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基于分子诊断和分子分型的遗传性嗜铬细胞瘤（PHEO）和副神经节瘤（PGL）综合征（PPGLs）的个体化精准管理日益得到关注和实践。近年来新发现的 MAX胚系突变相关PPGLs，呈常染色体显性遗传，临床罕见。为提高认识并探索个体化的有效诊治措施，本文系统复习了2011年1月至2024年2月发表的相关文献，累计77个 MAX胚系突变家系共101例患者。 MAX胚系突变分属于44种突变类型，涉及 MAX的所有5个外显子，多集中于第3、4号外显子（64.0%，65/101）；主要为无义突变和错义突变（72.3%）、部分为大片段缺失和内含子变异，基因融合突变少见；约10%的家系患者中存在亲本起源效应。101例患者中，96例（95.0%）发生PHEO，双侧61例，单侧35例；诊断年龄为（31.7±10.9）岁（范围：13~80）岁，男女比例1.2∶1；其中15例为转移性PHEO。11例合并胸腹部PGL。8例（7.9%）合并功能性垂体腺瘤。12例（11.9%）发生其他神经内分泌肿瘤（NET），其中合并PHEO 8例（甲状旁腺功能亢进4例，神经母细胞瘤、盆腔神经节神经母细胞瘤/神经节细胞瘤、甲状腺髓样癌和C细胞增生各1例）。6例（5.9%）合并非NET包括舌鳞状细胞癌、甲状腺乳头状癌、前列腺癌、肾嗜酸性细胞瘤、乳腺癌合并肾嗜酸性细胞瘤、胸软骨肉瘤合并多灶性肺腺癌各1例。另5例（5.0%）突变者不合并PHEO，其中4例仅发生单一的其他NET（神经节细胞瘤2例、腹部神经母细胞瘤1例、胰腺NET 1例），1例儿童为无症状携带者。 MAX突变相关PPGLs，发病年龄小，外显率高，表型独特，可能是一种新型多发性内分泌肿瘤（MEN）或是MEN 5型。所有 MAX突变者应进行PPGL、垂体腺瘤、甲状旁腺功能亢进和（或）神经节神经瘤（神经母细胞瘤）等神经嵴起源疾病的全面基线评估，并考虑双侧和（或）PHEO转移的风险。对PPGLs合并如功能性垂体腺瘤等其他NET的患者，应进行至少包括 MAX基因在内的遗传学检测和家系筛查。

The individualized precision management of hereditary pheochromocytoma (PHEO) and paraganglioma (PGL) syndromes (PPGLs) based on molecular diagnosis and molecular subtype is becoming more popular. The newly discovered MAX germline mutation-associated PPGLs are autosomally dominant and rare. To raise awareness and explore the effective management of individual diagnosis and treatment, the relevant literature published between January 2011 and February was systematically reviewed. There were a total of 101 patients in the 77 families, involving all 5 exons, containing 44 types of MAX germline mutations and mostly concentrated in exons 3 and 4 (64.4%), the main mutations were nonsense mutations and missense mutations (73.2%), and some were large fragment deletions or insertions, intron variant, gene fusion mutations were relatively infrequent. Furthermore, about 10% of the patients had a paternal parent-of-origin effect. Among the 101 patients, 96 (95.0%) developed PHEO including 15 metastatic PHEO, 61 bilateral PHEO and 35 unilateral PHEO. The age of diagnosis was (31.7±10.9) years (range: 13 to 80 years). The male to female ratio was 1.2∶1. Eleven were accompanied with chest and abdominal PGL. Eight (7.9%) were accompanied by functional pituitary adenoma. And 12 (11.9%) developed other neuroendocrine tumors (NET), of which 8 were accompanied by PHEO, including 4 hyperparathyroidism, 1 gangliocytoma and neuroblastoma, 1 pancreatic NET, 1 medullary thyroid carcinoma and 1 C cell hyperplasia. Six presented concomitant non-NET, including 1 tongue squamous cell carcinoma, 1 papillary thyroid carcinoma, 1 prostate cancer, 1 renal oncocytoma, 1 breast cancer with renal oncocytoma, and 1 thoracic chondrosarcoma with multifocal adenocarcinoma of lung. The remaining 5 cases (5.0%), including 4 other NET (2 ganglioblastoma, 1 abdominal neuroblastoma and 1 pancreatic NET) and 1 asymptomatic child, did not present PHEO. The MAX germline mutation may cause a novel multiple endocrine neoplasia, which can be described as type 5. A comprehensive baseline assessment of neural crest cell-derived diseases such as PPGL, pituitary adenoma, hyperparathyroidism, and/or gangliocytoma (neuroblastoma) was recommended for all people with MAX germline mutations, and the risk of bilateral and/or metastatic PHEO should also be considered. In contrast, patients with PPGLs combined with other NET, such as functional pituitary adenoma, should undergo genetic testing and pedigree screening that includes at least the MAX gene.