IMAGe syndrome is a rare congenital disorder, presenting with intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital anomalies (in males). So far only 17 individuals have been diagnosed molecularly with IMAGe syndrome, this patient is the first case of an individual diagnosed with IMAGe and concurrent rhabdomyosarcoma.

The patient was born at 30 weeks’ gestation and received treatment for hyponatremia and hyperkalemia. At 4 9/12 years of age the patient showed a painless, non-mobile mass on the left thigh. In the biopsy performed a sarcoma weave with solid, nest-like growth, with characteristics of rhabdomyosarcoma was identified. The family history and physical examination indicated IMAGe syndrome so genetic testing was requested. A whole exome sequencing procedure with use of SureSelectXT Human ALL Exon V7, confirmed a single nucleotide variant NM_000076.2(CDKN1C):c.820G>A (p.Asp274Asn); identifying a missense mutation in the imprinted gene CDKN1C associated with IMAGe syndrome. Although tumours associated with CDKN1C are rare, deregulation of imprinted genes is increasingly being recognised as a mechanism of tumorigenesis in cancer; chromosomal region 11p15.5 contains a cluster of imprinted genes. This same region is the most consistent site of allele loss in rhabdomyosarcoma and is the same region altered in both IMAGe and Beckwith-Wiedemann syndrome. Molecular studies have found genetic changes in the 11p15 region in a variety of embryonal tumours like Wilms tumours which are commonly developed in Beckwith-Wiedemann syndrome and embryonal rhabdomyosarcoma.

Through this case we aim to present the possibility of oncogenesis in patients with IMAGe syndrome, specifically rhabdomyosarcoma.

IMAGe 综合征是一种罕见的先天性疾病，表现为宫内生长受限、干骺端发育不良、先天性肾上腺发育不良和生殖器异常（男性）。到目前为止，只有 17 人被分子诊断为 IMAGe 综合征，该患者是第一例被诊断为 IMAGe 并并发横纹肌肉瘤的患者。

患者出生于妊娠 30 周，并接受了低钠血症和高钾血症的治疗。患者在 4 9/12 岁时出现左大腿无痛、不能活动的肿块。在活检中，肉瘤组织呈实心、巢状生长，具有横纹肌肉瘤的特征。家族史和体格检查显示 IMAGe 综合征，因此要求进行基因检测。使用 SureSelectXT Human ALL Exon V7 的全外显子组测序程序证实了单核苷酸变异 NM_000076.2(CDKN1C):c.820G>A (p.Asp274Asn)；鉴定与 IMAGe 综合征相关的印记基因CDKN1C中的错义突变。尽管与CDKN1C相关的肿瘤在罕见的情况下，印迹基因的失调越来越被认为是癌症发生的一种机制；染色体区域 11p15.5 包含一组印迹基因。这个相同的区域是横纹肌肉瘤中最一致的等位基因丢失位点，并且是 IMAGe 和 Beckwith-Wiedemann 综合征中改变的相同区域。分子研究发现，多种胚胎性肿瘤的 11p15 区域发生遗传变化，如通常在 Beckwith-Wiedemann 综合征和胚胎性横纹肌肉瘤中发生的 Wilms 瘤。

通过这个案例，我们旨在展示 IMAGe 综合征患者发生肿瘤的可能性，特别是横纹肌肉瘤。