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Autosomal dominant macrothrombocytopenia

MedGen UID:: 929690
•Concept ID:: C4304021
•: Disease or Syndrome

Synonym:	autosomal dominant macrothrombocytopenia
SNOMED CT:	Autosomal dominant macrothrombocytopenia (720521008)
Modes of inheritance:	Autosomal dominant inheritance MedGen UID: 141047 •Concept ID: C0443147 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Autosomal dominant inheritance (Orphanet)

Monarch Initiative:	MONDO:0015372
Orphanet:	ORPHA140957

Definition

This syndrome has characteristics of congenital thrombocytopenia associated with the presence of large platelets. To date less than 10 cases are reported. The syndrome is caused by mutations in the integrin, beta 3 ITGB3, tubulin, beta-1TUBB1 and actinin, alpha1 ACTN1 genes. These mutations lead to abnormal proplatelets and thrombocytopenia. Transmission is autosomal dominant. [from SNOMEDCT_US]

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVAutosomal dominant macrothrombocytopenia

Isolated hereditary giant platelet disorder
- Autosomal dominant macrothrombocytopenia

Professional guidelines

PubMed

Identification of six novel MYH9 mutations and genotype-phenotype relationships in autosomal dominant macrothrombocytopenia with leukocyte inclusions.

Kunishima S, Matsushita T, Kojima T, Amemiya N, Choi YM, Hosaka N, Inoue M, Jung Y, Mamiya S, Matsumoto K, Miyajima Y, Zhang G, Ruan C, Saito K, Song KS, Yoon HJ, Kamiya T, Saito H
J Hum Genet 2001;46(12):722-9. doi: 10.1007/s100380170007. PMID: 11776386

See all (1)

Recent clinical studies

Etiology

DIAPH1 Mutation as a Novel Cause of Autosomal Dominant Macrothrombocytopenia and Hearing Loss.

Karki NR, Ajebo G, Savage N, Kutlar A
Acta Haematol 2021;144(1):91-94. Epub 2020 Jun 26 doi: 10.1159/000506727. PMID: 32594080

ACTN1 mutations lead to a benign form of platelet macrocytosis not always associated with thrombocytopenia.

Faleschini M, Melazzini F, Marconi C, Giangregorio T, Pippucci T, Cigalini E, Pecci A, Bottega R, Ramenghi U, Siitonen T, Seri M, Pastore A, Savoia A, Noris P
Br J Haematol 2018 Oct;183(2):276-288. Epub 2018 Oct 23 doi: 10.1111/bjh.15531. PMID: 30351444

Eltrombopag to Treat Thrombocytopenia During Last Month of Pregnancy in a Woman With MYH9-Related Disease: A Case Report.

Favier R, De Carne C, Elefant E, Lapusneanu R, Gkalea V, Rigouzzo A
A A Pract 2018 Jan 1;10(1):10-12. doi: 10.1213/XAA.0000000000000621. PMID: 28795988

A missense mutation in the alpha-actinin 1 gene (ACTN1) is the cause of autosomal dominant macrothrombocytopenia in a large French family.

Guéguen P, Rouault K, Chen JM, Raguénès O, Fichou Y, Hardy E, Gobin E, Pan-Petesch B, Kerbiriou M, Trouvé P, Marcorelles P, Abgrall JF, Le Maréchal C, Férec C
PLoS One 2013;8(9):e74728. Epub 2013 Sep 17 doi: 10.1371/journal.pone.0074728. PMID: 24069336 Free PMC Article

Immunofluorescence analysis of neutrophil nonmuscle myosin heavy chain-A in MYH9 disorders: association of subcellular localization with MYH9 mutations.

Kunishima S, Matsushita T, Kojima T, Sako M, Kimura F, Jo EK, Inoue C, Kamiya T, Saito H
Lab Invest 2003 Jan;83(1):115-22. doi: 10.1097/01.lab.0000050960.48774.17. PMID: 12533692

See all (5)

Diagnosis

DIAPH1 Mutation as a Novel Cause of Autosomal Dominant Macrothrombocytopenia and Hearing Loss.

Karki NR, Ajebo G, Savage N, Kutlar A
Acta Haematol 2021;144(1):91-94. Epub 2020 Jun 26 doi: 10.1159/000506727. PMID: 32594080

Rare variants in GP1BB are responsible for autosomal dominant macrothrombocytopenia.

Sivapalaratnam S, Westbury SK, Stephens JC, Greene D, Downes K, Kelly AM, Lentaigne C, Astle WJ, Huizinga EG, Nurden P, Papadia S, Peerlinck K, Penkett CJ, Perry DJ, Roughley C, Simeoni I, Stirrups K, Hart DP, Tait RC, Mumford AD; NIHR BioResource, Laffan MA, Freson K, Ouwehand WH, Kunishima S, Turro E
Blood 2017 Jan 26;129(4):520-524. Epub 2016 Nov 14 doi: 10.1182/blood-2016-08-732248. PMID: 28064200 Free PMC Article

ACTN1 rod domain mutation associated with congenital macrothrombocytopenia.

Yasutomi M, Kunishima S, Okazaki S, Tanizawa A, Tsuchida S, Ohshima Y
Ann Hematol 2016 Jan;95(1):141-144. Epub 2015 Oct 10 doi: 10.1007/s00277-015-2517-6. PMID: 26453073

Sebastian platelet syndrome: a hereditary macrothrombocytopenia.

Rodriguez V, Nichols WL, Charlesworth JE, White JG
Mayo Clin Proc 2003 Nov;78(11):1416-21. doi: 10.4065/78.11.1416. PMID: 14601703

Autosomal dominant macrothrombocytopenia in Italy is most frequently a type of heterozygous Bernard-Soulier syndrome.

Savoia A, Balduini CL, Savino M, Noris P, Del Vecchio M, Perrotta S, Belletti S, Poggi, Iolascon A
Blood 2001 Mar 1;97(5):1330-5. doi: 10.1182/blood.v97.5.1330. PMID: 11222377

See all (9)

Therapy

Eltrombopag to Treat Thrombocytopenia During Last Month of Pregnancy in a Woman With MYH9-Related Disease: A Case Report.

Favier R, De Carne C, Elefant E, Lapusneanu R, Gkalea V, Rigouzzo A
A A Pract 2018 Jan 1;10(1):10-12. doi: 10.1213/XAA.0000000000000621. PMID: 28795988

Acute myeloid leukemia in a child with hereditary thrombocytopenia.

Rheingold SR
Pediatr Blood Cancer 2007 Jan;48(1):105-7. doi: 10.1002/pbc.20677. PMID: 16276527

Sebastian platelet syndrome: a hereditary macrothrombocytopenia.

Rodriguez V, Nichols WL, Charlesworth JE, White JG
Mayo Clin Proc 2003 Nov;78(11):1416-21. doi: 10.4065/78.11.1416. PMID: 14601703

See all (3)

Prognosis

ACTN1 mutations lead to a benign form of platelet macrocytosis not always associated with thrombocytopenia.

Autosomal dominant macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly) is linked to chromosome 22q12-13.

Kelley MJ, Jawien W, Lin A, Hoffmeister K, Pugh EW, Doheny KF, Korczak JF
Hum Genet 2000 May;106(5):557-64. doi: 10.1007/s004390000294. PMID: 10914687

See all (2)

Clinical prediction guides

DIAPH1 Mutation as a Novel Cause of Autosomal Dominant Macrothrombocytopenia and Hearing Loss.

Karki NR, Ajebo G, Savage N, Kutlar A
Acta Haematol 2021;144(1):91-94. Epub 2020 Jun 26 doi: 10.1159/000506727. PMID: 32594080

A missense mutation in the alpha-actinin 1 gene (ACTN1) is the cause of autosomal dominant macrothrombocytopenia in a large French family.

Immunofluorescence analysis of neutrophil nonmuscle myosin heavy chain-A in MYH9 disorders: association of subcellular localization with MYH9 mutations.

Kunishima S, Matsushita T, Kojima T, Sako M, Kimura F, Jo EK, Inoue C, Kamiya T, Saito H
Lab Invest 2003 Jan;83(1):115-22. doi: 10.1097/01.lab.0000050960.48774.17. PMID: 12533692

Autosomal-dominant giant platelet syndromes: a hint of the same genetic defect as in Fechtner syndrome owing to a similar genetic linkage to chromosome 22q11-13.

Toren A, Rozenfeld-Granot G, Rocca B, Epstein CJ, Amariglio N, Laghi F, Landolfi R, Brok-Simoni F, Carlsson LE, Rechavi G, Greinacher A
Blood 2000 Nov 15;96(10):3447-51. PMID: 11071640

Autosomal dominant macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly) is linked to chromosome 22q12-13.

Kelley MJ, Jawien W, Lin A, Hoffmeister K, Pugh EW, Doheny KF, Korczak JF
Hum Genet 2000 May;106(5):557-64. doi: 10.1007/s004390000294. PMID: 10914687

See all (7)

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Autosomal dominant macrothrombocytopenia

Definition

Term Hierarchy

Professional guidelines

PubMed

Recent clinical studies

Etiology

Diagnosis

Therapy

Prognosis

Clinical prediction guides

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