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 IDAge/sexGerm line
mutated gene
Congenital syndrome/disorderDiagnosisExtrahematologic phenotypeFamily history
Hematologic/solid cancerOther
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 
Patient IDAge/sexGerm line
mutated gene
Congenital syndrome/disorderDiagnosisExtrahematologic phenotypeFamily history
Hematologic/solid cancerOther
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.