IllnessCNS + PNS tumor syndromes, familial; differential diagnosis

NGS +

[Sanger]

Although sporadic primary neoplasms account for the majority of nervous system tumors, familial tumor syndromes are also clinically relevant. Intracranial malignancies such as meningiomas, glioblastomas, astrocytomas, medulloblastomas, ependymomas, oligodendrogliomas, craniopharyngiomas and pituitary adenomas may each be associated with one or another genetic syndrome. Therefore, the tumors that manifest with these genetic syndromes show quite different phenotypes. They may appear early in life and may be multiple as well. The respective prognosis may be better or worse if these tumors are associated with a familial syndrome such as in neurofibromatosis type 1 + 2, tuberous sclerosis complex, von Hippel-Lindau syndrome, hereditary nonpolyposis-associated colorectal carcinoma, multiple endocrine neoplasia 1 or Gorlin or Li-Fraumeni syndrome, respectively. Peripheral nerve sheath tumors include neurofibromas, schwannomas, meningiomas, vestibular schwannomas and hemangioblastomas. Often autosomal dominant inheritance patterns are observed, rarely autosomal recessive transmission. The molecular genetic diagnostic yields naturally vary widely depending on tumor entities and genetic causes. A negative DNA result does not exclude the clinical diagnosis.

References: DOI 10.1007/s00401-020-02130-0

https://www.uptodate.com/contents/peripheral-nerve-tumors

• Retinoblastoma (RB1)
• Alias: Familial tumour syndromes of the central + peripheral nervous systems
• Allelic: Adenomas, multiple colorectal (MUTYH)
• Allelic: Aplastic anemia (NBN)
• Allelic: Basal cell carcinoma, somatic (PTCH1)
• Allelic: Basal cell nevus syndrome (PTCH1)
• Allelic: Basal cell nevus syndrome (SUFU)
• Allelic: Breast cancer, male, susceptibility to (BRCA2)
• Allelic: Breast cancer, susceptibility to (PALB2)
• Allelic: Breast-ovarian cancer, familial, 2 (BRCA2)
• Allelic: Cardiomyopathy, dilated, 1GG (SDHA)
• Allelic: Coffin-Siris syndrome 3 (SMARCB1)
• Allelic: Coffin-Siris syndrome 5 (SMARCE1)
• Allelic: Cowden syndrome 1 (PTEN)
• Allelic: Erythrocytosis, familial, 2 (VHL)
• Allelic: Fanconi anemia, complementation group N (PALB2)
• Allelic: Goiter, multinodular 1, with/-out Sertoli-Leydig cell tumors (DICER1)
• Allelic: Greig cephalopolysyndactyly syndrome (GLI3)
• Allelic: Holoprosencephaly 7 (PTCH1)
• Allelic: Joubert syndrome 32 (SUFU)
• Allelic: LEOPARD syndrome 1 (PTPN11)
• Allelic: Leukemia, acute lymphoblastic (NBN)
• Allelic: Leukemia, acute myeloid (RUNX1)
• Allelic: Lhermitte-Duclos syndrome (PTEN)
• Allelic: Melanoma, cutaneous malignant, 2 (CDKN2A)
• Allelic: Melanoma-pancreatic cancer syndrome (CDKN2A)
• Allelic: Menke-Hennekam syndrome 1 (CREBBP)
• Allelic: Metachondromatosis (PTPN11)
• Allelic: Mitochondrial complex II deficiency, nuclear type 1 (SDHA)
• Allelic: Neurodegeneration with ataxia + late-onset optic atrophy (SDHA)
• Allelic: Nijmegen breakage syndrome (NBN)
• Allelic: Noonan syndrome 1 (PTPN11)
• Allelic: Noonan syndrome 10 (LZTR1)
• Allelic: Noonan syndrome 2 (LZTR1)
• Allelic: Pallister-Hall syndrome (GLI3)
• Allelic: Pancreatic cancer 2 (BRCA2)
• Allelic: Pancreatic cancer, susceptibility to, 3 (PALB2)
• Allelic: Paragangliomas 5 (SDHA)
• Allelic: Platelet disorder, familial, with associated myeloid malignancy (RUNX1)
• Allelic: Pleuropulmonary blastoma (DICER1)
• Allelic: Polydactyly, postaxial, types A1 + B (GLI3)
• Allelic: Polydactyly, preaxial, type IV (GLI3)
• Allelic: Prostate cancer (BRCA2)
• Allelic: Renal cell carcinoma, somatic (VHL)
• Allelic: Rhabdomyosarcoma, embryonal, 2 (DICER1)
• Allelic: Rubinstein-Taybi syndrome 1 (CREBBP)
• Allelic: Wilms tumor (BRCA2)
• Atypical teratoid/rhabdoid tumors (SMARCA4, SMARCB1)
• Choroid plexus carcinoma (TP53)
• Choroid plexus papilloma (TP53)
• Dysplastic cerebellar gangliocytoma (PTEN)
• Ependymoma (APC, NF1, NF2, TP53)
• Fanconi anemia, complementation group D1 605724 AR 3
• Glioblastoma 3 (BRCA2)
• Glioma susceptibility 1 (TP53)
• Glioma susceptibility 2 (PTEN)
• High-grade gliomas, glioblastomas (MLH1, MSH2, MSH6, PMS2, TP53)
• High-grade gliomas, subtype not specified (ATM, BRCA2, LZTR1, MUTYH, NBN, NF1, TSC2)
• Li-Fraumeni syndrome (TP53)
• Low-grade gliomas (NF1, PMS2, RUNX1)
• Malignant peripheral nerve sheath tumor (NF1)
• Medulloblastoma (APC, BRCA2, CREBBP, GLI3, GPR161, NF2, PALB2, PTCH1, SDHA, SUFU, TP53, VHL)
• Medulloblastoma (BRCA2)
• Medulloblastoma predisposition syndrome (PALB2)
• Medulloblastoma, desmoplastic (SUFU)
• Melanoma + neural system tumor syndrome (CDKN2A, CDKN2B)
• Meningioma (NF2, SMARCE1)
• Meningioma (PTEN)
• Meningioma, familial, susceptibility to (SMARCE1, SUFU)
• Mismatch repair cancer syndrome (MLH1, MSH2, MSH6, PMS2)
• Neurofibromatosis, familial spinal (NF1)
• Neurofibromatosis, type 1 + 2 (NF1 + NF2)
• Optic glioma (NF1)
• Pheochromocytoma (VHL)
• Pilocytic astrocytoma (BRCA2, NBN, PTPN11, TSC2)
• Pineoblastoma (DICER1, RB1)
• Retinoblastoma (RB1)
• Retinoblastoma, trilateral (RB1)
• Rhabdoid tumor predisposition syndrome 1 (SMARCB1)
• Rhabdoid tumors, somatic (SMARCB1)
• Schwannoma (NF2)
• Schwannomatosis, somatic (NF2)
• Schwannomatosis-1, susceptibility to (SMARCB1)
• Schwannomatosis-2, susceptibility to (LZTR1)
• von Hippel-Lindau syndrome (VHL)