Servicio de Oncología Radioterápica Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain.
Servicio de Oncología Médica Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain.
Eur J Med Genet. 2022 Jan;65(1):104399. doi: 10.1016/j.ejmg.2021.104399. Epub 2021 Nov 15.
Fanconi anemia is primarily inherited as an autosomal recessive genetic disorder with common delays in diagnosis and challenging treatments. Fanconi anemia patients have a high risk of developing solid tumors, particularly in the head and neck or anogenital regions. The diagnosis of Fanconi anemia is primarily based on the chromosomal breakage but FA gene sequencing is recommended in all patients with a positive chromosome fragility test. Here, we present a 32-year-old man with advanced tonsil squamous cell carcinoma and fatal toxicity after the first cycle of chemotherapy. No anemia was present. A recent variant mutation if the FANCM gene was detected (c1511_1515delGAGTA (pArg504AsnfsTer29)). Homozygous or double heterozygous pathogenic variants have been reported in FANCM and linked to azoospermia and primary ovarian failure without anemia. Alterations in this gene have also been associated with a genetic predisposition for solid tumors (breast and ovarian cancer) and hematological malignancies (B-cell acute lymphoblastic leukemia). Due to the hypersensitivity of these patients to DNA-damaging agents such as chemotherapy and radiotherapy, surgery is the best treatment option for malignant solid tumors. Dose reductions or alternative regimens of chemotherapy and/or radiotherapy are recommended in FA patients who develop a malignant tumor.
范可尼贫血症主要作为一种常染色体隐性遗传疾病遗传,其诊断通常会延迟,治疗也极具挑战性。范可尼贫血症患者有很高的罹患实体肿瘤的风险,尤其是在头颈部或肛生殖区域。范可尼贫血症的诊断主要基于染色体断裂,但建议所有染色体脆性试验阳性的患者进行 FA 基因测序。在此,我们报告了一例 32 岁男性,患有晚期扁桃体鳞状细胞癌,在第一周期化疗后出现致命毒性。没有贫血。最近检测到 FANCM 基因的变异突变(c1511_1515delGAGTA(pArg504AsnfsTer29))。FANCM 中的纯合子或双杂合子致病性变异已被报道,并与无贫血的无精子症和原发性卵巢功能衰竭相关。该基因的改变也与实体肿瘤(乳腺癌和卵巢癌)和血液系统恶性肿瘤(B 细胞急性淋巴细胞白血病)的遗传易感性相关。由于这些患者对化疗和放疗等 DNA 损伤剂高度敏感,因此手术是治疗恶性实体肿瘤的最佳选择。对于发生恶性肿瘤的 FA 患者,建议减少化疗和/或放疗的剂量或选择替代方案。