Pathogenic germline DICER1 variants are associated with pleuropulmonary blastoma, multinodular goiter, embryonal rhabdomyosarcoma and other tumour types, while mosaic missense DICER1 variants in the RNase IIIb domain are linked to cause GLOW (global developmental delay, lung cysts, overgrowth, and Wilms’ tumor) syndrome. Here, we report four families with germline DICER1 pathogenic variants in which one member in each family had a more complex phenotype, including skeletal findings, facial dysmorphism and developmental abnormalities. The developmental features occur with a variable expressivity and incomplete penetrance as also described for the neoplastic and dysplastic lesions associated with DICER1 variants. Whole exome sequencing (WES) was performed on all four cases and revealed no further pathogenic or likely pathogenic dominant, homozygous or compound heterozygous variants in three of them. Notably, a frameshift variant in ARID1B was detected in one patient explaining part of her phenotype. This series of patients shows that pathogenic DICER1 variants may be associated with a broader phenotypic spectrum than initially assumed, including predisposition to different tumours, skeletal findings, dysmorphism and developmental abnormalities, but genetic work up in syndromic patients should be comprehensive in order not to miss additional underlying /modifying causes.

致病性种系DICER1变异与胸膜肺母细胞瘤、多结节性甲状腺肿、胚胎性横纹肌肉瘤和其他肿瘤类型相关，而 RNase IIIb 结构域中的嵌合错义DICER1变异与导致 GLOW（整体发育迟缓、肺囊肿、过度生长和肾母细胞瘤）相关综合症。在这里，我们报告了四个具有种系DICER1致病性变异的家族，其中每个家族的一名成员具有更复杂的表型，包括骨骼异常、面部畸形和发育异常。发育特征具有可变的表达性和不完全的外显率，正如与DICER1变异相关的肿瘤性和发育异常性病变所描述的那样。对所有四个病例进行了全外显子组测序（WES），结果显示其中三个病例没有进一步致病或可能致病的显性、纯合或复合杂合变异。值得注意的是，在一名患者中检测到ARID1B 的移码变异，这解释了她的部分表型。这一系列患者表明，致病性DICER1变异可能与比最初假设的更广泛的表型谱相关，包括不同肿瘤的易感性、骨骼发现、畸形和发育异常，但综合征患者的基因检查应该是全面的，以免错过其他潜在/改变原因。