Table 1.
Increased incidence of MDS in pediatric syndromes associated with defective DNA repair.
| Process Involved | Disease | Gene(s) Involved * | Incidence of Disease | Incidence of MDS in Patients § |
|---|---|---|---|---|
| DNA damage response and cell cycle checkpoint | Li-Fraumeni syndrome [135] | TP53 or CHEK2 | 400 Cases reported | 3 Cases reported |
| DSB repair | ||||
| Global | Ataxia Telangiectasia [136] | ATM | 1/100,000 to 40,000 | Not reported |
| HR | Bloom syndrome [124] | BLM, BLAP75/RMI1 | 1/48,000 | 4 Cases reported |
| Rothmund-Thomson syndrome [125,126,127,128] | RECQL4 | 300 Cases reported | 4 Cases reported | |
| Werner syndrome [129,130] | WRN | 1300 Cases reported | 6 Cases reported | |
| FA pathway | Fanconi anemia [122] | FANC(A–G) | 1/350,000 | 20.7% |
| NHEJ | Lig4 syndrome [137] | LIG4 | Few cases reported | 1 Case reported |
| NER | Xeroderma Pigmentosa [136] | XP | 1/250,000 | Not reported |
| Other ¶ | ||||
| Unclear | Neurofibromatosis type 1 [138] | NF1 | 1/3500 | 200–500-Fold increase in children |
| Shwachman-Diamond syndrome [139,140,141] | SBDS | 1/50,000 | 8%–33% | |
| Telomere maintenance | Dyskeratosis congenital [142,143,144] | DKC1, NOP10, NHP2, TERC, TERT, TINF2 | 1/1,000,000 | 4%–5% |
| Oxidative DNA damage repair | Down syndrome [145,146,147] | Trisomy 21 | 1/1000 to 1/650 | 1/1000 to 1/500 |
* Genes involved are the genes thought to be directly responsible for the genetic syndrome mentioned in the corresponding “disease” column; § Most of these diseases present themselves in early childhood. The overall incidence of de novo MDS in children is ~1.8–4 per 1,000,000 [148]; ¶ Although these diseases are not considered classical DNA repair-deficiency disorders, patients suffering from them have shown either a compromised DNA damage response or increased potential to acquire DNAlesions [139,146,149,150]; Part of this table was published previously in [112].