PAX3/7-FOXO1 fusion-negative alveolar rhabdomyosarcoma (ARMS) developed in a patient presenting with intellectual disability and dysmorphic facial features. Whole exome sequencing analysis of a germline sample identified a PACS1 c.607 C>T de novo variant and the patient was diagnosed with Schuurs-Hoeijmakers syndrome (SHS). SHS is a rare disease characterized by intellectual disability and dysmorphic facial features, among various physical abnormalities, due to PACS1 c.607 C>T de novo variant. Due to the rarity of the SHS, diagnosis based on phenotypic information is difficult. To date, there have been no previous reports describing malignancy associated with SHS. Comprehensive somatic mutation analysis revealed a unique pattern of genetic alterations in the PAX3/7-FOXO1 fusion-negative ARMS tumor, including mutations in the oncogene, HRAS; MYOD1, a molecule essential for muscle differentiation; and KMT2C and TET1, genes encoding factors involved in epigenetic regulation. Although the role of PACS1 in tumorigenesis is unclear, it is reported to function in apoptosis regulation. Our case suggests that PACS1 could have a novel role in oncogenesis.

PAX3 / 7 - FOXO1融合阴性肺泡横纹肌肉瘤 (ARMS) 发生于一名智力残疾和畸形面部特征的患者身上。生殖系样本的全外显子组测序分析鉴定出PACS1 c.607 C>T 从头变异，患者被诊断为 Schuurs-Hoeijmakers 综合征 (SHS)。SHS 是一种罕见的疾病，其特征是智力障碍和畸形面部特征，在各种身体异常中，由于PACS1c.607 C>T 从头变体。由于 SHS 的罕见性，基于表型信息的诊断很困难。迄今为止，之前没有关于与 SHS 相关的恶性肿瘤的报道。综合体细胞突变分析揭示了PAX3 / 7 - FOXO1融合阴性 ARMS 肿瘤的独特遗传改变模式，包括致癌基因HRAS的突变；MYOD1，一种对肌肉分化至关重要的分子；和KMT2C和TET1，基因编码参与表观遗传调控的因子。尽管 PACS1 在肿瘤发生中的作用尚不清楚，但据报道它在细胞凋亡调节中起作用。我们的案例表明 PACS1 可能在肿瘤发生中具有新的作用。