Table 1.
Cancer predisposition syndromes associated to pediatric medulloblastoma and their related molecular, pathological, clinical, and prognostic features.
| Predisposition genes | Cancer syndrome | MB prevalence (%) | MB median age at diagnosis (years) | Molecular subgroup | MB histologic subtype | Clinical features | 5 year-OS(%) | References |
|---|---|---|---|---|---|---|---|---|
| PTCH1 | Gorlin | <2–4.5 | 2 | SHH | Desmoplastic/nodular with extensive nodularity |
Palmar or plantar pits, odontogenic keratocysts, basal cell carcinomas | 85* | Waszak et al. (23) |
| SUFU | Gorlin | 2–33 | 2 | SHH | Desmoplastic/nodular with extensive nodularity |
Palmar or plantar pits, odontogenic keratocysts, basal cell carcinomas | 85* | Waszak et al. (23); Smith et al (24) |
| TP53 | Li Fraumeni | 1 | 9.8 | SHH WNT |
LCA, Classic | Soft tissue sarcomas, osteosarcomas, glioblastomas/astrocytomas, choroid plexus carcinomas, breast cancers | 27 | Waszak et al. (23); Zhukova et al. (25) |
| MLH1, MSH2, MSH6, PMS1, PMS2 | Turcot type1 | unknown | unknown | unknown | unknown | Café-au-lait spots | unknown | |
| APC | Turcot type2 | 1 | 9.2 | WNT SHH (rarely) |
Classic | Gastrointestinal symptoms (diarrhea, constipation), neurological symptoms (headache, vomiting, visual and/or hearing and/or sensorimotor deficits) | 80-100 | Waszak et al. (23); Surun et al. (26) |
| BRCA2 | unknown | 1 | 5.7 | SHH WNT SHH |
Classic, desmoplastic/nodular, LCA, with extensive nodularity Classic |
unknown Fanconi Anemia phenotype (biallelic mutations) |
25**;100*** | Waszak et al. (23) Present report Present report |
| PALB2 | unknown | <1 | SHH Group3 Group 4 |
unknown | unknown | 75 | Waszak et al. (23) | |
| GPR161 | unknown | 3.4**** | unknown | SHH | unknown | unknown | unknown | Tischkowitz et al. (27) |
| ELP1 | unknown | unknown | 6.3 | SHH | Desmoplastic/nodular | unknown | 92 | Hwang et al. (28) |
| CREBBP; EP300 | Rubinstein-Taybi | 0.05***** | unknown | Group3***** | unknown | Growth retardation, obesity, facial, skeletal and neurological anomalies, cognitive/psychiatric disorders, pilomatricomas | unknown | Carter et al. (29) |
* cumulative PTCH1 and SUFU.
** compound heterozygous BRCA2.
*** heterozygous germline BRCA2.
**** referred to patients with MBSHH subgroup.
***** limited data.