Congenital neutropenia disorders at risk for MDS/AML
| Disease, gene, and inheritance pattern . | Risk of MDS/AML . | Common somatic alterations . | Additional information including nonhematologic features . |
|---|---|---|---|
| ELANE SCN ELANE, AD | 15%-20%51 ; increased incidence of MDS/AML in patients on high doses of G-CSF with poor neutrophil response.54 | CSF3R, RUNX1, ASXL1, SUZ12, EP300, monosomy 7, trisomy 21.75 | Acquired CSF3R mutations common (approximately 50%) in patients without MDS/AML.75 |
| Cyclic neutropenia ELANE, AD | AML rarely reported.76 | CSF3R, monosomy 7, trisomy 21 in the 1 patient with AML.76 | Acquired CSF3R mutations rarely identified in patients without MDS/AML.76 |
| HAX1-SCN HAX1, AR | MDS/AML reported, but incidence of leukemia not precisely reported.77 | Somatic alterations not published. | Acquired CSF3R mutations common (approximately 45%) in patients without MDS/AML.75 |
| G6PC3 deficiency G6PC3, AR | AML rarely reported.78 | T(8;21)(q22;q22) identified by karyotype in one patient.78 | Inflammatory bowel disease, congenital heart and urogenital defects, and endocrine disorders. Acquired CSF3R mutations identified in patients without MDS/AML.75 |
| X-linked neutropenia WAS GOF, XL | MDS/AML rarely reported.79 | Somatic alterations not published. | Acquired CSF3R mutations identified in patients without MDS/AML.75 |
| Glycogen storage disease type 1b G6PT1, AR | 4% with MDS/AML in the SCNIR.80 | Monosomy 7. Short telomeres also reported.81 | Hypoglycemia, hepatomegaly, and enterocolitis. |
| Poikiloderma with neutropenia USB1, AR | MDS/AML reported, but incidence of leukemia not precisely reported.82 Myelodysplastic changes in most patients. | Somatic alterations not published. | Poikiloderma, nail dystrophy, and palmar/plantar hyperkeratosis. |
| SDS SBDS, AR | 20%-30%83,84 ; patients also at risk of BMF.16 | Biallelic TP53, RUNX1, SETBP1, BRAF, NRAS, ETNK1, alterations in chromosomes 3, 5, 7, and 20.85 | Pancreatic exocrine insufficiency, skeletal abnormalities. Somatic alterations not associated with MDS/AML include i(7)(q10), del(20q), and EIF6 mutations. |
| GATA2 haploinsufficiency GATA2, AD | 80%86 ; occurrence typically in later adolescence and early adulthood and may be presenting feature. | Monosomy 7, trisomy 8, ASXL1, der(1;7)(q10;p10).87 | Warts, lymphedema, panniculitis, deafness, infection, and pulmonary alveolar proteinosis. |
| SAMD9/SAMD9L GOF disorder SAMD9 or SAMD9L, AD | Risk of MDS and AML unknown. Patients also at risk of BMF that may spontaneously resolve.88 | Monosomy 7, del(7q), RUNX1, SETBP1, ETV6.89 | SAMD9: adrenal hypoplasia, growth restriction, genital abnormalities, enteropathy, infections. SAMD9L: neurologic symptoms, infections. |
| Disease, gene, and inheritance pattern . | Risk of MDS/AML . | Common somatic alterations . | Additional information including nonhematologic features . |
|---|---|---|---|
| ELANE SCN ELANE, AD | 15%-20%51 ; increased incidence of MDS/AML in patients on high doses of G-CSF with poor neutrophil response.54 | CSF3R, RUNX1, ASXL1, SUZ12, EP300, monosomy 7, trisomy 21.75 | Acquired CSF3R mutations common (approximately 50%) in patients without MDS/AML.75 |
| Cyclic neutropenia ELANE, AD | AML rarely reported.76 | CSF3R, monosomy 7, trisomy 21 in the 1 patient with AML.76 | Acquired CSF3R mutations rarely identified in patients without MDS/AML.76 |
| HAX1-SCN HAX1, AR | MDS/AML reported, but incidence of leukemia not precisely reported.77 | Somatic alterations not published. | Acquired CSF3R mutations common (approximately 45%) in patients without MDS/AML.75 |
| G6PC3 deficiency G6PC3, AR | AML rarely reported.78 | T(8;21)(q22;q22) identified by karyotype in one patient.78 | Inflammatory bowel disease, congenital heart and urogenital defects, and endocrine disorders. Acquired CSF3R mutations identified in patients without MDS/AML.75 |
| X-linked neutropenia WAS GOF, XL | MDS/AML rarely reported.79 | Somatic alterations not published. | Acquired CSF3R mutations identified in patients without MDS/AML.75 |
| Glycogen storage disease type 1b G6PT1, AR | 4% with MDS/AML in the SCNIR.80 | Monosomy 7. Short telomeres also reported.81 | Hypoglycemia, hepatomegaly, and enterocolitis. |
| Poikiloderma with neutropenia USB1, AR | MDS/AML reported, but incidence of leukemia not precisely reported.82 Myelodysplastic changes in most patients. | Somatic alterations not published. | Poikiloderma, nail dystrophy, and palmar/plantar hyperkeratosis. |
| SDS SBDS, AR | 20%-30%83,84 ; patients also at risk of BMF.16 | Biallelic TP53, RUNX1, SETBP1, BRAF, NRAS, ETNK1, alterations in chromosomes 3, 5, 7, and 20.85 | Pancreatic exocrine insufficiency, skeletal abnormalities. Somatic alterations not associated with MDS/AML include i(7)(q10), del(20q), and EIF6 mutations. |
| GATA2 haploinsufficiency GATA2, AD | 80%86 ; occurrence typically in later adolescence and early adulthood and may be presenting feature. | Monosomy 7, trisomy 8, ASXL1, der(1;7)(q10;p10).87 | Warts, lymphedema, panniculitis, deafness, infection, and pulmonary alveolar proteinosis. |
| SAMD9/SAMD9L GOF disorder SAMD9 or SAMD9L, AD | Risk of MDS and AML unknown. Patients also at risk of BMF that may spontaneously resolve.88 | Monosomy 7, del(7q), RUNX1, SETBP1, ETV6.89 | SAMD9: adrenal hypoplasia, growth restriction, genital abnormalities, enteropathy, infections. SAMD9L: neurologic symptoms, infections. |
AD, autosomal dominant; AR, autosomal recessive, GOF, gain of function; XL, X-linked.