DS病例表现为宫内发育迟缓，乳头肥大，阴蒂肿大，腹部膨大，肥大症和畸形。第二例显示严重黑棘皮病，角化过度和肥大症。在这两种情况下，均观察到由于严重的胰岛素抵抗引起的异常葡萄糖稳态。DS和RMS的诊断是基于临床特征，异常葡萄糖稳态，高血清胰岛素水平以及INSR基因中致病变异的确定而建立的。DS的第一种情况具有2个新的纯合子变体NM_000208.3，c.3122delA（p.N1041Mfs * 16）和c.3419C> G（p。