Retinoblastoma is a malignancy of the eye in children characterized by biallelic inactivation of the retinoblastoma 1 gene (RB1), located at chromosome 13q14.2. Children with interstitial chromosome 13q deletions that include the RB1 gene show a predisposition to develop retinoblastoma and variable other features. Large 13q deletions with severe clinical phenotype are nearly always the result of a de novo mutation, i.e. the pathogenic alteration is not detected in parents. This results in a low risk for siblings to develop 13q deletion syndrome. Here, we describe a patient with profound muscle hypotonia, severe developmental delay and bilateral retinoblastoma carrying a large deletion in 13q13.3q14 with the size of 16 Mb, involving the RB1 gene. Neither parent showed retinoblastoma, muscle hypotonia or developmental delay. Chromosome analysis and Fluorescence in situ hybridization (FISH) showed a balanced complex chromosomal rearrangement (CCR) between chromosome 12 and 13 [ins(12;13)(q21.2;q12.3q14.3)] and an additional balanced translocation of chromosome 7 and 15 [t(7;15)(q31.2;q25.3)] in the healthy father. Malsegregation of the paternal insertional translocation involving chromosome 12 and 13 resulted in a 13q deletion syndrome of the child [46,XY,ins(12;13)(q21.2;q12.3q14.3)]. Balanced translocations in parents are a rare cause of de novo RB1 deletions in offspring. This case report emphasizes the need for parental chromosomal analysis and FISH in parents of children diagnosed with 13q deletion syndrome or large RB1 gene deletions to precisely determine the recurrence risk in siblings. Guidelines for genetic testing should be revised accordingly.

中文翻译：

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父亲染色体平衡重排导致的13q缺失综合征：父母核型分析的意义。

视网膜母细胞瘤是一种儿童眼部恶性肿瘤，其特征是位于染色体 13q14.2 的视网膜母细胞瘤 1 基因 (RB1) 双等位基因失活。包括 RB1 基因在内的间质染色体 13q 缺失的儿童表现出发展成视网膜母细胞瘤和可变其他特征的倾向。具有严重临床表型的大 13q 缺失几乎总是从头突变的结果，即在父母中未检测到致病性改变。这导致兄弟姐妹患 13q 缺失综合征的风险较低。在这里，我们描述了一名患有严重肌肉张力减退、严重发育迟缓和双侧视网膜母细胞瘤的患者，该患者在 13q13.3q14 中携带一个大小为 16 Mb 的大缺失，涉及 RB1 基因。父母均未出现视网膜母细胞瘤、肌张力减退或发育迟缓。染色体分析和荧光原位杂交 (FISH) 显示染色体 12 和 13 [ins(12;13)(q21.2;q12.3q14.3)] 之间存在平衡的复杂染色体重排 (CCR) 和染色体的额外平衡易位7 和 15 [t(7;15)(q31.2;q25.3)] 在健康的父亲中。涉及 12 号和 13 号染色体的父系插入易位错误分离导致儿童出现 13q 缺失综合征 [46,XY,ins(12;13)(q21.2;q12.3q14.3)]。父母的平衡易位是后代 RB1 从头缺失的罕见原因。本病例报告强调需要对诊断为 13q 缺失综合征或大 RB1 基因缺失的儿童的父母进行父母染色体分析和 FISH，以准确确定兄弟姐妹的复发风险。基因检测指南应相应修订。