Table 1.

Genes associated with IPDs

Inherited conditionGene (location)InheritanceKey features
Microthrombocytic    
 Wiskott-Aldrich syndrome WAS (Xp11) X-linked Thrombocytopenia, eczema, severe immunodeficiency, small platelets 
 X-linked thrombocytopenia WAS (Xp11-exon2) X-linked Small platelets, thrombocytopenia, mild immunodeficiency 
 FYB-related thrombocytopenia FYB (5p13.1) AR Small platelets and mild to moderate bleeding 
 ARCP1B-related thrombocytopenia ARCP1B(7q22.1) AR Microthrombocytopenia, eosinophilia, inflammatory disease 
Normothrombocytic    
 Congenital amegakaryocytic thrombocytopenia MPL (1p34) AR Hypomegakaryocytic thrombocytopenia with eventual development of bone marrow failure 
 Thrombocytopenia with absent radii RBM8A (1q21.1) AR Thrombocytopenia that improves with age, limb anomalies (normal thumbs) 
 Radio-ulnar synostosis with amegakaryocytic thrombocytopenia HOXA11 (7p15), MECOM (3q26.2) AD Severe thrombocytopenia that improves with age, skeletal abnormalities (radio-ulnar synostosis, clinodactyly, syndactyly, hip dysplasia), hearing loss 
 Familial platelet disorder with predisposition to AML RUNX1 (21q22) AD Thrombocytopenia, myelodysplasia or AML, platelet dysfunction 
 Paris-Trousseau/Jacobsen syndrome FLI1 (11p24.3) AR Thrombocytopenia with large granules and, depending on size of deletion, other symptoms arising from deletion of other genes 
 Familial thrombocytopenia 2 ANKRD26 (10p12.1) AD Mild to moderate thrombocytopenia with mild bleeding symptoms, cancer predisposition with risk of myeloid malignancy and MDS 
 ETV6-related thrombocytopenia ETV6 (12p13.2) AD Mild to moderate thrombocytopenia, increased risk of hematologic malignancy, including ALL, AML, and MDS 
 Monoallelic THPO mutation THPO (3q27.1) AD Minimal to no bleeding with low platelet count 
 CYCS-related thrombocytopenia CYCS (7p15) AD Thrombocytopenia without significant bleeding due to abnormal platelet release 
Macrothrombocytic    
 Bernard-Soulier syndrome GPIBA (17p13), GPIBB (22q11), GPIX (3q21) AR, AD Platelet dysfunction with large platelets 
 Velocardiofacial syndrome 22q11 AD Cardiac anomalies, cleft palate, hypocalcemia, thymic aplasia, and typical facies. BSS-like thrombocytopenia with or without autoimmune etiology 
 Platelet-type von Willebrand disease GPIBA (17p13) AD Decreased high molecular weight VWF multimers with thrombocytopenia (increased platelet affinity for VWF) 
 MYH9-related disease MYH9 (22q11.2) AD Large platelets, leukocyte inclusions; may have sensorineural hearing loss, cataracts, glomerulonephritis, or renal failure 
 Gray platelet syndrome NBEAL2 (3p21) AD, AR Large, pale platelets with absence of α granules 
 GATA-1 mutation of X-linked thrombocytopenia with thalassemia GATA1 (Xp11.23) X-linked Thrombocytopenia with variable anemia 
 SLFN14-related thrombocytopenia SLFN14 (17q12) AD Variable platelet size with mild to severe bleeding and impaired platelet function 
 Stormorken syndrome/York platelet syndrome STIM1 (11p15) or ORAI1 (12q24.31) AD Tubular aggregate myopathy and platelet disorder with decreased α granules, thrombocytopenia, abnormal function, and mild to moderate bleeding 
 TUBB1-related thrombocytopenia TUBB1 (20q13.32) AD Spherocytic platelets and decreased cardiovascular disease in males 
 Macrothrombocytopenia with filamin A mutations FLNA (Xq28) X-Linked Abnormal granule distribution on EM, mild to moderate thrombocytopenia, impaired aggregation to collagen 
 GFI1b-related thrombocytopenia GFI1b (9q24) AD Moderate to severe bleeding with gray platelet-like phenotype with absent α granules and variable red cell anisocytosis 
 TRPM7-related thrombocytopenia TRPM7 (15q21.2) AD Large platelets with aberrant granule distribution and mild bleeding 
 ACTN1-related thrombocytopenia ACTN1 (14q24) AD Large platelets with absent to mild bleeding 
 PRKACG-related thrombocytopenia PRKACG (9q21) AR Large platelets with aberrant FLNA expression and impaired function 
 TPM4-related thrombocytopenia TPM4 (19p13.1) AD Large platelets with mild bleeding 
 DIAPH1-related thrombocytopenia DIAPH1 (5q31.3) AD Sensorineural hearing loss, large platelets 
 SRC-related thrombocytopenia SRC (20q11.23) AD Moderate to severe bleeding with hypogranular platelets and impaired platelet function and juvenile onset myelofibrosis, osteoporosis 
 ITGA2B/ITGB3-related thrombocytopenia ITGA2B (17q21) or ITGB3 (17q21) AD Moderate bleeding, large platelets, and abnormal function with gain-of-function variants 
Inherited conditionGene (location)InheritanceKey features
Microthrombocytic    
 Wiskott-Aldrich syndrome WAS (Xp11) X-linked Thrombocytopenia, eczema, severe immunodeficiency, small platelets 
 X-linked thrombocytopenia WAS (Xp11-exon2) X-linked Small platelets, thrombocytopenia, mild immunodeficiency 
 FYB-related thrombocytopenia FYB (5p13.1) AR Small platelets and mild to moderate bleeding 
 ARCP1B-related thrombocytopenia ARCP1B(7q22.1) AR Microthrombocytopenia, eosinophilia, inflammatory disease 
Normothrombocytic    
 Congenital amegakaryocytic thrombocytopenia MPL (1p34) AR Hypomegakaryocytic thrombocytopenia with eventual development of bone marrow failure 
 Thrombocytopenia with absent radii RBM8A (1q21.1) AR Thrombocytopenia that improves with age, limb anomalies (normal thumbs) 
 Radio-ulnar synostosis with amegakaryocytic thrombocytopenia HOXA11 (7p15), MECOM (3q26.2) AD Severe thrombocytopenia that improves with age, skeletal abnormalities (radio-ulnar synostosis, clinodactyly, syndactyly, hip dysplasia), hearing loss 
 Familial platelet disorder with predisposition to AML RUNX1 (21q22) AD Thrombocytopenia, myelodysplasia or AML, platelet dysfunction 
 Paris-Trousseau/Jacobsen syndrome FLI1 (11p24.3) AR Thrombocytopenia with large granules and, depending on size of deletion, other symptoms arising from deletion of other genes 
 Familial thrombocytopenia 2 ANKRD26 (10p12.1) AD Mild to moderate thrombocytopenia with mild bleeding symptoms, cancer predisposition with risk of myeloid malignancy and MDS 
 ETV6-related thrombocytopenia ETV6 (12p13.2) AD Mild to moderate thrombocytopenia, increased risk of hematologic malignancy, including ALL, AML, and MDS 
 Monoallelic THPO mutation THPO (3q27.1) AD Minimal to no bleeding with low platelet count 
 CYCS-related thrombocytopenia CYCS (7p15) AD Thrombocytopenia without significant bleeding due to abnormal platelet release 
Macrothrombocytic    
 Bernard-Soulier syndrome GPIBA (17p13), GPIBB (22q11), GPIX (3q21) AR, AD Platelet dysfunction with large platelets 
 Velocardiofacial syndrome 22q11 AD Cardiac anomalies, cleft palate, hypocalcemia, thymic aplasia, and typical facies. BSS-like thrombocytopenia with or without autoimmune etiology 
 Platelet-type von Willebrand disease GPIBA (17p13) AD Decreased high molecular weight VWF multimers with thrombocytopenia (increased platelet affinity for VWF) 
 MYH9-related disease MYH9 (22q11.2) AD Large platelets, leukocyte inclusions; may have sensorineural hearing loss, cataracts, glomerulonephritis, or renal failure 
 Gray platelet syndrome NBEAL2 (3p21) AD, AR Large, pale platelets with absence of α granules 
 GATA-1 mutation of X-linked thrombocytopenia with thalassemia GATA1 (Xp11.23) X-linked Thrombocytopenia with variable anemia 
 SLFN14-related thrombocytopenia SLFN14 (17q12) AD Variable platelet size with mild to severe bleeding and impaired platelet function 
 Stormorken syndrome/York platelet syndrome STIM1 (11p15) or ORAI1 (12q24.31) AD Tubular aggregate myopathy and platelet disorder with decreased α granules, thrombocytopenia, abnormal function, and mild to moderate bleeding 
 TUBB1-related thrombocytopenia TUBB1 (20q13.32) AD Spherocytic platelets and decreased cardiovascular disease in males 
 Macrothrombocytopenia with filamin A mutations FLNA (Xq28) X-Linked Abnormal granule distribution on EM, mild to moderate thrombocytopenia, impaired aggregation to collagen 
 GFI1b-related thrombocytopenia GFI1b (9q24) AD Moderate to severe bleeding with gray platelet-like phenotype with absent α granules and variable red cell anisocytosis 
 TRPM7-related thrombocytopenia TRPM7 (15q21.2) AD Large platelets with aberrant granule distribution and mild bleeding 
 ACTN1-related thrombocytopenia ACTN1 (14q24) AD Large platelets with absent to mild bleeding 
 PRKACG-related thrombocytopenia PRKACG (9q21) AR Large platelets with aberrant FLNA expression and impaired function 
 TPM4-related thrombocytopenia TPM4 (19p13.1) AD Large platelets with mild bleeding 
 DIAPH1-related thrombocytopenia DIAPH1 (5q31.3) AD Sensorineural hearing loss, large platelets 
 SRC-related thrombocytopenia SRC (20q11.23) AD Moderate to severe bleeding with hypogranular platelets and impaired platelet function and juvenile onset myelofibrosis, osteoporosis 
 ITGA2B/ITGB3-related thrombocytopenia ITGA2B (17q21) or ITGB3 (17q21) AD Moderate bleeding, large platelets, and abnormal function with gain-of-function variants 

Reprinted from Lambert31 with permission.

AD, autosomal dominant; ALL, acute lymphocytic leukemia; AML, acute myeloid leukemia; AR, autosomal recessive; BSS, Bernard-Soulier syndrome; EM, electron microscopy; MDS, myelodysplastic syndrome; VWF, von Willebrand factor.

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