Abstract：
Beckwith-Wiedemann spectrum (BWSp) is caused by genetic and epigenetic alterations on chromosome 11 that regulate cell growth and division. Considering the diverse phenotypic landscape in BWSp, the characterization of the CDKN1C molecular subtype remains relatively limited. Here, we investigate the role of CDKN1C in the broader BWSp phenotype. Notably, patients with CDKN1C variants appear to exhibit a different tumor risk than other BWSp molecular subtypes. We performed a comprehensive literature review using the search term \"CDKN1C Beckwith\" to identify 113 cases of patients with molecularly confirmed CDKN1C-BWSp. We then assessed the genotype and phenotype in a novel cohort of patients with CDKN1C-BWSp enrolled in the BWS Research Registry. Cardinal and suggestive features were evaluated for all patients reported, and tumor risk was established based on available reports. The most common phenotypes included macroglossia, omphalocele, and ear creases/pits. Tumor types reported from the literature included neuroblastoma, acute lymphocytic leukemia, superficial spreading melanoma, and intratubular germ cell neoplasia. Overall, this study identifies unique features associated with CDKN1C variants in BWSp, enabling more accurate clinical management. The absence of Wilms tumor and hepatoblastoma suggests that screening for these tumors may not be necessary, while the neuroblastoma risk warrants appropriate screening recommendations.
摘要：
Beckwith-Wiedemann谱（BWSp）是由11号染色体上的遗传和表观遗传改变引起的，该改变调节细胞生长和分裂。考虑到BWSp中不同的表型景观，CDKN1C分子亚型的表征仍然相对有限.这里,我们研究了CDKN1C在更广泛的BWSp表型中的作用。值得注意的是,与其他BWSp分子亚型相比,具有CDKN1C变异体的患者似乎表现出不同的肿瘤风险.我们使用搜索词“CDKN1CBeckwith”进行了全面的文献综述，以鉴定113例分子证实为CDKN1C-BWSp的患者。然后，我们评估了BWS研究注册的CDKN1C-BWSp患者的基因型和表型。对所有报告的患者进行了基本和暗示特征评估，根据现有报告确定肿瘤风险.最常见的表型包括巨舌，脐膨出,和耳朵折痕/凹坑。文献报道的肿瘤类型包括神经母细胞瘤，急性淋巴细胞白血病，浅表扩散黑色素瘤，和肾小管内生殖细胞瘤。总的来说,这项研究确定了与BWSp中CDKN1C变体相关的独特特征，实现更准确的临床管理。肾母细胞瘤和肝母细胞瘤的不存在表明筛查这些肿瘤可能是不必要的。而神经母细胞瘤的风险需要适当的筛查建议。
