Clinical and hematologic features of DS neonates with silent GATA1 mutations (silent TAM) compared with DS neonates without GATA1 mutations by targeted NGS
| Clinical and hematologic characteristics . | Number (%) of neonates with DS . | ||||
|---|---|---|---|---|---|
| No GATA1 mutations (by targeted NGS) (n = 70) . | Silent TAM (n = 18) . | Silent TAM vs no GATA1 mutations (P value) . | TAM (n = 17) . | Silent TAM vs TAM (P value) . | |
| Gender (male:female) | 30:40 | 10:8 | .4282 | 9:8 | 1.00 |
| Median gestation at birth (wk) | 38.1 | 38.3 | .7122 | 37.0 | .0431 |
| Hepatosplenomegaly | 4 (5.7%) | 0 | .5775 | 7 (341.2%) | .0072 |
| Jaundice | 33 (47.1%) | 11 (61.1%) | .6024 | 13 (76.4%) | .7283 |
| Rash | 1 (1.4%) | 0 | 1.00 | 3 (17.6%) | .2273 |
| Pleural/pericardial effusion and/or ascites | 1 (1.4%) | 0 | 1.00 | 1 (5.9%) | .4848 |
| Congenital heart disease | 37 (52.9%) | 9 (50%) | 1.000 | 8 (47.1%) | .4935 |
| Death | 1 (1.4%) | 1 (5.6%) | .3691 | 0 (0%) | 1.000 |
| ML-DS* | 0 | 1 (5.6%) | .2069 | 3 (17.6%) | .3377 |
| Median follow up (mo) | 34 | 33 | .3587 | 40 | .1043 |
| Hct | 0.592 | 0.617 | .2414 | 0.562 | .0024 |
| Median (range) | (0.243-0.80) | (0.509-0.736) | (0.357-.0.65) | ||
| MCV (fL) | 108.0 | 108.4 | .1715 | 108 | .3777 |
| Median (range) | 88.7-122.1) | (94.4-122.2) | (93.3-133) | ||
| Platelets ×109/L | 166 | 127 | .1840 | 117 | .5274 |
| Median (range) | (26-432) | (50-253) | (36-1208) | ||
| WBC ×109/L | 14.8 | 13.5 | .1074 | 25.8 | <.0001 |
| Median (range) | (4.7-44.2) | (5.5-29.1) | (19.7-73.2) | ||
| Blasts (%) | 4 | 4.5 | .9842 | 35 | <.0001 |
| Median (range) | (0-15) | (1-10) | 15-77) | ||
| Neutrophils ×109/L | 10.58 | 8.5 | .0427 | 13.80 | .0285 |
| Median (range) | (1.5-38.1) | (2.1-23.3) | (7.00-31.00) | ||
| Monocytes ×109/L | 1.19 | 1.10 | .1650 | 1.41 | .1398 |
| Median (range) | (0.38-6.0) | (0.23-2.28) | (0.67-5.28) | ||
| Basophils ×109/L | 0.2 | 0.19 | .6835 | 0.37 | .0197 |
| Median (range) | (0-1.07) | (0-0.6) | (0-1.27) | ||
| Clinical and hematologic characteristics . | Number (%) of neonates with DS . | ||||
|---|---|---|---|---|---|
| No GATA1 mutations (by targeted NGS) (n = 70) . | Silent TAM (n = 18) . | Silent TAM vs no GATA1 mutations (P value) . | TAM (n = 17) . | Silent TAM vs TAM (P value) . | |
| Gender (male:female) | 30:40 | 10:8 | .4282 | 9:8 | 1.00 |
| Median gestation at birth (wk) | 38.1 | 38.3 | .7122 | 37.0 | .0431 |
| Hepatosplenomegaly | 4 (5.7%) | 0 | .5775 | 7 (341.2%) | .0072 |
| Jaundice | 33 (47.1%) | 11 (61.1%) | .6024 | 13 (76.4%) | .7283 |
| Rash | 1 (1.4%) | 0 | 1.00 | 3 (17.6%) | .2273 |
| Pleural/pericardial effusion and/or ascites | 1 (1.4%) | 0 | 1.00 | 1 (5.9%) | .4848 |
| Congenital heart disease | 37 (52.9%) | 9 (50%) | 1.000 | 8 (47.1%) | .4935 |
| Death | 1 (1.4%) | 1 (5.6%) | .3691 | 0 (0%) | 1.000 |
| ML-DS* | 0 | 1 (5.6%) | .2069 | 3 (17.6%) | .3377 |
| Median follow up (mo) | 34 | 33 | .3587 | 40 | .1043 |
| Hct | 0.592 | 0.617 | .2414 | 0.562 | .0024 |
| Median (range) | (0.243-0.80) | (0.509-0.736) | (0.357-.0.65) | ||
| MCV (fL) | 108.0 | 108.4 | .1715 | 108 | .3777 |
| Median (range) | 88.7-122.1) | (94.4-122.2) | (93.3-133) | ||
| Platelets ×109/L | 166 | 127 | .1840 | 117 | .5274 |
| Median (range) | (26-432) | (50-253) | (36-1208) | ||
| WBC ×109/L | 14.8 | 13.5 | .1074 | 25.8 | <.0001 |
| Median (range) | (4.7-44.2) | (5.5-29.1) | (19.7-73.2) | ||
| Blasts (%) | 4 | 4.5 | .9842 | 35 | <.0001 |
| Median (range) | (0-15) | (1-10) | 15-77) | ||
| Neutrophils ×109/L | 10.58 | 8.5 | .0427 | 13.80 | .0285 |
| Median (range) | (1.5-38.1) | (2.1-23.3) | (7.00-31.00) | ||
| Monocytes ×109/L | 1.19 | 1.10 | .1650 | 1.41 | .1398 |
| Median (range) | (0.38-6.0) | (0.23-2.28) | (0.67-5.28) | ||
| Basophils ×109/L | 0.2 | 0.19 | .6835 | 0.37 | .0197 |
| Median (range) | (0-1.07) | (0-0.6) | (0-1.27) | ||
ML-DS was diagnosed in 3 neonates with TAM (DST5, age 2 mo; DST10, age 22 mo; DST12, age 4 mo) and in 1 neonate with silent TAM (DS 108). This neonate had 5% blasts and mild thrombocytopenia at birth (79 × 109/L) but had a normal CBC and smear at age 9 mo. Isolated thrombocytopenia (23 × 109/L) was noted at age 11 mo shortly after a viral illness and was attributed to immune thrombocytopenia (no blasts were seen on the blood smear). Thrombocytopenia persisted, and by age 15 mo occasional blasts were seen on the smear. Progressive pancytopenia led to the diagnosis of ML-DS at age 18 mo (BM blasts 35%; no additional cytogenetic abnormalities). All patients in whom ML-DS developed remain in complete clinical remission after treatment with modified AML chemotherapy.