Table 4.
Clinical phenotype and family history of patients with P/LP germ line, per ACMG/AMP criteria, causative of a congenital syndrome/disorder
| Patient ID | Age/sex | Germ line mutated gene |
Congenital syndrome/disorder | Diagnosis | Extrahematologic phenotype | Family history |
|
|---|---|---|---|---|---|---|---|
| Hematologic/solid cancer | Other | ||||||
| PV1185 | 51/F |
CSF3R CSF3R |
SCN | ICUS | Connective tissue disease treated with methotrexate | — | — |
| PV1395 | 82/M | DDX41 | DDX41-associated predisposition | MDS-MLD | Hyperthyroidism treated with radiometabolic therapy | — | — |
| PV1583 | 56/F | DDX41 | DDX41-associated predisposition | MDS-EB-2 | — | — | — |
| PV1336 | 59/M | DDX41 | DDX41-associated predisposition | MDS-EB-2 | — | — | — |
| PV1475 | 66/M | DDX41 | DDX41-associated predisposition | MDS-EB-2 | — | — | — |
| PV10015 | 62/M | DDX41 | DDX41-associated predisposition | AML | Colon cancer treated with chemotherapy | Mother with colon and uterine cancers | — |
| PV1178 | 57/M | DDX41 | DDX41-associated predisposition | MDS-EB-2 | — | — | — |
| PV1581 | 64/M | DDX41 | DDX41-associated predisposition | MDS-EB-2 | — | — | — |
| PV693 | 49/M | DDX41 | DDX41-associated predisposition | MDS-EB-2 | — | — | — |
| PV1591 | 66/M | DDX41 | DDX41-associated predisposition | MDS-EB-2 | Cardiomyopathy | — | — |
| PV2607 | 65/M | DDX41 | DDX41-associated predisposition | ICUS | Chronic gastritis HP+; APCA-positive | — | — |
| PV583 | 73/M | DDX41 | DDX41-associated predisposition | MDS-MLD | — | — | — |
| PV554 | 60/M | DDX41 | DDX41-associated predisposition | CCUS | — | — | — |
| PV1546 | 35/M | ELANE | SCN | MDS-MLD | Mild splenomegaly | Father with MDS died after bone marrow transplant | Brother with isolated neutropenia |
| PV2613 | 54/F |
FANCA FANCA |
FA | MDS-MLD | Short stature, triangular facies, small head café au lait spots, hypertrichosis, learning disabilities; spinocellular cell and genital carcinoma | Brother with BMF died at age 10 | Father with low platelet counts died of intracranial bleeding |
| PV2443 | 37/F | FANCA∗ | FA | MDS-MLD | Short stature; intrauterine fetal death (seventh month); hepatic steatosis | — | — |
| PV1047 | 45/M | FANCA | FA | MDS-EB-1 | — | — | — |
| PV10061 | 41/F | FANCG | FA | ICUS | Short stature intellectual disability, congenital right hearing loss, horseshoe kidney; polyabortivity; squamous cell carcinoma | One brother with ALL and 1 brother with esophagus cancer died at age 33; mother with breast cancer died at age 56 | — |
| PV2292 | 32/M | GATA1∗ | DBA | ICUS | — | Sister with primary myelofibrosis | — |
| PV2663 | 29/F | GATA2 | GATA2-deficiency syndrome | ICUS | Hashimoto thyroiditis and papillary carcinoma; chronic gastritis; obesity; early menarche | Paternal aunt with breast cancer and paternal grandfather with esophagus cancer; maternal grandmother with pancreatic cancer | — |
| PV2274 | 23/F | GATA2 | GATA2-deficiency syndrome | AML | Long-lasting peripheral blood cytopenia; recurrent respiratory infections | — | — |
| PV1264 | 24/F | GATA2 | GATA2-deficiency syndrome | MDS-MLD | — | Grandfather with multiple myeloma | — |
| PV2661 | 45/M | NF1 | NF | CMML-0 | Moderate-to-severe cognitive deficit, aortic stenosis and hypertension, short stature; GIST in imatinib therapy | — | — |
| PV2662 | 44/F | PTPN11 | NS | ICUS | Short stature, amenorrhea since age 25, hepatic fibrosis, portal hypertension and esophageal varices | — | — |
| PV2664 | 38/M | RPS26 | DBA | ICUS | Steroid diabetes | Paternal grandmother died of lung cancer | — |
| PV1774 | 52/F | RUNX1∗ | RUNX1-related FPD | MDS/MPN-U | Essential tremor since age 29; low count platelets since 1985 | Brother with CMML; cousin died of leukemia | Father died of lung fibrosis |
| PV2117 | 24/F |
SBDS∗ SBDS∗ |
SDS | ICUS | Short stature, intellectual disability/low IQ; pancreatic insufficiency; knee chondropathy | — | Brother with isolated neutropenia |
ALL, acute lymphoblastic leukemia; APCAs, antiparietal cell antibodies; CMML, chronic myelomonocytic leukemia; DBA, Diamond-Blackfan anemia; F, female; FA, Fanconi anemia; FPD, familial platelet disorder; GIST, gastrointestinal stromal tumor; ID, identification number; M, male; MDS-EB, MDS with excess blasts; MDS-MLD, myelodysplastic syndrome with multilineage dysplasia; MDS/MPN-U, MDS/myeloproliferative neoplasm unclassifiable; NF, neurofibromatosis; NS, Noonan syndrome; SDS, Shwachman-Diamond syndrome; SCN, severe congenital neutropenia.
The same FANCA variant was detected in heterozygosity in the son who was not affected. The same GATA1 variant was detected in a sister with primary myelofibrosis. The same RUNX1 variant was detected in the brother affected with CMML. Both SBDS variants were detected in the brother with isolated neutropenia.