Table 1.

Comprehensive list of inherited thrombocytopenias

MechanismGeneInheritanceSyndromePlatelet sizeBleedingExtrahematopoietic manifestationsReference
Transcription/splice factors GATA1 X-linked GATA1-associated thrombocytopenia Large or normal Severe Dyserythropoietic anemiaImbalanced globin chain synthesis with normal red cell morphology, splenomegaly 71,72,64,102  
 GFI1B AR/AD GFI1B-related thrombocytopenia Large Severe — 28,29  
 IZKF5 AD IZKF5-related thrombocytopenia Normal  — 46  
 RNU4ATAC AR Roifman syndrome Normal  Growth retardation, skeletal dysplasia, intellectual delay, hypogammaglobulinemia, dysmorphic facial features, retinal dystrophy. Decreased B-cell numbers 97,103  
 RUNX1 AD FPD-PMM Small, normal, or slightly enlarged  Predisposition to leukemia 104–107  
 ETV6 AD — Normal Moderate Predisposition to leukemia 47–50,108  
 FLI1/ del(11q23) AR/AD Paris-Trousseau, Jacobsen Large  Abnormal facial features, cardiac abnormalities, intellectual disability, skin abnormalities.* 32–36  
 HOXA11 AD Radioulnar dysostosis with amegakaryoctic thrombocytopenia Normal Severe Radio-ulnar dysostosis 109  
 MECOM (EVI1) AD Radioulnar dysostosis with amegakaryoctic thrombocytopenia Normal — Radio-ulnar dysostosis, some patients with sensorineural hearing loss, intellectual disability. Some patients without radio-ulnar dysostosis 110–112  
 RBM8A/ del(1q21.1) AR TAR Normal — Skeletal abnormalities (absence of radii, up to absence of upper limbs, can have lower-limb defects) 113,114  
Cytoskeletal TUBB1 AD TUBB1-related thrombocytopenia Large — — 115  
 ACTN1 AD ACTN1-related thrombocytopenia Large — — 116  
 TPM4 AD TPM4-related thrombocytopenia Large — — 117  
 MYH9 AD MYH9-Related disease Giant — Sensorineural hearing loss, kidney disease, cataracts 24  
 DIAPH1 AD DIAPH1-related thrombocytopenia Large — Sensorineural hearing loss 118,119  
 FLNA X-linked FLNA-related thrombocytopenia Large — Variable brain white matter changes, skeletal dysplasia, intellectual disability 120,121  
 CDC42 AD TKS Large — Cardiac defect, developmental delay, dysmorphic facial features, sensorineural hearing loss 122–124  
 WAS X-linked WAS Small — Immunodeficiency, recurrent infections, eczema 125,126  
 WIPF1 AR WAS-like Normal — Immunodeficiency, recurrent infections, eczema 127  
 ARPC1B AR ARCP1B-related thrombocytopenia Small — Poor growth, eosinophilia/inflammatory disease, small vessel vasculitis 100  
 FYB AR CARST Small — Eczema 128  
Signaling PTPRJ AR PTPRJ-related thrombocytopenia Small — — 84  
 GP1BA AR/AD bBSS/mBSS/PTvWD Giant/large/normal — — 129–132  
 GP1BB AR/AD bBSS/mBSS Giant/large — — 133,134  
 GP9 AR BSS Giant — — 135  
 ITGA2B† AD ITGA2B-related thrombocytopenia Large — — 136,137  
 ITGB3† AD ITGB3-related thrombocytopenia Large — — 138–140  
 PRKACG AR PRKACG-related thrombocytopenia Large Severe — 141  
 SLFN14 AD SLFN14-related thrombocytopenia Large Severe — 142  
 ANKRD26 AD ANKRD26-related thrombocytopenia Normal — Predisposition to leukemia 143,144  
 MPL AR CAMT Normal — Progressive bone marrow failure (pancytopenia) 145–147  
 THPO AD THPO-related thrombocytopenia Normal/slightly enlarged — — 148  
Ion channel STIM1 AD Stormorken syndrome N/A — Congenital miosis, tubular myopathy with proximal muscle weakness, ichthyosis 149  
 TRPM7 AD TRPM7-related thrombocytopenia Large — — 150  
Metabolism/mitochondrial ABCG5 AR Sisterolemia Large — Elevated sterols, xanthomas, splenomegaly, stomatocytosis with hemolytic anemia 151–153  
 ABCG8 AR Sisterolemia Large — — 151,153  
 CYCS AD CYSC-related thrombocytopenia Normal/small — — 154  
Sialylation GNE AR GNE-related thrombocytopenia Large — — 155,156  
 SLC35A1 AR SLC35A1-related thrombocytopenia Large — — 157  
 GALE AR GALE-related thrombocytopenia Large Severe Mild anemia or febrile neutropenia present in some 158  
Other NBEAL2 AR GPS Large — Myelofibrosis 25–27  
 MPIG6B AR Congenital macrothrombocytopenia with focal myelofibrosis Large — Myelofibrosis, anemia 159  
 SRC AD SRC-related thrombocytopenia Large — Myelofibrosis, splenomegaly, edentulism, osteoporosis, dysmorphic facial features 30,31  
 KDSR AR KDSR-related thrombocytopenia Large — Keratoderma, ichthyosis 160,161  
MechanismGeneInheritanceSyndromePlatelet sizeBleedingExtrahematopoietic manifestationsReference
Transcription/splice factors GATA1 X-linked GATA1-associated thrombocytopenia Large or normal Severe Dyserythropoietic anemiaImbalanced globin chain synthesis with normal red cell morphology, splenomegaly 71,72,64,102  
 GFI1B AR/AD GFI1B-related thrombocytopenia Large Severe — 28,29  
 IZKF5 AD IZKF5-related thrombocytopenia Normal  — 46  
 RNU4ATAC AR Roifman syndrome Normal  Growth retardation, skeletal dysplasia, intellectual delay, hypogammaglobulinemia, dysmorphic facial features, retinal dystrophy. Decreased B-cell numbers 97,103  
 RUNX1 AD FPD-PMM Small, normal, or slightly enlarged  Predisposition to leukemia 104–107  
 ETV6 AD — Normal Moderate Predisposition to leukemia 47–50,108  
 FLI1/ del(11q23) AR/AD Paris-Trousseau, Jacobsen Large  Abnormal facial features, cardiac abnormalities, intellectual disability, skin abnormalities.* 32–36  
 HOXA11 AD Radioulnar dysostosis with amegakaryoctic thrombocytopenia Normal Severe Radio-ulnar dysostosis 109  
 MECOM (EVI1) AD Radioulnar dysostosis with amegakaryoctic thrombocytopenia Normal — Radio-ulnar dysostosis, some patients with sensorineural hearing loss, intellectual disability. Some patients without radio-ulnar dysostosis 110–112  
 RBM8A/ del(1q21.1) AR TAR Normal — Skeletal abnormalities (absence of radii, up to absence of upper limbs, can have lower-limb defects) 113,114  
Cytoskeletal TUBB1 AD TUBB1-related thrombocytopenia Large — — 115  
 ACTN1 AD ACTN1-related thrombocytopenia Large — — 116  
 TPM4 AD TPM4-related thrombocytopenia Large — — 117  
 MYH9 AD MYH9-Related disease Giant — Sensorineural hearing loss, kidney disease, cataracts 24  
 DIAPH1 AD DIAPH1-related thrombocytopenia Large — Sensorineural hearing loss 118,119  
 FLNA X-linked FLNA-related thrombocytopenia Large — Variable brain white matter changes, skeletal dysplasia, intellectual disability 120,121  
 CDC42 AD TKS Large — Cardiac defect, developmental delay, dysmorphic facial features, sensorineural hearing loss 122–124  
 WAS X-linked WAS Small — Immunodeficiency, recurrent infections, eczema 125,126  
 WIPF1 AR WAS-like Normal — Immunodeficiency, recurrent infections, eczema 127  
 ARPC1B AR ARCP1B-related thrombocytopenia Small — Poor growth, eosinophilia/inflammatory disease, small vessel vasculitis 100  
 FYB AR CARST Small — Eczema 128  
Signaling PTPRJ AR PTPRJ-related thrombocytopenia Small — — 84  
 GP1BA AR/AD bBSS/mBSS/PTvWD Giant/large/normal — — 129–132  
 GP1BB AR/AD bBSS/mBSS Giant/large — — 133,134  
 GP9 AR BSS Giant — — 135  
 ITGA2B† AD ITGA2B-related thrombocytopenia Large — — 136,137  
 ITGB3† AD ITGB3-related thrombocytopenia Large — — 138–140  
 PRKACG AR PRKACG-related thrombocytopenia Large Severe — 141  
 SLFN14 AD SLFN14-related thrombocytopenia Large Severe — 142  
 ANKRD26 AD ANKRD26-related thrombocytopenia Normal — Predisposition to leukemia 143,144  
 MPL AR CAMT Normal — Progressive bone marrow failure (pancytopenia) 145–147  
 THPO AD THPO-related thrombocytopenia Normal/slightly enlarged — — 148  
Ion channel STIM1 AD Stormorken syndrome N/A — Congenital miosis, tubular myopathy with proximal muscle weakness, ichthyosis 149  
 TRPM7 AD TRPM7-related thrombocytopenia Large — — 150  
Metabolism/mitochondrial ABCG5 AR Sisterolemia Large — Elevated sterols, xanthomas, splenomegaly, stomatocytosis with hemolytic anemia 151–153  
 ABCG8 AR Sisterolemia Large — — 151,153  
 CYCS AD CYSC-related thrombocytopenia Normal/small — — 154  
Sialylation GNE AR GNE-related thrombocytopenia Large — — 155,156  
 SLC35A1 AR SLC35A1-related thrombocytopenia Large — — 157  
 GALE AR GALE-related thrombocytopenia Large Severe Mild anemia or febrile neutropenia present in some 158  
Other NBEAL2 AR GPS Large — Myelofibrosis 25–27  
 MPIG6B AR Congenital macrothrombocytopenia with focal myelofibrosis Large — Myelofibrosis, anemia 159  
 SRC AD SRC-related thrombocytopenia Large — Myelofibrosis, splenomegaly, edentulism, osteoporosis, dysmorphic facial features 30,31  
 KDSR AR KDSR-related thrombocytopenia Large — Keratoderma, ichthyosis 160,161  

bBSS, biallelic Bernard-Soulier syndrome; CAMT, congenital amegakaryocytic thrombocytopenia; CARST, congenital autosomal recessive small-platelet thrombocytopenia; FPD-PMM, familial platelet disorder with propensity for myeloid malignancy; GPS, gray platelet syndrome; mBSS, monoallelic Bernard-Soulier syndrome; N/A, information not available; PTVWD, platelet-type von Willebrand disease; TAR, thrombocytopenia absent radii; TKS, Takenouchi-Kosaki syndrome; WAS, Wiskott-Aldrich syndrome; XLT, X-linked thrombocytopenia; XLTT, X-linked thrombocytopenia with thalassemia.

*

FLI1 homozygous missense variant causes thrombocytopenia without the extrahematopoietic features of 11q23 deletion syndrome.33 

†

Variants distinct from those causing classic or variant Glanzmann thrombasthenia.

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