Loh Jerold, Ong Pei Yi, Goh Denise Li Meng, Puhaindran Mark E, Vellayappan Balamurugan A, Ow Samuel Guan Wei, Chan Gloria, Lee Soo-Chin
Department of Haematology-Oncology, NCIS, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore.
Division of Paediatric Genetics and Metabolism, Department of Paediatrics, Khoo Teck Puat - National University Children's Medical Institute, National University Hospital, Singapore, Singapore.
Hered Cancer Clin Pract. 2022 Jun 13;20(1):23. doi: 10.1186/s13053-022-00230-4.
Peripheral Nerve Sheath Tumors (PNST) are a diverse group of mostly benign tumours uncommon in the general population. About 5-10% of PNSTs are hereditary, predominantly arising from germline variants in NF1, NF2, SMARCB1, or LZTR1 gene.
We reviewed the clinical characteristics and genetic testing results of patients referred to the NCIS Adult Cancer Genetics Clinic for suspected hereditary PNST.
3,001 patients suspected to have various hereditary cancer syndromes were evaluated between year 2000 to March 2021. 13 (0.4%) were clinically diagnosed to have hereditary PNSTs. The majority were male (54%), with a median age at presentation to the genetics clinic of 29 years (range 19-48). 11/13 (85%) patients had multiple PNSTs, 12/13 (92%) had young onset PNSTs, 5/13 (38.5%) had personal and family history of PNST. 11/13 patients (85%) had clinical features of neurofibromatosis type 1 (NF1) including one patient who also fulfilled clinical criteria of neurofibromatosis type 2 (NF2); 2/13 (14%) had multiple schwannomas. Four patients underwent multi-gene panel testing, including one patient with clinical NF1, one patient who met both clinical NF1 and NF2 criteria, and two patients with multiple schwannomas. The patient with clinical features of NF1 was heterozygous for a pathogenic c. 2033dup variant in the NF1 gene. The patient with both NF1/NF2 features was heterozygous for a novel c.732 T > A nonsense variant in the NF2 gene. The two patients with multiple schwannomas were heterozygous for a pathogenic/likely pathogenic variant in the LZTR1 gene and are the first LZTR1-positive schwannomatosis patients reported in Asia.
Hereditary PNSTs are rare referrals to an adult cancer genetics clinic. NF1 is the most common PNST seen. LZTR1 variants may be the underlying cause in Asian patients with multiple schwannomatosis.
周围神经鞘瘤（PNST）是一组多样的肿瘤，大多为良性，在普通人群中并不常见。约5%-10%的PNST是遗传性的，主要源于NF1、NF2、SMARCB1或LZTR1基因的种系变异。
我们回顾了转诊至NCIS成人癌症遗传学诊所疑似遗传性PNST患者的临床特征和基因检测结果。
2000年至2021年3月期间，对3001名疑似患有各种遗传性癌症综合征的患者进行了评估。13名（0.4%）临床诊断为遗传性PNST。大多数为男性（54%），到遗传学诊所就诊时的中位年龄为29岁（范围19-48岁）。13名患者中有11名（85%）患有多发性PNST，13名中有12名（92%）为早发性PNST，13名中有5名（38.5%）有PNST的个人和家族史。13名患者中有11名（85%）具有1型神经纤维瘤病（NF1）的临床特征，其中一名患者还符合2型神经纤维瘤病（NF2）的临床标准；13名中有2名（14%）患有多发性神经鞘瘤。4名患者接受了多基因检测，包括一名具有临床NF1特征的患者、一名同时符合临床NF1和NF2标准的患者以及两名患有多发性神经鞘瘤的患者。具有NF1临床特征的患者在NF1基因中存在致病性c.2033dup变异的杂合子。同时具有NF1/NF2特征的患者在NF2基因中存在一种新的c.732 T>A无义变异的杂合子。两名患有多发性神经鞘瘤的患者在LZTR1基因中存在致病性/可能致病性变异的杂合子，是亚洲报道的首例LZTR1阳性神经鞘瘤病患者。
遗传性PNST很少转诊至成人癌症遗传学诊所。NF1是最常见的PNST类型。LZTR1变异可能是亚洲多发性神经鞘瘤病患者的潜在病因。
