Abstract：
Coffin-Siris syndrome (CSS) is a rare neurodevelopmental and multisystemic disorder with wide genetic heterogeneity and phenotypic variability caused by pathogenic variants in the BAF complex with 341 cases enrolled in the CSS/BAF-related disorders registry by 2021. Pathogenic variants of ARID1A account for 7-8% of cases with CSS phenotype. Malignancy has been previously reported in six individuals with CSS associated with BAF mutations. Two of these malignancies including one acute lymphoid leukemia and one hepatoblastoma were reported in ARID1A-associated CSS (ARID1A-CSS). Alterations in ARID1A are among the most common molecular aberrations in human cancer. Somatic deletion of 1p and specifically of 1p36.11 containing ARID1A is frequently seen in hepatoblastoma and has been associated with high-risk features. Here we report a child with CSS Phenotype and a novel de novo variant of ARID1A with hepatoblastoma. Because hepatoblastoma has an incidence of 1 per million children, the presence of hepatoblastoma in 2 of 30 known cases of ARID1A-CSS is significant. ARID1A-CSS should be included among the cancer predisposition syndromes associated with an increased risk of hepatoblastoma and tumour surveillance considered for these patients. The role of ARID1A in the pathogenesis and outcome of hepatoblastoma deserves further investigation.
摘要：
Coffin-Siris综合征（CSS）是一种罕见的神经发育和多系统疾病，具有广泛的遗传异质性和表型变异性，由BAF复合体中的致病变异引起，到2021年有341例纳入CSS/BAF相关疾病注册表。ARID1A的致病变体占CSS表型病例的7-8%。先前已经在六个具有与BAF突变相关的CSS的个体中报道了恶性肿瘤。在ARID1A相关的CSS（ARID1A-CSS）中报道了其中两种恶性肿瘤，包括一种急性淋巴样白血病和一种肝母细胞瘤。ARID1A的改变是人类癌症中最常见的分子畸变。在肝母细胞瘤中经常出现1p和特别是含有ARID1A的1p36.11的体细胞缺失，并且与高风险特征有关。在这里，我们报告了一个患有CSS表型和ARID1A肝母细胞瘤的新型从头变异的孩子。因为肝母细胞瘤的发病率为每百万儿童中1人，在30例已知的ARID1A-CSS病例中,有2例存在肝母细胞瘤是显著的.ARID1A-CSS应包括在与这些患者的肝母细胞瘤和肿瘤监测风险增加相关的癌症易感性综合征中。ARID1A在肝母细胞瘤的发病机制和预后中的作用值得进一步研究。
