Table 1.

The known familial MDS/AL predisposition syndromes

Name of syndrome	Causative gene(s)	Pattern of inheritance	Characteristic hematopoietic malignancies	Other hematopoietic abnormalities	Susceptibility to other malignancies	Other associated syndromes/phenotypic findings	Initial diagnosis in childhood or adulthood	CLIA- approved testing available	Recommended diagnostic clinical test	References
Familial platelet disorder with propensity to myeloid malignancies (OMIM 601399)	RUNX1	AD	MDS/AML/T-cell ALL	Lifelong thrombocytopenia (mild-moderate); Bleeding propensity due to aspirin-like platelet dysfunction	None	None	Both	Yes	Full gene sequencing and rearrangement testing of RUNX1	1, 4, 12, 38
Familial AML with mutated CEBPA (OMIM 116897)	CEBPA	AD	AML	Eosinophilia	None	None	Both	Yes	Full gene sequencing of CEBPA	18–20, 24
Familial MDS/AML with mutated GATA2 (OMIM 137295)	GATA2	AD	MDS/AML	None**	None	Emberger Syndrome: primary lymphedema, immunodeficiency, cutaneous warts, sensorineural deafness MonoMAC syndrome: pulmonary alveolar proteinosis, monocytopenia, NK cell, dendritic cell, and B cell lymphopenia, disseminated atypical mycobacterial/viral/fungal infections	Both	Yes	Full gene sequencing and rearrangement testing of GATA2	26–29
Telomere biology disorders due to mutation in TERC or TERT (OMIM 127550)	TERC TERT	AD AD*	MDS/AML	Macrocytosis Mild to moderate single or multiple cytopenias Aplastic anemia	Squamous cell carcinomas of the head/neck and anogenital regions	Autosomal dominant TBD: Idiopathic pulmonary fibrosis, idiopathic hepatic cirrhosis Autosomal recessive or X-linked recessive TBD: nail dystrophy, oral leukoplakia, skin hypo- or hyperpigmentation, premature gray hair, dental caries, hepatic cirrhosis, pulmonary fibrosis; Severe AR forms: cerebellar hypoplasia, immunodeficiency, developmental delay	Both	Yes	Initial diagnostic test: Telomere length studies of lymphocyte subsets via FlowFISH; If abnormal: Full gene sequencing of TERT and TERC	5, 14–16

^*Also has an autosomal recessive form with a more severe clinical presentation including mucocutaneous findings.

^**The described families with familial MDS/AML with mutated GATA2 did not have preceding hematopoietic abnormalities, but given the overlap with Emberger and MonoMAC syndromes as well as identification of GATA2 mutations among those with congenital neutropenia, it is likely possible to find some of the hematopoietic deficits described in these syndromes also featuring GATA2 mutations such as neutropenia, monocytopenia, NK cell, dendritic cell, and B cell deficiencies.

AD, autosomal dominant.