MCID: MCR359
MIFTS: 41

Macrothrombocytopenia and Granulocyte Inclusions with or Without Nephritis or Sensorineural Hearing Loss

Categories: Genetic diseases, Ear diseases, Blood diseases

Aliases & Classifications for Macrothrombocytopenia and Granulocyte Inclusions with or Without...

MalaCards integrated aliases for Macrothrombocytopenia and Granulocyte Inclusions with or Without Nephritis or Sensorineural Hearing Loss:

Name: Macrothrombocytopenia and Granulocyte Inclusions with or Without Nephritis or Sensorineural Hearing Loss 57
Fechtner Syndrome 57 76 75 37 29 13 55 6 40 73
Sebastian Syndrome 57 75 37 29 13 55 6 40 73
May-Hegglin Anomaly 57 75 37 29 13 55 6 40
Epstein Syndrome 57 75 37 29 13 6 40 73
Macrothrombocytopenia and Progressive Sensorineural Deafness 57 75 29 13 6 40
Macrothrombocytopenia with Leukocyte Inclusions 57 76 75
Dohle Leukocyte Inclusions with Giant Platelets 57 75
Bdplt6 57 75
Epstns 57 75
Ftns 57 75
Mha 57 75
Sbs 57 75
Macrothrombocytopenia, Nephritis, Deafness, and Leukocyte Inclusions 57
Alport Syndrome with Macrothrombocytopenia, Formerly; Apsm, Formerly 57
Macrothrombocytopenia with Dispersed Leukocytic Inclusions 57
Alport Syndrome with Macrothrombocytopenia, Formerly 57
Macrothrombocytopenia, Nephritis, and Deafness 57
Giant Platelet Syndrome with Thrombocytopenia 57
Bleeding Disorder, Platelet-Type, 6; Bdplt6 57
Macrothrombocytopathy-Nephritis-Deafness 75
Bleeding Disorder, Platelet-Type, 6 57
Bleeding Disorder Platelet-Type 6 75
Sebastian Platelet Syndrome 57
May-Hegglin Anomaly; Mha 57
Epstein Syndrome; Epstns 57
Sebastian Syndrome; Sbs 57
Fechtner Syndrome; Ftns 57
Epsteins Syndrome 55
Apsm, Formerly 57
Matins 57
Mpsd 75

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
most common inherited giant platelet disorder


HPO:

32
macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Macrothrombocytopenia and Granulocyte Inclusions with or Without...

OMIM : 57 Macrothrombocytopenia with or without granulocyte inclusions, nephritis, or sensorineural hearing loss was previously thought to be comprised of 4 distinct entities with overlapping features: Fechtner syndrome, May-Hegglin anomaly, Epstein syndrome, and Sebastian syndrome. Fechtner syndrome was characterized by the triad of thrombocytopenia, giant platelets, and Dohle body-like inclusions in peripheral blood leukocytes, with the additional Alport syndrome (301050)-like features of nephritis, hearing loss, and eye abnormalities, predominantly cataracts (Peterson et al., 1985). May-Hegglin anomaly was characterized by the triad of thrombocytopenia, giant platelets, and Dohle body-like inclusions in peripheral blood leukocytes. Epstein syndrome was characterized by thrombocytopenia, deafness, and nephritis, and lacked leukocyte inclusion bodies on classic staining of peripheral blood smears. Sebastian syndrome was similar to May-Hegglin anomaly, but had a different ultrastructural appearance of the leukocyte inclusions. Seri et al. (2003) suggested that these 4 disorders were not distinct entities, but rather represented a single disorder with a continuous clinical spectrum because variable phenotypic expression is observed not only between families but also within families having the same MYH9 mutation. In addition, Balduini et al. (2011) noted that all patients present leukocyte inclusion bodies, although of variable size. Seri et al. (2003) proposed the term 'MYH9-related disease' for the disorder; however, an isolated form of nonsyndromic deafness (DFNA17; 603622) is also caused by mutation in the MYH9 gene. (155100)

MalaCards based summary : Macrothrombocytopenia and Granulocyte Inclusions with or Without Nephritis or Sensorineural Hearing Loss, also known as fechtner syndrome, is related to sick building syndrome and myh9 related thrombocytopenia. An important gene associated with Macrothrombocytopenia and Granulocyte Inclusions with or Without Nephritis or Sensorineural Hearing Loss is MYH9 (Myosin Heavy Chain 9), and among its related pathways/superpathways are Tight junction and Regulation of actin cytoskeleton. Affiliated tissues include eye, kidney and neutrophil, and related phenotypes are bruising susceptibility and thrombocytopenia

UniProtKB/Swiss-Prot : 75 Epstein syndrome: An autosomal dominant disorder characterized by the association of macrothrombocytopathy, sensorineural hearing loss and nephritis. Fechtner syndrome: Autosomal dominant macrothrombocytopenia characterized by thrombocytopenia, giant platelets and leukocyte inclusions that are small and poorly organized. Additionally, FTNS is distinguished by Alport-like clinical features of sensorineural deafness, cataracts and nephritis. Macrothrombocytopenia and progressive sensorineural deafness: An autosomal dominant disorder characterized by the association of macrothrombocytopathy and progressive sensorineural hearing loss without renal dysfunction. May-Hegglin anomaly: A disorder characterized by thrombocytopenia, giant platelets and Dohle body-like inclusions in peripheral blood leukocytes. appearing as highly parallel paracrystalline bodies. Sebastian syndrome: Autosomal dominant macrothrombocytopenia characterized by thrombocytopenia, giant platelets and leukocyte inclusions that are smaller and less organized than in May-Hegglin anomaly.

Wikipedia : 76 Fechtner syndrome is a variant of Alport syndrome characterized by leukocyte inclusions,... more...

Related Diseases for Macrothrombocytopenia and Granulocyte Inclusions with or Without...

Diseases related to Macrothrombocytopenia and Granulocyte Inclusions with or Without Nephritis or Sensorineural Hearing Loss via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 29)
# Related Disease Score Top Affiliating Genes
1 sick building syndrome 11.4
2 myh9 related thrombocytopenia 11.4
3 alport syndrome, autosomal dominant 11.3
4 short bowel syndrome 11.3
5 macrothrombocytopenia progressive deafness 11.3
6 neural tube defects 11.3
7 brooke-spiegler syndrome 11.2
8 bernard-soulier syndrome 11.0
9 congenital short bowel syndrome 10.9
10 autosomal dominant macrothrombocytopenia 10.2
11 thrombocytopenia 10.1
12 myh-9 related disease 10.1
13 thrombocytopenic purpura, autoimmune 10.0
14 stroke, ischemic 10.0
15 thrombosis 10.0
16 coronary thrombosis 10.0
17 glossitis 10.0
18 pharyngitis 10.0
19 purpura 10.0
20 cerebritis 10.0
21 hypotonia 10.0
22 asthma 9.9
23 shaken baby syndrome 9.9
24 breast cancer 9.7
25 anxiety 9.7
26 acute lymphocytic leukemia 9.7
27 leukemia 9.7
28 venous insufficiency 9.7
29 allergic asthma 9.7

Graphical network of the top 20 diseases related to Macrothrombocytopenia and Granulocyte Inclusions with or Without Nephritis or Sensorineural Hearing Loss:



Diseases related to Macrothrombocytopenia and Granulocyte Inclusions with or Without Nephritis or Sensorineural Hearing Loss

Symptoms & Phenotypes for Macrothrombocytopenia and Granulocyte Inclusions with or Without...

Symptoms via clinical synopsis from OMIM:

57
Hematology:
thrombocytopenia
giant platelets
mild-significant bleeding episodes (epistaxis, easy bruisability, postoperative hemorrhage, menorrhagia)
sky-blue leukocyte inclusion bodies (dohle-like bodies) that contain clusters of ribosomes oriented along parallel microfilaments

Cardiovascular Heart:
myocardial infarction (secondary to coronary artery thrombosis)

Laboratory Abnormalities:
prolonged bleeding time
thrombocytopenia, mild-moderate (60-100 x 10(9)/l)
median mean platelet volume (mpv) 12.5fl
normal platelet aggregation response to epinephrine, adp, collagen, and ristocetin

Genitourinary Kidneys:
no kidney disease


Clinical features from OMIM:

155100

Human phenotypes related to Macrothrombocytopenia and Granulocyte Inclusions with or Without Nephritis or Sensorineural Hearing Loss:

32 (show all 22)
# Description HPO Frequency HPO Source Accession
1 bruising susceptibility 32 HP:0000978
2 thrombocytopenia 32 HP:0001873
3 giant platelets 32 HP:0001902
4 gastrointestinal hemorrhage 32 HP:0002239
5 prolonged bleeding after dental extraction 32 HP:0006298
6 proteinuria 32 HP:0000093
7 nephritis 32 HP:0000123
8 menorrhagia 32 HP:0000132
9 congenital cataract 32 HP:0000519
10 hematuria 32 HP:0000790
11 high-frequency sensorineural hearing impairment 32 very rare (1%) HP:0001757
12 prolonged bleeding time 32 HP:0003010
13 stage 5 chronic kidney disease 32 HP:0003774
14 neutrophil inclusion bodies 32 HP:0008264
15 leukocyte inclusion bodies 32 HP:0040235
16 epistaxis 32 HP:0000421
17 cataract 32 HP:0000518
18 hypertension 32 HP:0000822
19 microscopic hematuria 32 HP:0002907
20 bilateral sensorineural hearing impairment 32 very rare (1%) HP:0008619
21 myocardial infarction 32 HP:0001658
22 abnormal thrombosis 32 HP:0001977

Drugs & Therapeutics for Macrothrombocytopenia and Granulocyte Inclusions with or Without...

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Efficacy of Eltrombopag to Improve Thrombocytopenia of MYH9-related Disease Completed NCT01133860 Phase 2 eltrombopag
2 Eltrombopag for Inherited Thrombocytopenias Active, not recruiting NCT02422394 Phase 2 Eltrombopag
3 Phenotypic and Genotypic Identification and Characterization of MYH9-related Constitutional Thrombocytopenia Completed NCT00925236

Search NIH Clinical Center for Macrothrombocytopenia and Granulocyte Inclusions with or Without Nephritis or Sensorineural Hearing Loss

Genetic Tests for Macrothrombocytopenia and Granulocyte Inclusions with or Without...

Genetic tests related to Macrothrombocytopenia and Granulocyte Inclusions with or Without Nephritis or Sensorineural Hearing Loss:

# Genetic test Affiliating Genes
1 May-Hegglin Anomaly 29 MYH9
2 Fechtner Syndrome 29 MYH9
3 Epstein Syndrome 29 MYH9
4 Sebastian Syndrome 29
5 Macrothrombocytopenia and Progressive Sensorineural Deafness 29

Anatomical Context for Macrothrombocytopenia and Granulocyte Inclusions with or Without...

MalaCards organs/tissues related to Macrothrombocytopenia and Granulocyte Inclusions with or Without Nephritis or Sensorineural Hearing Loss:

41
Eye, Kidney, Neutrophil

Publications for Macrothrombocytopenia and Granulocyte Inclusions with or Without...

Articles related to Macrothrombocytopenia and Granulocyte Inclusions with or Without Nephritis or Sensorineural Hearing Loss:

(show all 24)
# Title Authors Year
1
A patient with Fechtner syndrome successfully treated with romiplostim. ( 22273764 )
2012
2
[Fechtner syndrome, a nonmuscle myosin heavy chain 9 gene mutation related disease: a case report and literature review]. ( 21429376 )
2011
3
Fechtner syndrome--a myosin heavy chain 9 disorder--and pregnancy. ( 20178880 )
2010
4
Patients with Epstein-Fechtner syndromes owing to MYH9 R702 mutations develop progressive proteinuric renal disease. ( 20200500 )
2010
5
[Expression and function of non-muscle myosin-IIA in Fechtner syndrome]. ( 18718080 )
2008
6
Perioperative management of MYH9 hereditary macrothrombocytopenia (Fechtner syndrome). ( 17655694 )
2007
7
Overexpressed platelet integrin alphaIIbbeta3 in a Fechtner syndrome patient uneventfully undergoing adenotomy. ( 17205288 )
2007
8
[Clinical and molecular study on Fechtner syndrome--case report and literature review]. ( 17649707 )
2007
9
MYH9-related disease: may-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. ( 12792306 )
2003
10
Asp1424Asn MYH9 mutation results in an unstable protein responsible for the phenotypes in May-Hegglin anomaly/Fechtner syndrome. ( 12649151 )
2003
11
Genetics, clinical and pathological features of glomerulonephritis associated with mutations of nonmuscle myosin IIA (Fechtner syndrome). ( 12500226 )
2003
12
Expression of the nonmuscle myosin heavy chain IIA in the human kidney and screening for MYH9 mutations in Epstein and Fechtner syndromes. ( 11752022 )
2002
13
Mutations in human nonmuscle myosin IIA found in patients with May-Hegglin anomaly and Fechtner syndrome result in impaired enzymatic function. ( 12237319 )
2002
14
Perioperative management of a patient with Fechtner syndrome. ( 11529472 )
2001
15
Localisation of the gene responsible for fechtner syndrome in a region <600 Kb on 22q11-q13. ( 11093280 )
2000
16
A pregnancy complicated with Fechtner syndrome: a case report. ( 10997559 )
2000
17
Fechtner syndrome: physiologic analysis of macrothrombocytopenia. ( 10870804 )
2000
18
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. ( 11071640 )
2000
19
End-stage renal disease in two pediatric patients with Fechtner syndrome. ( 10603121 )
1999
20
Genetic linkage of autosomal-dominant Alport syndrome with leukocyte inclusions and macrothrombocytopenia (Fechtner syndrome) to chromosome 22q11-13. ( 10577925 )
1999
21
Fechtner syndrome variant: a new family with mild Alport's manifestations. ( 8043458 )
1994
22
Fechtner syndrome: report of a third family and literature review. ( 8280620 )
1993
23
Fechtner syndrome: clinical and genetic aspects. ( 3232700 )
1988
24
Fechtner syndrome--a variant of Alport's syndrome with leukocyte inclusions and macrothrombocytopenia. ( 2981587 )
1985

Variations for Macrothrombocytopenia and Granulocyte Inclusions with or Without...

UniProtKB/Swiss-Prot genetic disease variations for Macrothrombocytopenia and Granulocyte Inclusions with or Without Nephritis or Sensorineural Hearing Loss:

75
# Symbol AA change Variation ID SNP ID
1 MYH9 p.Asn93Lys VAR_010791 rs121913655
2 MYH9 p.Arg702Cys VAR_010792 rs80338826
3 MYH9 p.Thr1155Ile VAR_010794 rs121913656
4 MYH9 p.Asp1424His VAR_010796 rs80338831
5 MYH9 p.Glu1841Lys VAR_010797 rs80338834
6 MYH9 p.Ala95Thr VAR_018308
7 MYH9 p.Lys373Asn VAR_018310
8 MYH9 p.Arg1165Leu VAR_018313 rs80338830
9 MYH9 p.Asp1424Asn VAR_018316 rs80338831
10 MYH9 p.Asp1424Tyr VAR_018317 rs80338831

ClinVar genetic disease variations for Macrothrombocytopenia and Granulocyte Inclusions with or Without Nephritis or Sensorineural Hearing Loss:

6
(show all 35)
# Gene Variation Type Significance SNP ID Assembly Location
1 MYH9 NM_002473.5(MYH9): c.5797C> T (p.Arg1933Ter) single nucleotide variant Pathogenic rs80338835 GRCh37 Chromosome 22, 36678800: 36678800
2 MYH9 NM_002473.5(MYH9): c.5797C> T (p.Arg1933Ter) single nucleotide variant Pathogenic rs80338835 GRCh38 Chromosome 22, 36282754: 36282754
3 MYH9 NM_002473.5(MYH9): c.5521G> A (p.Glu1841Lys) single nucleotide variant Pathogenic rs80338834 GRCh37 Chromosome 22, 36680520: 36680520
4 MYH9 NM_002473.5(MYH9): c.5521G> A (p.Glu1841Lys) single nucleotide variant Pathogenic rs80338834 GRCh38 Chromosome 22, 36284474: 36284474
5 MYH9 NM_002473.5(MYH9): c.3493C> T (p.Arg1165Cys) single nucleotide variant Pathogenic rs80338829 GRCh37 Chromosome 22, 36691115: 36691115
6 MYH9 NM_002473.5(MYH9): c.3493C> T (p.Arg1165Cys) single nucleotide variant Pathogenic rs80338829 GRCh38 Chromosome 22, 36295069: 36295069
7 MYH9 NM_002473.5(MYH9): c.279C> G (p.Asn93Lys) single nucleotide variant Pathogenic rs121913655 GRCh37 Chromosome 22, 36745003: 36745003
8 MYH9 NM_002473.5(MYH9): c.279C> G (p.Asn93Lys) single nucleotide variant Pathogenic rs121913655 GRCh38 Chromosome 22, 36348958: 36348958
9 MYH9 NM_002473.5(MYH9): c.4270G> C (p.Asp1424His) single nucleotide variant Pathogenic rs80338831 GRCh37 Chromosome 22, 36688106: 36688106
10 MYH9 NM_002473.5(MYH9): c.4270G> C (p.Asp1424His) single nucleotide variant Pathogenic rs80338831 GRCh38 Chromosome 22, 36292060: 36292060
11 MYH9 NM_002473.5(MYH9): c.3464C> T (p.Thr1155Ile) single nucleotide variant Pathogenic rs121913656 GRCh37 Chromosome 22, 36691572: 36691572
12 MYH9 NM_002473.5(MYH9): c.3464C> T (p.Thr1155Ile) single nucleotide variant Pathogenic rs121913656 GRCh38 Chromosome 22, 36295526: 36295526
13 MYH9 NM_002473.5(MYH9): c.2104C> T (p.Arg702Cys) single nucleotide variant Pathogenic rs80338826 GRCh37 Chromosome 22, 36702031: 36702031
14 MYH9 NM_002473.5(MYH9): c.2104C> T (p.Arg702Cys) single nucleotide variant Pathogenic rs80338826 GRCh38 Chromosome 22, 36305985: 36305985
15 MYH9 NM_002473.5(MYH9): c.5821delG (p.Asp1941Metfs) deletion Pathogenic rs587776808 GRCh37 Chromosome 22, 36678776: 36678776
16 MYH9 NM_002473.5(MYH9): c.5821delG (p.Asp1941Metfs) deletion Pathogenic rs587776808 GRCh38 Chromosome 22, 36282730: 36282730
17 MYH9 NM_002473.5(MYH9): c.2105G> A (p.Arg702His) single nucleotide variant Pathogenic rs80338827 GRCh37 Chromosome 22, 36702030: 36702030
18 MYH9 NM_002473.5(MYH9): c.2105G> A (p.Arg702His) single nucleotide variant Pathogenic rs80338827 GRCh38 Chromosome 22, 36305984: 36305984
19 MYH9 NM_002473.5(MYH9): c.4270G> A (p.Asp1424Asn) single nucleotide variant Pathogenic rs80338831 GRCh37 Chromosome 22, 36688106: 36688106
20 MYH9 NM_002473.5(MYH9): c.4270G> A (p.Asp1424Asn) single nucleotide variant Pathogenic rs80338831 GRCh38 Chromosome 22, 36292060: 36292060
21 MYH9 NM_002473.5(MYH9): c.287C> T (p.Ser96Leu) single nucleotide variant Pathogenic rs121913657 GRCh37 Chromosome 22, 36744995: 36744995
22 MYH9 NM_002473.5(MYH9): c.287C> T (p.Ser96Leu) single nucleotide variant Pathogenic rs121913657 GRCh38 Chromosome 22, 36348950: 36348950
23 MYH9 NM_002473.5(MYH9): c.3195_3215del21 (p.Gln1068_Leu1074del) deletion Pathogenic rs876661302 GRCh37 Chromosome 22, 36692946: 36692966
24 MYH9 NM_002473.5(MYH9): c.3195_3215del21 (p.Gln1068_Leu1074del) deletion Pathogenic rs876661302 GRCh38 Chromosome 22, 36296900: 36296920
25 MYH9 NM_002473.5(MYH9) duplication Pathogenic rs876661303 GRCh37 Chromosome 22, 36692946: 36692966
26 MYH9 NM_002473.5(MYH9) duplication Pathogenic rs876661303 GRCh38 Chromosome 22, 36296900: 36296920
27 MYH9 MYH9, 18-BP DEL, NT228 deletion Pathogenic
28 MYH9 NM_002473.5(MYH9): c.136C> T (p.Leu46Phe) single nucleotide variant Benign/Likely benign rs147122501 GRCh37 Chromosome 22, 36745146: 36745146
29 MYH9 NM_002473.5(MYH9): c.136C> T (p.Leu46Phe) single nucleotide variant Benign/Likely benign rs147122501 GRCh38 Chromosome 22, 36349101: 36349101
30 MYH9 NM_002473.5(MYH9): c.5275-7_5275-5delTCT deletion Uncertain significance rs780656298 GRCh37 Chromosome 22, 36681380: 36681382
31 MYH9 NM_002473.5(MYH9): c.5275-7_5275-5delTCT deletion Uncertain significance rs780656298 GRCh38 Chromosome 22, 36285334: 36285336
32 MYH9 NM_002473.5(MYH9): c.5563C> T (p.Arg1855Trp) single nucleotide variant not provided GRCh38 Chromosome 22, 36284432: 36284432
33 MYH9 NM_002473.5(MYH9): c.5563C> T (p.Arg1855Trp) single nucleotide variant not provided GRCh37 Chromosome 22, 36680478: 36680478
34 MYH9 NM_002473.5(MYH9): c.658G> A (p.Ala220Thr) single nucleotide variant Uncertain significance GRCh38 Chromosome 22, 36322476: 36322476
35 MYH9 NM_002473.5(MYH9): c.658G> A (p.Ala220Thr) single nucleotide variant Uncertain significance GRCh37 Chromosome 22, 36718521: 36718521

Expression for Macrothrombocytopenia and Granulocyte Inclusions with or Without...

Search GEO for disease gene expression data for Macrothrombocytopenia and Granulocyte Inclusions with or Without Nephritis or Sensorineural Hearing Loss.

Pathways for Macrothrombocytopenia and Granulocyte Inclusions with or Without...

Pathways related to Macrothrombocytopenia and Granulocyte Inclusions with or Without Nephritis or Sensorineural Hearing Loss according to KEGG:

37
# Name Kegg Source Accession
1 Tight junction hsa04530
2 Regulation of actin cytoskeleton hsa04810

GO Terms for Macrothrombocytopenia and Granulocyte Inclusions with or Without...

Sources for Macrothrombocytopenia and Granulocyte Inclusions with or Without...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
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36 IUPHAR
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38 LifeMap
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44 MeSH
45 MESH via Orphanet
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49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
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74 UMLS via Orphanet
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