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MYH9-Related Disease

, PhD and , MD, PhD.

Author Information and Affiliations

Initial Posting: ; Last Update: February 18, 2021.

Estimated reading time: 33 minutes


Clinical characteristics.

MYH9-related disease (MYH9-RD) is characterized in all affected individuals by hematologic features present from birth consisting of platelet macrocytosis (i.e., >40% of platelets larger than 3.9 μm in diameter), thrombocytopenia (platelet count <150 x 109/L), and aggregates of the MYH9 protein in the cytoplasm of neutrophil granulocytes. Most affected individuals develop one or more additional extrahematologic manifestations of the disease over their lifetime, including sensorineural hearing loss, renal disease (manifesting initially as glomerular nephropathy), presenile cataracts, and/or elevation of liver enzymes.


The diagnosis of MYH9-related disease is established in a proband with suggestive findings and a heterozygous pathogenic variant in MYH9 identified by molecular genetic testing.


Treatment of manifestations: For most active hemorrhages, consider local measures as the first-line treatment; transfusion of platelet concentrates should be used for active hemorrhages that cannot be otherwise managed, life- or organ-threatening hemorrhages, and/or bleeding at critical sites. Whenever necessary, eltrombopag or platelet transfusion should be used to prepare affected individuals for elective surgery. Antifibrinolytic agents and desmopressin are also used for covering hemostatic challenges or treating hemorrhages. Hearing loss, renal complications, and cataracts are managed in a standard fashion; individuals with severe/profound deafness benefit from cochlear implantation.

Surveillance: For individuals with moderate or severe thrombocytopenia: at least annual (and in case of bleeding and/or changes in bleeding diathesis) microscopic assessment of platelet count and blood count to screen for anemia. Screening for individuals not currently under treatment for the following: annually (or every 6 months in individuals with high-risk MYH9 genotypes) for nephropathy, and every three years for hearing loss, cataracts, and abnormal liver enzymes.

Agents/circumstances to avoid: Drugs that inhibit platelet function or reduce platelet count, and drugs that are ototoxic, nephrotoxic, or hepatotoxic should be used only after assessment of risk-to-benefit ratio. Hazardous noise and activities with high risk of injury should be avoided.

Evaluation of relatives at risk: Clarify the status of all first-degree relatives of an affected individual in order to establish appropriate management (including treatment and surveillance) and awareness of agents and circumstances to avoid.

Pregnancy management: Deliveries should be managed as they are in women with other forms of thrombocytopenia; in general, a platelet count of ≥50 x 109/L is recommended for delivery.

Genetic counseling.

MYH9-RD is inherited in an autosomal dominant manner. Approximately 35% of probands represent simplex cases, most of whom have a documented de novo pathogenic variant. Each child of an individual with MYH9-RD has a 50% chance of inheriting the MYH9 pathogenic variant. Once the MYH9 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.

GeneReview Scope

In the past, the phenotypes included in MYH9-related disease (MYH9-RD) were known as Epstein syndrome, Fechtner syndrome, May-Hegglin anomaly, Sebastian syndrome (Sebastian platelet syndrome), and autosomal dominant deafness 17 (DFNA17). The first four phenotypes, all characterized by thrombocytopenia and platelet macrocytosis, were classified on the basis of the presence of Döhle-like bodies and different combinations of the other manifestations of MYH9-RD. DFNA17 was initially described as nonsyndromic deafness, but subsequent investigations showed that this condition is associated with the other manifestations of MYH9-RD. Because the phenotype of a person with an MYH9 pathogenic variant often evolves over time and because the five named phenotypes do not define all the possible manifestations resulting from a heterozygous MYH9 pathogenic variant, MYH9-RD was proposed as a new nosologic entity. The term MYH9-RD encompasses all individuals with a MYH9 pathogenic variant who present typical congenital hematologic features (i.e., macrothrombocytopenia and aggregates of the MYH9 protein in neutrophils) and may develop one or more extrahematologic manifestations of the disease over the course of life.


No consensus clinical diagnostic criteria for MYH9-related disease (MYH9-RD) have been published.

Suggestive Findings

MYH9-RD should be suspected in individuals with the following clinical and laboratory findings and family history.

Clinical findings

  • Manifestations of thrombocytopenia
    • Easy bruising
    • Spontaneous mucocutaneous bleeding
    • Excessive bleeding after hemostatic challenges (major or minor surgery, deliveries, treatment with antiplatelet drugs)
  • Sensorineural hearing loss ranging from a slight defect occurring in the elderly to profound deafness that may manifest at a young age
  • Glomerular nephropathy manifest as proteinuria, with possible evidence of chronic kidney disease
  • Presenile cataract (occurring in early or middle life)

Laboratory findings

  • Platelet abnormalities
    • Thrombocytopenia. Platelet count <150 x 109/L (normal: 150-400 x 109/L)
    • Platelet macrocytosis. Extreme platelet macrocytosis present from birth, a hallmark of MYH9-RD, is a crucial suggestive finding. Mean platelet diameter was 4.5 μm (95% confidence interval, 4.2-4.8) in 125 persons with MYH9-RD compared to 2.6 μm (95% confidence interval, 2.4-2.7) in 55 healthy controls [Noris et al 2014a].
      Giant platelets (i.e., platelets larger than red blood cells) are invariably present on examination of blood smears of persons with MYH9-RD.
      Moreover, a mean platelet diameter >3.7 μm and/or the finding that >40% of platelets are larger than 3.9 µm (i.e., about half the diameter of a red blood cell) has very good sensitivity and specificity in distinguishing MYH9-RD from the other forms of inherited or acquired thrombocytopenia (see Differential Diagnosis) [Noris et al 2014a].
      Note: Electronic cell counters do not recognize the largest platelets of individuals with MYH9-RD, and therefore underestimate both platelet count and size.
  • Neutrophil abnormalities
    • Döhle-like bodies. Faint, slightly basophilic inclusion bodies in the cytoplasm of neutrophils (similar to the Döhle bodies that may be found in persons with an infection) are observed on microscopic assessment of a peripheral blood smear after conventional staining (e.g., May-Grünwald-Giemsa).
      Note: Döhle-like bodies, present in 42%-84% of individuals with MYH9-RD, may escape detection because they can be very faint and/or small [Kunishima et al 2003, Seri et al 2003, Pecci et al 2018].
    • Typical aggregates of the MYH9 protein in the cytoplasm of neutrophils observed on immunofluorescence staining of a peripheral blood smear:
      • Are present at birth and throughout the life span;
      • Can be detected in all individuals with MYH9-RD. For this reason, assay of immunofluorescence staining of MYH9 protein distribution in neutrophils has been validated as a diagnostic test for MYH9-RD with close to 100% specificity and sensitivity [Kunishima et al 2003, Savoia et al 2010, Kitamura et al 2013, Greinacher et al 2017].
        Note: in neutrophils of unaffected individuals, MYH9 protein is uniformly distributed.
  • Elevated liver enzymes (serum alanine aminotransferase and/or aspartate aminotransferase and occasionally serum gamma-glutamyltransferase)

Family history may be consistent with autosomal dominant inheritance (e.g., affected males and females in multiple generations) or the affected individual may represent a simplex case (i.e., a single occurrence in a family). Therefore, absence of a known family history does not preclude the diagnosis.

Establishing the Diagnosis

The diagnosis of MYH9-related disease is established in a proband with suggestive findings and a heterozygous pathogenic variant in MYH9 identified by molecular genetic testing (see Table 1).

Note: Identification of a heterozygous MYH9 variant of uncertain significance does not establish or rule out the diagnosis of this disorder. In these cases, the search for typical aggregates of the MYH9 protein in neutrophils on immunofluorescence staining of blood smears may be a useful tool to assess the pathogenicity of the variant [Greinacher et al 2017].

Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing and multigene panel) and comprehensive genomic testing (exome sequencing and genome sequencing) depending on the phenotype.

Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of MYH9-related disease has not been considered are more likely to be diagnosed using genomic testing (see Option 2).

Option 1

Single-gene testing. Sequence analysis of MYH9 is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications.

A multigene panel that includes MYH9 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.

For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.

Option 2

Comprehensive genomic testing does not require the clinician to determine which gene is likely involved. Exome sequencing is most commonly used; genome sequencing is also possible.

For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.

Table 1.

Molecular Genetic Testing Used in MYH9-Related Disease

Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
MYH9 Sequence analysis 398% 4
Gene-targeted deletion/duplication analysis 5Unknown 6

See Molecular Genetics for information on allelic variants detected in this gene.


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.


The only MYH9 gross deletions/duplications identified to date are deletions/duplications of 21 or 42 bp within exons 21, 24, and 25, which can be detected by sequence analysis. However, because a deletion of 1220 nucleotides with the breakpoints in intron 25 and intron 26 leads to an in-frame removal of exon 26 [Kunishima et al 2008], gene-targeted deletion/duplication analysis may be appropriate in families with a strong clinical history and no identifiable MYH9 pathogenic variant on sequence analysis.

Clinical Characteristics

Clinical Description

MYH9-related disease (MYH9-RD) is characterized in all affected individuals by hematologic features present from birth consisting of platelet macrocytosis (i.e., >40% of platelets >3.9 μm in diameter), thrombocytopenia (platelet count <150 x 109/L), and aggregates of the MYH9 protein in the cytoplasm of neutrophil granulocytes. Most affected individuals develop one or more additional extrahematologic manifestations of the disease over their lifetime, including sensorineural hearing loss, renal disease (manifesting initially as glomerular nephropathy), presenile cataracts, and/or elevation of liver enzymes [Pecci et al 2014a, Pecci et al 2018].

Table 2.

MYH9-Related Disease: Frequency of Select Features

Feature% of Persons
Platelet macrocytosis 100%Present from birth
Thrombocytopenia 98%Present from birth. Very few persons have platelet counts at lower limit of normal range.
Bleeding tendency 80%-90%~30% have spontaneous bleeding. 1 Most persons only have ↑ risk of bleeding secondary to thrombocytopenia after hemostatic challenges.
Sensorineural hearing loss 80%-85%Present in ~50% of persons at mean age of 33 yrs 1 & occurs in most persons over time
Abnormal liver enzymes 50%Develop later in life 2
Nephropathy 25%Mean age at onset: 27 yrs 1
Cataracts 20%Mean age at onset: 37 yrs 1; however, congenital cataracts have been reported.

Platelet macrocytosis is present from birth in all individuals with MYH9-RD (see Diagnosis, Suggestive Findings).

Thrombocytopenia ranges from mild to severe. The degree of thrombocytopenia usually remains stable in each individual throughout life. Because platelet counts at the lower limit of the normal range have been reported in very few individuals with MYH9-RD, platelet macrocytosis and aggregates of the MYH9 protein in neutrophils are the only findings shared among all affected individuals.

Presence and severity of a spontaneous bleeding tendency correlate with the degree of thrombocytopenia. Most affected individuals have no spontaneous bleeding or only easy bruising, and are at risk of significant hemorrhages only after hemostatic challenges. About 30% of persons with MYH9-RD have spontaneous mucocutaneous bleeding – mainly menorrhagia, epistaxis, and gum bleeding [Pecci et al 2014a]. Life-threatening bleeding is rare.

Sensorineural hearing loss is present in about 50% of individuals evaluated at a mean age of 33 years and is expected to occur in most individuals over time [Pecci et al 2014a]. The mean age at onset is 31 years. Onset of hearing loss is distributed evenly from the first to sixth decade. Of those who develop hearing loss, 36% do so before age 20 years, 33% between ages 20 and 40 years, and 31% after age 40 years.

Hearing loss is usually bilateral. Once diagnosed, hearing loss frequently progresses over time, although it can remain stable in a minority of affected individuals. Earlier-onset hearing loss often progresses more rapidly and may result in severe-to-profound deafness [Verver et al 2016].

Hearing loss interferes with activities of daily living in 90% of individuals who have an abnormal audiometric examination [Pecci et al 2014a].

Glomerular nephropathy presents with proteinuria and microhematuria. However, in MYH9-RD, hematuria may result from thrombocytopenia rather than glomerular disease; therefore, proteinuria is the more reliable indicator of glomerular involvement.

The mean age at onset is 27 years. Of those who develop renal disease, 72% are diagnosed before age 35 years. In most individuals with nephropathy, kidney damage is progressive and evolves to end-stage renal disease (ESRD). Among those with nephropathy, the overall annual rate for progression to ESRD is 6.79 per 100 affected persons. After a median follow up of 36 months, 64% of 61 individuals with nephropathy developed chronic kidney disease and 43% developed ESRD [Pecci et al 2014a]. In some cases, kidney damage may appear later in life and/or show a slower progression.

Cataracts. The mean age of onset of cataracts is 37 years, but congenital cataracts have been reported. In most individuals, cataracts are bilateral and progress over time.

Elevated liver enzyme levels. Elevated aspartate aminotransferase and/or alanine aminotransferase (possibly associated with increased gamma-glutamyltransferase) usually remains stable over time. In some affected individuals, normalization of enzyme levels has been observed. Progression to impairment of liver function has not been reported in any affected individual [Pecci et al 2012, Favier et al 2013].

Genotype-Phenotype Correlations

Observed genotype-phenotype correlations are discussed in this section. (See Molecular Genetics, Table 8 for more details.)

Individuals with pathogenic variants involving the head domain of the MYH9 protein have more severe thrombocytopenia compared to those with pathogenic variants affecting the tail domain.

The risk of developing kidney damage, hearing loss, and cataract also depends on the specific MYH9 pathogenic variant [Pecci et al 2014a].

  • Pathogenic variants in the codon for arginine residue 702 (located in the short functional SH1 helix of the head domain) are associated with the most severe phenotype. Individuals with Arg702 substitutions present with severe thrombocytopenia (platelet count usually <50 x 109/L), and all are expected to develop nephropathy and severe hearing loss before age 40 years. Moreover, nephropathy usually progresses rapidly to ESRD in these individuals.
  • The p.Asp1424His substitution is associated with an intermediate-to-high risk of developing extrahematologic manifestations over time. All individuals with this variant are expected to develop hearing loss by age 60 years; most affected individuals develop kidney disease before age 60 years; the risk for cataracts is higher than in those with other genotypes.
  • Pathogenic variants encoding the residues at the interface between the SH3-like motif and the upper 50-kd subdomain of the head domain or those resulting in substitutions of the arginine residue 1165 are associated with a high risk for hearing loss (all are expected to develop hearing loss before age 60 years) and a low risk for nephropathy and cataract.
  • The p.Asp1424Asn and p.Glu1841Lys substitutions, as well as the nonsense or frameshift pathogenic variants resulting in alterations of the carboxy-terminal nonhelical tailpiece of the MYH9 protein, are associated with low risk of developing the manifestations that develop over time; thus, macrothrombocytopenia usually remains the only clinically relevant disease feature throughout life [Pecci et al 2014a].

To date, no significant genotype-phenotype correlations have been identified for the occurrence of elevated liver enzyme levels [Pecci et al 2012].


Penetrance is complete for the following congenital findings:

  • Platelet macrocytosis with giant platelets
  • Aggregates of the MYH9 proteins in neutrophils

Except for a very few individuals in whom platelet count was just above the conventional cut-off value for thrombocytopenia (150 x 109/L), thrombocytopenia is a congenital manifestation of the disease.

Expressivity varies for onset and severity of sensorineural deafness, glomerular nephropathy, presenile cataract, and alterations of liver enzymes.


In the past, the conditions now collectively referred to as MYH9-RD were known as Epstein syndrome, Fechtner syndrome, May-Hegglin anomaly, Sebastian syndrome (Sebastian platelet syndrome), and autosomal dominant deafness 17 (DFNA17). The first four phenotypes, all characterized by macrothrombocytopenia with giant platelets, were classified on the basis of the presence of Döhle-like bodies on conventional staining of blood smears and different combinations of the other manifestations of MYH9-RD (see Table 3). DFNA17 was initially described as a nonsyndromic sensorineural hearing loss deriving from the single NM_002473.5:c.2114G>A (p.Arg705His) pathogenic variant [Lalwani et al 2000] (see also Hereditary Hearing Loss and Deafness Overview). However, subsequent investigations showed that individuals who are heterozygous for the p.Arg705His substitution present other manifestations typical of MYH9-RD along with hearing loss [Saposnik et al 2014, Verver et al 2015].

Table 3.

MYH9-Related Disease: Formerly Used Terminology

Formerly Used Disorder NameClinical Findings
Döhle-like bodiesSNHLCataractNephropathy
Epstein syndrome+++
Fechtner syndrome+++++
May-Hegglin anomaly++
Sebastian syndrome++

Modified from Table 1 in Seri et al [2003]

DFNA17 = autosomal-dominant deafness 17; SNHL = sensorineural hearing loss


MYH9-RD is considered a rare disease. The Italian Registry for MYH9-RD includes 225 Italian affected individuals, indicating that the prevalence of the disorder in Italy is at least 3.75:1,000,000. Because mild forms are often discovered incidentally and severe forms are often misdiagnosed as other disorders, the actual prevalence is expected to be higher. Of note, other estimates – based on the frequency of MYH9 loss-of-function pathogenic variants in the EXAC database– suggest a much higher prevalence (~1:20,000-25,000) [Fernandez-Prado et al 2019].

MYH9-RD has been diagnosed worldwide, and there is no evidence of variation in prevalence across different populations.

Differential Diagnosis

The differential diagnosis of MYH9-related disease (MYH9-RD) should take into consideration acquired and inherited forms of thrombocytopenia as well as collagen IV-related nephropathies.

Acquired Thrombocytopenia

Idiopathic (autoimmune) thrombocytopenic purpura (ITP). Differentiating between MYH9-RD and ITP (the most frequent form of acquired thrombocytopenia) is challenging and individuals with MYH9-RD are frequently misdiagnosed with ITP. Misdiagnosis with ITP often leads to treatments (immunosuppressive drugs and splenectomy) that are not only ineffective in individuals with MYH9-RD but also potentially harmful. For instance, among individuals enrolled in the Italian Registry for MYH9-RD, about 60% of index cases had received a previous diagnosis of ITP and 30% received inappropriate treatments, including splenectomy [Pecci et al 2018].

If the genetic origin of thrombocytopenia is not obvious because a family history is absent or unclear, the following findings on microscopic evaluation of peripheral blood slides are a simple and effective way to distinguish individuals with MYH9-RD from those with ITP [Noris et al 2014a]:

  • Platelets are significantly larger in persons with MYH9-RD than in those with ITP: a mean platelet diameter >3.7 µm distinguishes MYH9-RD from ITP with 86% sensitivity and 87% specificity.
  • More than 40% of platelets >3.9 µm (i.e., about half the diameter of a red blood cell) distinguishes MYH9-RD from ITP with 85% sensitivity and 87% specificity.

Assay of immunofluorescence staining of MYH9 protein distribution in neutrophils can also be used to differentiate MYH9-RD from ITP (see Diagnosis, Suggestive Findings). Molecular genetic testing provides confirmation of the diagnosis of MYH9-RD.

Inherited Thrombocytopenia

Table 4 summarizes the main forms of inherited thrombocytopenia with platelet macrocytosis (inherited macrothrombocytopenias) that should, therefore, be considered in the differential diagnosis of MYH9-RD.

Note: All congenital macrothrombocytopenias are very rare disorders.

Table 4.

Inherited Macrothrombocytopenias in the Differential Diagnosis of MYH9-Related Disease

Gene /
Genetic Mechanism
Diff Dx DisorderMOIAssociated Clinical Characteristics (in addition to macrothrombocytopenia)
11q23 deletionsJacobsen syndrome (OMIM 147791)
Paris-Trousseau thrombocytopenia (OMIM 188025)
ADPhysical growth delay, ID, craniofacial dysmorphism, cryptorchidism, malformations of multiple organs
ACTN1 ACTN1-RT (OMIM 615193)ADNA (nonsyndromic)
CDC42 Takenouchi-Kosaki syndrome w/macrothrombocytopenia (OMIM 616737)ADDefective growth & psychomotor development; ID; facial abnormalities; brain, cardiac, genitourinary, &/or skeletal malformations
DIAPH1 DIAPH1-related disorder (OMIM 124900)ADProgressive sensorineural deafness develops during infancy or childhood.
FLI1 FLI1-RT (OMIM 617443)AD
NA (nonsyndromic)
FLNA FLNA-RT 1XLPeriventricular nodular heterotopia & chronic idiopathic intestinal pseudo-obstruction are assoc in the vast majority of affected persons.
GFI1B GFI1B-RT (OMIM 187900)ADRed-cell anisocytosis or anisopoikilocytosis present in most affected persons
GNE GNE-RT 2ARSkeletal muscle damage reported in some affected persons
Biallelic Bernard-Soulier syndrome (OMIM 231200)ARNA (nonsyndromic); platelets can be as large as in MYH9-RD.
Monoallelic Bernard-Soulier syndrome 3 (OMIM 153670)ADNA (nonsyndromic)
ITGA2B / ITGB3-RT (OMIM 187800)ADNA (nonsyndromic)
NBEAL2 Gray platelet syndrome (OMIM 139090)ARNA (nonsyndromic); hallmark finding is "pale" (gray) platelets on peripheral blood films due to lack of alpha granules.
SLFN14 SLFN14-RT (OMIM 616913)ADNA (nonsyndromic)
SRC SRC-RT (THC6) (OMIM 616937)ADFacial dysmorphism, edentulism, severe osteoporosis, &/or myelofibrosis
TUBB1 TUBB1-RT (OMIM 613112)ADNA (nonsyndromic)

AD = autosomal dominant; AR = autosomal recessive; DiffDx = differential diagnosis; ID = intellectual disability; MOI = mode of inheritance; NA = not applicable; RT = related thrombocytopenia; THC6 = thrombocytopenia 6; XL = X-linked


Hereditary Nephritis

Alport syndrome. The spectrum of renal involvement in Alport syndrome ranges from isolated non-progressive hematuria to progressive nephropathy characterized by hematuria, proteinuria, and chronic kidney disease and end-stage renal disease. Affected individuals often have sensorineural hearing loss and characteristic ocular abnormalities. Rare individuals have associated aortic disease or diffuse leiomyomatosis. Alport syndrome is caused by pathogenic variants in COL4A3, COL4A4, or COL4A5 and can be transmitted in an X-linked, autosomal dominant, or autosomal recessive manner.

Platelet defects have not been described in Alport syndrome. Therefore, whenever nephropathies are associated with macrothrombocytopenia, MYH9-RD should be strongly considered.


No clinical practice guidelines for MYH9-related disease (MYH9-RD) have been published.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with MYH9-RD, the evaluations summarized in Table 5 are recommended at the time of diagnosis.

Table 5.

Recommended Evaluations Following Initial Diagnosis in Individuals with MYH9-Related Disease

Thrombocytopenia Microscopic assessment of platelet countPhase contrast microscopy by counting chamber is most reliable method to assess platelet count in persons w/MYH9-RD (see Diagnosis).
Bleeding episodes
  • Assessment of bleeding history incl spontaneous & provoked bleeding episodes
  • Complete blood count to evaluate for anemia
  • Use of standardized questionnaires (e.g., ISTH Bleeding Assessment Tool 1 ) recommended to obtain bleeding history
  • In persons w/anemia, serum concentration of iron & ferritin to evaluate for iron deficiency
SNHL Screening Audiogram (See Hereditary Hearing Loss and Deafness Overview.)In persons w/severe-to-profound deafness, speech recognition tests
Known Consultation w/audiologist/ otolaryngologist
Nephro-pathy Screening Urinalysis, 24-hour protein, or protein (or albumin) to creatinine ratio on a spot urine sample; serum concentration of creatinine
Known Consultation w/nephrologist
Cataract Ophthalmologic eval incl slit lamp exam
Abnormal liver
Measurement of serum concentration of AST, ALT, & GGT
Genetic counseling By genetics professionals 2To inform affected persons & their families re nature, MOI, & implications of MYH9-RD to facilitate medical & personal decision making
Family support/

ALT = alanine aminotransferase; AST = aspartate aminotransferase; GGT = gamma-glutamyltransferase; ISTH = International Society on Thrombosis and Haemostasis; MOI = mode of inheritance; SNHL = sensorineural hearing loss


Medical geneticist, certified genetic counselor, or certified advanced genetic nurse

Treatment of Manifestations

Multidisciplinary management by different specialists including hematologists or internists with expertise in hemostasis, nephrologists, otolaryngologists, and ophthalmologists is recommended.

Table 6.

Treatment of Manifestations in Individuals with MYH9-Related Disease

cytopenia &
  • Treatments incl local measures, transfusion of platelet concentrates, eltrombopag, antifibrinolytics drugs, desmopressin.
  • Treatments should be administered by hematologist or internist w/expertise in hemostasis.
  • Thrombocytopenia cannot be prevented.
  • Education re drugs that affect platelet function to prevent bleeding (See Agents/Circumstances to Avoid.)
  • Oral contraceptives to prevent or control menorrhagia
  • Regular dental care to prevent gum bleeding
SNHL Education re potentially damaging drugs to prevent occurrence &/or worsening of hearing loss (See Agents/Circumstances to Avoid.)
  • Treatments incl angiotensin converting enzyme inhibitors &/or angiotensin receptor blockers, dialysis, kidney transplantation.
  • Treatments should be administered by nephrologist.
Education re potentially damaging drugs to prevent occurrence &/or worsening of nephropathy (See Agents/Circumstances to Avoid.)
Cataract Cataract surgery, per treating ophthalmologistEducation re drugs predisposing to cataract (See Agents/Circumstances to Avoid.)
liver enzymes
No specific treatmentEducation re potentially hepatotoxic drugs (See Agents/Circumstances to Avoid.)

SNHL = sensorineural hearing loss

Thrombocytopenia and/or Bleeding Tendency

Local measures, the first-line treatment for most mucocutaneous hemorrhages, are often sufficient to control mild or moderate bleeding. Local measures include nasal packing or endoscopic cauterization of the bleeding site for treatment of epistaxis; suturing for hemorrhages from accidental or surgical wounds; and compression and application of gauzes soaked in tranexamic acid for bleeding from superficial wounds. Mouthwash with tranexamic acid may be useful for gingival bleeding.

Transfusions of platelet concentrates are currently used to transiently increase platelet count, and are effective in stopping bleeding episodes; however, they expose treated individuals to the risk of acute reactions, transmission of infectious diseases, and alloimmunization with consequent refractoriness to subsequent platelet transfusions. Thus, platelet transfusions should be limited to treatment for active hemorrhages that cannot be otherwise managed, life- or organ-threatening hemorrhages, and/or bleeding at critical sites. Transfusion of platelet concentrates can also be used as prophylaxis to prepare for hemostatic challenges such as surgery and childbirth. Whenever available, platelets from HLA-matched donors should be used to prevent and/or overcome alloimmunization.

Eltrombopag is an oral drug mimicking the activity of thrombopoietin, the natural hormone that stimulates platelet production. Two prospective Phase II clinical trials showed that a three- to six-week course of eltrombopag is effective in increasing platelet count and reducing/abolishing bleeding tendency in most individuals with MYH9-RD. The first trial tested 12 individuals, of whom 11 showed a response to the drug [Pecci et al 2010]; a more recent trial enrolled nine individuals with MYH9-RD, all of whom responded [Zaninetti et al 2020]. Treatment was well tolerated in both studies.

A recent retrospective case series from a single center reported 11 consecutive surgical procedures in individuals with MYH9-RD, severe thrombocytopenia, and high bleeding risk prepared with eltrombopag administration: in ten, the drug allowed surgery to proceed without bleeding or other complications and without the need for platelet transfusion [Zaninetti et al 2019]. Based on these results, a short-term course of eltrombopag can be used in individuals with MYH9-RD to transiently increase platelet count in preparation for elective surgery or other invasive procedures. Note: At the present time, eltrombopag is approved in the US and Europe only for individuals with some forms of acquired thrombocytopenia or aplastic anemia.

Antifibrinolytic agents. Several authors recommend the systemic administration of antifibrinolytic agents, such as tranexamic or epsilon-aminocaproic acid, to treat mild or moderate mucocutaneous bleeding [Althaus & Greinacher 2009]. Antifibrinolytic drugs are also used empirically as prophylaxis to cover surgery or other hemostatic challenges, especially low-risk procedures, in persons with MYH9-RD [Orsini et al 2017].

Desmopressin (1-deamino-8-D-arginine vasopressin; DDAVP) shortened bleeding time in some individuals with MYH9-RD [Balduini et al 1999]. Successful surgery after prophylaxis with DDAVP has also been reported [Pecci et al 2014b]. However, clinical studies on the efficacy of DDAVP in MYH9-RD are still lacking.

The need for prophylactic intervention in preparation for surgery or other invasive procedures (including platelet transfusion, short-term eltrombopag, and/or empiric use of antifibrinolytics drugs or desmopressin) should be established based on the type of procedure, the individual's previous history of bleeding, and platelet count before the procedure.

Oral contraceptives are often effective in preventing and/or controlling menorrhagia. The risk of thrombosis associated with the administration of oral contraceptives containing estrogens should be taken into account in women with MYH9-RD.

Regular dental care and good oral hygiene are essential to prevent gingival bleeding.

Sensorineural Hearing Loss

Hearing aids are used for individuals with clinically significant hearing loss.

Cochlear implantation. A retrospective analysis of ten individuals and a few case reports indicated that cochlear implantation is effective in restoring hearing function in most persons with MYH9-RD who have severe-to-profound deafness [Pecci et al 2014b, Pecci et al 2018].


Angiotensin converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs). Some retrospective observations indicated that the administration of ACE inhibitors and/or ARBs early during the course of kidney disease may induce the reduction or remission of proteinuria [Pecci et al 2008, Sekine et al 2010], which, in turn, may delay the progression of kidney damage.

Renal replacement therapy (dialysis and kidney transplantation) is the only possible treatment for individuals who develop end-stage renal disease.


Cataract surgery should be carried out when indicated.


Table 7.

Recommended Surveillance for Individuals with MYH9-Related Disease

  • Microscopic assessment of platelet count
  • Note: Electronic cell counters do not recognize the largest platelets of persons w/MYH9-RD & thus underestimate platelet count & size.
At least annually AND in case of bleeding &/or reported changes in bleeding diathesis AND prior to hemostatic challenges (surgery, delivery, other invasive procedures)
Bleeding episodes
  • Assessment of person's bleeding history through standardized questionnaires (e.g., ISTH Bleeding Assessment Tool) 1
  • Blood count to screen for anemia
Annually AND in case of bleeding &/or reported changes in bleeding diathesis AND prior to hemostatic challenges
SNHL Screening AudiogramEvery 3 yrs AND in case of reported worsening of hearing function
Known Per treating audiologist/ otolaryngologistPer treating audiologist/ otolaryngologist
Screening Urinalysis, 24-hour protein, or protein (or albumin)-to-creatinine ratio on a spot urine sample; serum concentration of creatinineAnnually, or every 6 mos in genotypes w/high risk of kidney damage (See Genotype/Phenotype Correlations.)
Known Per treating nephrologistPer treating nephrologist
Cataract Screening Ophthalmologic exam incl slit lampEvery 3 yrs AND in case of reported symptoms suggestive for cataract
Known Per treating ophthalmologistPer treating ophthalmologist
Abnormal liver enzymes Measurement of serum AST, ALT, & GGTEvery 3 yrs
If other causes of liver damage are excluded when liver enzymes are alteredFrequency of liver enzyme measurements depends on severity of alteration.

ALT = alanine aminotransferase; AST = aspartate aminotransferase; GGT = gamma-glutamyltransferase; ISTH = International Society on Thrombosis and Haemostasis; SNHL = sensorineural hearing loss


Agents/Circumstances to Avoid

Bleeding Tendency

Agents. Drugs that can inhibit platelet function or reduce platelet count should be administered only after a careful assessment of the risks versus the benefits. Patients and treating physicians should be informed about such drugs.

  • Drugs that inhibit platelet function include:
    • Nonsteroidal anti-inflammatory drugs, especially aspirin, which are strong inhibitors of platelet aggregation;
    • Other drugs that interfere with platelet function, including some antidepressants, antibiotics, and anesthetics.
  • Drugs that may reduce platelet count include oncologic treatments and some antibiotics.

Antithrombotic drugs (such as heparin or oral anticoagulants) should be prescribed with caution and after a careful assessment of the risk-to-benefit ratio, as in patients affected with other forms of thrombocytopenia. MYH9 pathogenic variants are usually not associated with defects of platelet function, and therefore platelet function is usually normal in patients with MYH9-RD.

Circumstances. In individuals with severe thrombocytopenia and significant bleeding tendency, activities at high risk of trauma (e.g., contact sports) should be avoided.

Hearing Loss

Agents. Ototoxic drugs (e.g., aminoglycoside antibiotics, salicylates in large quantities, loop diuretics, some oncologic drugs) should be used only after a careful assessment of the risks versus the benefits, especially in patients with established hearing involvement or with MYH9 pathogenic variants associated with high risk of hearing loss (see Genotype-Phenotype Correlations).

Circumstances. Avoid exposure to hazardous noise. If noise exposure cannot be avoided, use ear devices (e.g., earplugs, headphones) to attenuate intense sound.


Agents. The balance between the risks and the benefits of agents that can damage renal function, including radiographic contrast agents, antibiotics, NSAIDs, diuretics, and oncologic drugs, should be carefully considered, especially in individuals with established kidney involvement or with MYH9 pathogenic variants associated with high risk of kidney damage (see Genotype-Phenotype Correlations).


Agents. Glucocorticoids, which predispose to development of cataracts, should be used only after a careful assessment of the risk-to-benefit ratio.

Elevation of Liver Enzymes

Agents. In individuals with MYH9-RD who have liver enzyme elevation, potentially hepatotoxic drugs should be used with caution.

Evaluation of Relatives at Risk

It is appropriate to clarify the status of all first-degree relatives of an affected individual in order to establish: (1) appropriate management (including follow-up evaluations, treatment, and surveillance) and (2) awareness of agents and circumstances that should be avoided.

Evaluations to clarify the status of at-risk family members include:

  • Examination of peripheral blood smear to search for platelet macrocytosis, assessment of platelet count, and immunofluorescence search for aggregates of the MYH9 protein;
  • Molecular genetic testing if the MYH9 pathogenic variant has been identified in an affected family member.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

Deliveries should be managed as they are in women with other forms of thrombocytopenia. (Note that MYH9-RD is not usually associated with defects of platelet function.) As expected, severe thrombocytopenia and previous history of severe bleeding are associated with a higher incidence of delivery-related bleeding. In general, a platelet count of ≥50 x 109/L is recommended for delivery. Infants born vaginally to women with severe thrombocytopenia are considered at increased risk for neonatal intracranial bleeding [Noris et al 2014b].

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members; it is not meant to address all personal, cultural, or ethical issues that may arise or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

MYH9-related disease (MYH9-RD) is inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

  • Approximately 65% of probands diagnosed with MYH9-RD have an affected parent.
  • An individual with MYH9-RD may have the disorder as the result of a de novo MYH9 pathogenic variant. About 35% of probands represent simplex cases (i.e., a single occurrence in a family) [Savoia et al 2010]; most of these individuals have the disorder as the result of a de novo pathogenic variant [Pecci et al 2108].
  • If neither parent of the proband is known to have MYH9-RD, the following evaluations are recommended for the parents in order to confirm their status and to allow reliable recurrence risk counseling:
  • If the pathogenic variant found in the proband is not identified in either parent, the following possibilities should be considered:
  • The family history of some individuals diagnosed with MYH9-RD may appear to be negative because of failure to recognize the disorder in family members and/or a milder phenotypic presentation. Therefore, an apparently negative family history cannot be confirmed unless molecular genetic testing has demonstrated that neither parent is heterozygous for the pathogenic variant identified in the proband and/or appropriate hematologic testing has been performed.

Sibs of a proband. The risk to the sibs of the proband depends on the genetic status of the proband’s parents:

Offspring of a proband. Each child of an individual with MYH9-RD has a 50% chance of inheriting the MYH9 pathogenic variant.

Other family members. The risk to other family members depends on the status of the proband's parents: if a parent has the MYH9 pathogenic variant and/or is known to be affected, his or her family members may be at risk.

Related Genetic Counseling Issues

See Management, Evaluation of Relatives at Risk for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing and Preimplantation Genetic Testing

Once the MYH9 pathogenic variant has been identified in an affected family member, prenatal testing and preimplantation genetic testing are possible.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.


GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • American Society for Deaf Children
    Phone: 800-942-2732 (ASDC)
    Email: info@deafchildren.org
  • MedlinePlus
  • National Association of the Deaf
    Phone: 301-587-1788 (Purple/ZVRS); 301-328-1443 (Sorenson); 301-338-6380 (Convo)
    Fax: 301-587-1791
    Email: nad.info@nad.org
  • National Eye Institute
    31 Center Drive
    MSC 2510
    Bethesda MD 20892-2510
  • National Kidney Foundation
    Phone: 855-NKF-CARES; 855-653-2273
    Email: nkfcares@kidney.org
  • Platelet Disorder Support Association
    Phone: 877-528-3538
    Email: pdsa@pdsa.org
  • Italian Registry of MYH9-Related Disease
    Clinica Medica III IRCCS Policlinico
    San Matteo Foundation
    Piazzale Golgi, 2
    Pavia 27100
    Phone: +39 0382.526284; +39 0382 501358
    Fax: +39 0382 526223
    Email: alessandro.pecci@unipv.it

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

MYH9-Related Disease: Genes and Databases

GeneChromosome LocusProteinLocus-Specific DatabasesHGMDClinVar
MYH9 22q12​.3 Myosin-9 Hereditary Hearing Loss Homepage (MYH9)
MYH9 database

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for MYH9-Related Disease (View All in OMIM)


Molecular Pathogenesis

MYH9 encodes myosin-9, a protein of 1960 amino acids also known as the heavy chain of the non-muscle myosin IIA. Myosin-9 dimerizes and assembles with two essential and two regulatory light chains to constitute a hexameric molecule, the non-muscle myosin IIA (NMMIIA). NMMIIA assembles into functional bipolar filaments, which – interacting with actin – generate the mechanical force necessary for a variety of cellular processes, including motility and migration, cytokinesis, shape maintenance and change, and polarization.

Pathogenesis of the manifestations of MYH9-related disease is only partially understood. Macrothrombocytopenia results from defective production of platelets from megakaryocytes, their bone marrow precursors. In particular, the platelet phenotypes result from defects of the latest events of platelet biogenesis – that is, the formation and release of platelets from mature megakaryocytes. At the end of their maturation process, megakaryocytes form platelets through the extension of long and thin cellular protrusions, called proplatelets, that protrude through the lumen of bone marrow vessels and release platelets directly into the bloodstream from their free ends (the so-called tips).

NMMIIA is dispensable for megakaryocyte production and maturation, but has a key role in the extension of proplatelets. In fact, megakaryocytes of individuals with MYH9-RD, as well as those of mouse models of the disease, present few proplatelets, with reduced branching and very large tips, resulting in defective platelet release as well as platelet macrocytosis [Pecci et al 2018]. Moreover, MYH9 pathogenic variants may also impair migration of megakaryocytes within the bone marrow toward the marrow vessels, the site of platelet release; this mechanism can contribute to reduced platelet production [Pal et al 2020].

Kidney damage is thought to mainly result from defective function of the podocytes, highly specialized epithelial cells of the renal glomerular filtration barrier. Investigations of mouse models of MYH9-RD showed signs of podocyte damage, such as effacement of their foot processes with loss of the filtration slit between neighboring foot processes. These alterations resemble those observed in the few kidney biopsies of individuals with MYH9-RD analyzed to date. Moreover, in vitro studies demonstrated that MYH9 pathogenic variants induce profound alteration in the structure and functions of the cytoskeleton of podocytes that are likely to cause alteration of the kidney filtration barrier, proteinuria, and, therefore, progressive kidney disease [Pecci et al 2018].

The mechanisms of hearing loss are poorly understood. However, the hearing defect is likely to derive from alteration of the functions of the hair cells of the cochlea of the inner ear – that is, the cells specialized in converting the sound stimulus into electric signals directed to the brain.

Pathogenesis of the other phenotypes of MYH9-RD is unknown [Pecci et al 2018].

Mechanism of disease causation. Because MYH9-RD is an autosomal dominant disorder and myosin consists of dimerization of two MYH9 protein molecules, the pathogenic mechanisms are likely to be associated with a dominant-negative effect of the pathogenic variants.

MYH9-specific laboratory technical considerations. MYH9 comprises 41 exons. The first exon does not code for amino acids; the first methionine of the open reading frame is in exon 2. Exon numbering may vary among different testing laboratories.

The spectrum of the MYH9 pathogenic variants responsible for MYH9-related disease is mainly represented by missense variants or small in-frame deletions/insertions, most of which are identified in a few hot spots (exons 2, 17, 25, 26, 27, 31, and 39). The nonsense and frameshift pathogenic variants affect exclusively the last coding exon of MYH9 (exon 41).

Moreover, almost 70% of affected individuals have pathogenic variants involving only six residues: Ser96 or Arg702 of the head domain; and Arg1165, Asp1424, Glu1841, or Arg1933 of the tail domain [Pecci et al 2018].

Table 8.

Notable MYH9 Pathogenic Variants

Reference SequencesDNA
MYH9 ProteinComment [Reference]
c.279C>Gp.Asn93LysHeadSH3/MD i
c.287C>Tp.Ser96LeuHeadSH3/MD i
c.2104C>Tp.Arg702CysHeadSH1 helixAssoc w/most severe phenotype 1
c.2105G>Ap.Arg702HisHeadSH1 helix
c.3493C>Tp.Arg1165CysTailCoiled-coilAssoc w/high risk for hearing loss & low risk for nephropathy & cataract 1
c.4270G>Cp.Asp1424HisTailCoiled-coilAssoc w/intermediate-to-high risk of developing disease manifestations over time 1
c.4270G>Ap.Asp1424AsnTailCoiled-coilAssoc w/thrombocytopenia, but low risk of developing other disease manifestations over time 1
c.5521G>Ap.Glu1841LysTailCoiled-coilAssoc w/thrombocytopenia, but low risk of developing other disease manifestations over time 1
c.5797C>Tp.Arg1933TerTailNHTThrombocytopenia usually remains only disease manifestation throughout life 1 [Pecci et al 2014a].

NHT = nonhelical tailpiece; SH3/MD i = interface between the SH3-like motif and the motor domain

Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​.hgvs.org). See Quick Reference for an explanation of nomenclature.


Chapter Notes

Author Notes

Alessandro Pecci works as a physician and researcher at the IRCCS Policlinico San Matteo Foundation and the University of Pavia, Pavia, Italy. His research interests focus on hemostasis and thrombosis, ranging from clinical to basic research. He is particularly interested in clinical aspects, management and pathogenetic mechanisms of inherited thrombocytopenias. Email: ti.vpinu@iccep.ordnassela

Author History

Carlo L Balduini, MD; University of Pavia (2008-2015)
Alessandro Pecci, MD, PhD (2015-present)
Anna Savoia, PhD (2008-present)

Revision History

  • 18 February 2021 (bp) Comprehensive update posted live
  • 16 July 2015 (me) Comprehensive update posted live
  • 5 April 2011 (me) Comprehensive update posted live
  • 25 June 2009 (cd) Revision: deletion/duplication analysis available clinically
  • 20 November 2008 (me) Review posted live
  • 9 July 2008 (as) Original submission


Literature Cited

  • Althaus K, Greinacher A. MYH9-related platelet disorders. Semin Thromb Hemost. 2009;35:189–203. [PubMed: 19408192]
  • Balduini CL, Noris P, Belletti S, Spedini P, Gamba G. In vitro and in vivo effects of desmopressin on platelet function. Haematologica. 1999;84:891–6. [PubMed: 10509036]
  • Favier R, DiFeo A, Hezard N, Fabre M, Bedossa P, Martignetti JA. A new feature of the MYH9-related syndrome: chronic transaminase elevation. Hepatology. 2013;57:1288–9. [PubMed: 22806255]
  • Fernandez-Prado R, Carriazo-Julio SM, Torra R, Ortiz A, Perez-Gomez MV. MYH9-related disease: it does exist, may be more frequent than you think and requires specific therapy. Clin Kidney J. 2019;12:488–93. [PMC free article: PMC6671427] [PubMed: 31384439]
  • Fewings E, Ziemer M, Hörtnagel K, Reicherter K, Larionov A, Redman J, Goldgraben MA, Pepler A, Hearn T, Firth H, Ha T, Schaller J, Adams DJ, Rytina E, van Steensel M, Tischkowitz M. Malta (MYH9 associated elastin aggregation) syndrome: germline variants in MYH9 cause rare sweat duct proliferations and irregular elastin ggregations. J Invest Dermatol. 2019;139:2238–2241.e6. [PubMed: 31125547]
  • Futterer J, Dalby A, Lowe GC, Johnson B, Simpson MA, Motwani J, Williams M, Watson SP, Morgan NV, et al. Mutation in GNE is associated with severe congenital thrombocytopenia. Blood. 2018;132:1855–8. [PMC free article: PMC6238157] [PubMed: 29941673]
  • Greinacher A, Pecci A, Kunishima S, Althaus K, Nurden P, Balduini CL, Bakchoul T. Diagnosis of inherited platelet disorders on a blood smear: a tool to facilitate worldwide diagnosis of platelet disorders. J Thromb Haemost. 2017;15:1511–21. [PubMed: 28457011]
  • Gresele P, De Rocco D, Bury L, Fierro T, Mezzasoma AM, Pecci A, Savoia A. Apparent genotype-phenotype mismatch in a patient with MYH9-related disease: when the exception proves the rule. Thromb Haemost. 2013;110:618–20. [PubMed: 23925420]
  • Gresele P, Orsini S, Noris P, Falcinelli E, Alessi MC, Bury L, Borhany M, Santoro C, Glembotsky AC, Cid AR, Tosetto A, De Candia E, Fontana P, Guglielmini G, Pecci A, et al. Validation of the ISTH/SSC bleeding assessment tool for inherited platelet disorders: a communication from the Platelet Physiology SSC. J Thromb Haemost. 2020;18:732–39. [PubMed: 31750621]
  • Kitamura K, Yoshida K, Shiraishi Y, Chiba K, Tanaka H, Furukawa K, Miyano S, Ogawa S, Kunishima S. Normal neutrophil myosin IIA localization in an immunofluorescence analysis can rule out MYH9 disorders. J Thromb Haemost. 2013;11:2071–3. [PubMed: 24106837]
  • Kunishima S, Kitamura K, Matsumoto T, Sekine T, Saito H. Somatic mosaicism in MYH9 disorders: the need to carefully evaluate apparently healthy parents. Br J Haematol. 2014;165:885–7. [PubMed: 24611568]
  • Kunishima S, Matsushita T, Hamaguchi M, Saito H. Identification and characterization of the first large deletion of the MYH9 gene associated with MYH9 disorders. Eur J Haematol. 2008;80:540–4. [PubMed: 18284620]
  • Kunishima S, Matsushita T, Kojima T, Sako M, Kimura F, Jo EK, Inoue C, Kamiya T, Saito H. Immunofluorescence analysis of neutrophil nonmuscle myosin heavy chain-A (NMMHCA) in MYH9 disorders: association of subcellular localization with MYH9 mutations. Lab Invest. 2003;83:115–22. [PubMed: 12533692]
  • Kunishima S, Matsushita T, Yoshihara T, Nakase Y, Yokoi K, Hamaguchi M, Saito H. First description of somatic mosaicism in MYH9 disorders. Br J Haematol. 2005;128:360–5. [PubMed: 15667538]
  • Kunishima S, Takaki K, Ito Y, Saito H. Germinal mosaicism in MYH9 disorders: a family with two affected siblings of normal parents. Br J Haematol. 2009;145:260–2. [PubMed: 19208103]
  • Lalwani AK, Goldstein JA, Kelley MJ, Luxford W, Castelein CM, Mhatre AN. Human nonsyndromic hereditary deafness DFNA17 is due to a mutation in nonmuscle myosin MYH9. Am J Hum Genet. 2000;67:1121–8. [PMC free article: PMC1288554] [PubMed: 11023810]
  • Noris P, Biino G, Pecci A, Civaschi E, Savoia A, Seri M, Melazzini F, Loffredo G, Russo G, Bozzi V, Notarangelo LD, Gresele P, Heller PG, Pujol-Moix N, Kunishima S, Cattaneo M, Bussel J, De Candia E, Cagioni C, Ramenghi U, Barozzi S, Fabris F, Balduini CL. Platelet diameters in inherited thrombocytopenias: analysis of 376 patients with all known disorders. Blood. 2014a;124:e4–e10. [PMC free article: PMC4126341] [PubMed: 24990887]
  • Noris P, Schlegel N, Klersy C, Heller PG, Civaschi E, Pujol-Moix N, Fabris F, Favier R, Gresele P, Latger-Cannard V, Cuker A, Nurden P, Greinacher A, Cattaneo M, De Candia E, Pecci A, Hurtaud-Roux MF, Glembotsky AC, Muñiz-Diaz E, Randi ML, Trillot N, Bury L, Lecompte T, Marconi C, Savoia A, Balduini CL, Bayart S, Bauters A, Benabdallah-Guedira S, Boehlen F, Borg JY, Bottega R, Bussel J, De Rocco D, de Maistre E, Faleschini M, Falcinelli E, Ferrari S, Ferster A, Fierro T, Fleury D, Fontana P, James C, Lanza F, Le Cam Duchez V, Loffredo G, Magini P, Martin-Coignard D, Menard F, Mercier S, Mezzasoma A, Minuz P, Nichele I, Notarangelo LD, Pippucci T, Podda GM, Pouymayou C, Rigouzzo A, Royer B, Sie P, Siguret V, Trichet C, Tucci A, Saposnik B, Veneri D, et al. Analysis of 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Haematologica. 2014b;99:1387–94. [PMC free article: PMC4116839] [PubMed: 24763399]
  • Orsini S, Noris P, Bury L, Heller PG, Santoro C, Kadir RA, Butta NC, Falcinelli E, Cid AR, Fabris F, Fouassier M, Miyazaki K, Lozano ML, Zúñiga P, Flaujac C, Podda GM, Bermejo N, Favier R, Henskens Y, De Maistre E, De Candia E, Mumford AD, Ozdemir GN, Eker I, Nurden P, Bayart S, Lambert MP, Bussel J, Zieger B, Tosetto A, Melazzini F, Glembotsky AC, Pecci A, Cattaneo M, Schlegel N, Gresele P, et al. Bleeding risk of surgery and its prevention in patients with inherited platelet disorders. Haematologica. 2017;102:1192–1203. [PMC free article: PMC5566025] [PubMed: 28385783]
  • Pal K, Nowak R, Billington N, Liu R, Ghosh A, Sellers JR, Fowler VM. Megakaryocyte migration defects due to nonmuscle myosin IIA mutations underlie thrombocytopenia in MYH9-related disease. Blood. 2020;135:1887–98. [PMC free article: PMC7243143] [PubMed: 32315395]
  • Pecci A, Biino G, Fierro T, Bozzi V, Mezzasoma A, Noris P, Ramenghi U, Loffredo G, Fabris F, Momi S, Magrini U, Pirastu M, Savoia A, Balduini C, Gresele P, et al. Alteration of liver enzymes is a feature of the MYH9-related disease syndrome. PLoS One. 2012;7:e35986. [PMC free article: PMC3338476] [PubMed: 22558294]
  • Pecci A, Granata A, Fiore CE, Balduini CL. Renin-angiotensin system blockade is effective in reducing proteinuria of individuals with progressive nephropathy caused by MYH9 mutations (Fechtner-Epstein syndrome). Nephrol Dial Transplant. 2008;23:2690–2. [PubMed: 18503011]
  • Pecci A, Gresele P, Klersy C, Savoia A, Noris P, Fierro T, Bozzi V, Mezzasoma AM, Melazzini F, Balduini CL. Eltrombopag for the treatment of the inherited thrombocytopenia deriving from MYH9 mutations. Blood. 2010;116:5832–7. [PubMed: 20844233]
  • Pecci A, Klersy C, Gresele P, Lee KJ, De Rocco D, Bozzi V, Russo G, Heller PG, Loffredo G, Ballmaier M, Fabris F, Beggiato E, Kahr WH, Pujol-Moix N, Platokouki H, Van Geet C, Noris P, Yerram P, Hermans C, Gerber B, Economou M, De Groot M, Zieger B, De Candia E, Fraticelli V, Kersseboom R, Piccoli GB, Zimmermann S, Fierro T, Glembotsky AC, Vianello F, Zaninetti C, Nicchia E, Güthner C, Baronci C, Seri M, Knight PJ, Balduini CL, Savoia A. MYH9-related disease: a novel prognostic model to predict the clinical evolution of the disease based on genotype-phenotype correlations. Hum Mutat. 2014a;35:236–47. [PMC free article: PMC6233870] [PubMed: 24186861]
  • Pecci A, Ma X, Savoia A, Adelstein RS. MYH9: Structure, functions and role of non-muscle myosin IIA in human disease. Gene. 2018;664:152–167. [PMC free article: PMC5970098] [PubMed: 29679756]
  • Pecci A, Verver EJ, Schlegel N, Canzi P, Boccio CM, Platokouki H, Krause E, Benazzo M, Topsakal V, Greinacher A. Cochlear implantation is safe and effective in patients with MYH9-related disease. Orphanet J Rare Dis. 2014b;9:100. [PMC free article: PMC4105151] [PubMed: 24980457]
  • Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–24. [PMC free article: PMC4544753] [PubMed: 25741868]
  • Saposnik B, Binard S, Fenneteau O, Nurden A, Nurden P, Hurtaud-Roux MF, Schlegel N. French MYH9 networka. Mutation spectrum and genotype-phenotype correlations in a large French cohort of MYH9-related disorders. Mol Genet Genomic Med. 2014;2:297–312. [PMC free article: PMC4113270] [PubMed: 25077172]
  • Savoia A, De Rocco D, Panza E, Bozzi V, Scandellari R, Loffredo G, Mumford A, Heller PG, Noris P, De Groot MR, Giani M, Freddi P, Scognamiglio F, Riondino S, Pujol-Moix N, Fabris F, Seri M, Balduini CL, Pecci A. Heavy chain myosin 9-related disease (MYH9-RD): neutrophil inclusions of myosin-9 as a pathognomonic sign of the disorder. Thromb Haemost. 2010;103:826–32. [PubMed: 20174760]
  • 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, Laffan MA, Freson K, Ouwehand WH, Kunishima S, Turro E, et al. Rare variants in GP1BB are responsible for autosomal dominant macrothrombocytopenia. Blood. 2017;129:520–4. [PMC free article: PMC6037295] [PubMed: 28064200]
  • Sekine T, Konno M, Sasaki S, Moritani S, Miura T, Wong WS, Nishio H, Nishiguchi T, Ohuchi MY, Tsuchiya S, Matsuyama T, Kanegane H, Ida K, Miura K, Harita Y, Hattori M, Horita S, Igarashi T, Saito H, Kunishima S. Patients with Epstein-Fechtner syndromes owing to MYH9 R702 mutations develop progressive proteinuric renal disease. Kidney Int. 2010;78:207–14. [PubMed: 20200500]
  • Seri M, Pecci A, Di Bari F, Cusano R, Savino M, Panza E, Nigro A, Noris P, Gangarossa S, Rocca B, Gresele P, Bizzaro N, Malatesta P, Koivisto PA, Longo I, Musso R, Pecoraro C, Iolascon A, Magrini U, Rodriguez Soriano J, Renieri A, Ghiggeri GM, Ravazzolo R, Balduini CL, Savoia A. 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. Medicine (Baltimore). 2003;82:203–15. [PubMed: 12792306]
  • Vassallo P, Westbury SK, Mumford AD. FLNA variants associated with disorders of platelet number or function. Platelets. 2020;31:1097–100. [PubMed: 32299270]
  • Verver E, Pecci A, De Rocco D, Ryhänen S, Barozzi S, Kunst H, Topsakal V, Savoia A. R705H mutation of MYH9 is associated with MYH9-related disease and not only with non-syndromic deafness DFNA17. Clin Genet. 2015;88:85–9. [PubMed: 24890873]
  • Verver EJJ, Topsakal V, Kunst HPM, Huygen PLM, Heller PG, Pujol-Moix N, Savoia A, Benazzo M, Fierro T, Grolman W, Gresele P, Pecci A. NMMHC-IIA mutation predicts severity and progression of sensorineural hearing loss in patients with MYH9-related disease. Ear Hear. 2016;37:112–20. [PubMed: 26226608]
  • Zaninetti C, Barozzi S, Bozzi V, Gresele P, Balduini CL, Pecci A. Eltrombopag in preparation for surgery in patients with severe MYH9-related thrombocytopenia. Am J Hematol. 2019;94:E199–E201. [PubMed: 31034630]
  • Zaninetti C, Gresele P, Bertomoro A, Klersy C, De Candia E, Veneri D, Barozzi S, Fierro T, Alberelli MA, Musella V, Noris P, Fabris F, Balduini CL, Pecci A. Eltrombopag for the treatment of inherited thrombocytopenias: a phase II clinical trial. Haematologica. 2020;105:820–8. [PMC free article: PMC7049343] [PubMed: 31273088]
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