Epstein Syndrome

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Classification according to ICD-10
N04.9 Nephrotic Syndrome
ICD-10 online (WHO version 2019)

The Epstein syndrome is a very rare autosomal - dominant inherited disease . It is caused by a mutation in the MYH9 gene. Epstein syndrome, together with Sebastian syndrome , Fechtner syndrome and May-Hegglin anomaly, belongs to the group of MYH9-associated diseases.

Cause and genetics

The autosomal dominant inheritance
From left to right: erythrocyte (red blood cell), platelet (activated) and leukocyte

The cause of Epstein syndrome is a point mutation of the MYH9 gene , which is located in humans on chromosome 22 gene locus q11.2.

The gene codes for the heavy chain of a non-muscle myosin type IIA (NMMHC-IIA). This protein is in some blood cells, including monocytes and platelets , in the cochlea ( cochlear ) and in the kidneys expressed . The mutation R702H obviously causes a conformational change in the head of the NMMHC-IIA protein. The consequence of this is a disturbance in the aggregation of the protein into Döhle bodies , which causes a faulty organization of the cytoskeleton in the megakaryocytes , the precursor cells of the platelets. This is the cause of macrothrombocytopenia , which is manifested by a lack of platelets (a so-called thrombocytopenia ) and oversized platelets with leukocyte inclusions. The size of the platelets can even exceed that of erythrocytes.

Epidemiology and prevalence

Due to the rarity of Epstein syndrome, no reliable data on its epidemiology and prevalence are available. The prevalence, however, is well below 1: 100,000. Fewer than 100 families have been described with this syndrome to date.

Symptoms and diagnosis

Corresponding to the sites of NMMHC-IIA gene expression, the symptoms of Epstein's syndrome were also manifested. Patients with Epstein syndrome show a lack of platelets (thrombocytopenia) and an additional functional disorder of the platelets ( thrombocytopathy ). The platelets present are considerably larger than in unaffected people ( macrothrombocytopenia ).

Some of the patients develop progressive hearing loss , especially in the high frequency range. In addition, glomerulonephritis and inflammation of the kidney filters can set in. Both diseases do not inevitably arise, however, since the aggregation disturbance of NMMHC-IIA can be compensated for by another myosin form (type IIB).

The symptoms of kidney dysfunction and hearing problems cannot be distinguished from those of Fechtner's or Alport's syndrome . In contrast to the other MYH9-associated diseases, no inclusions in the leukocytes are visible in Epstein syndrome.

Glomerulonephritis and hearing loss occur later and not regularly, as the aggregation disorder can be compensated in situ by another form of myosin (type IIB).

therapy

The therapy is essentially symptomatic. A platelet transfusion may be necessary prior to surgery .

discovery

Epstein syndrome was first described in 1972 by Charles J. Epstein et al.

Individual evidence

  1. ↑ Human hg38 chr22: 35,007,273-35,113,958 UCSC Genome Browser v391. Retrieved January 6, 2020 .
  2. ↑ Human Gene MYH9 (uc003apg.1) Description and Page Index. Retrieved January 6, 2020 .
  3. ↑ JA Martignetti et al .: The gene for May-Hegglin anomaly localizes to a <1-Mb region on chromosome 22q12.3-13.1. In: Am J Hum Genet. 66/2000, pp. 1449-1454. PMID 10739770
  4. ↑ M. Seri et al.: Epstein syndrome: another renal disorder with mutations in the nonmuscle myosin heavy chain 9 genes. In: Hum Genet. 110/2002, pp. 182-186. PMID 11935325
  5. ↑ a b c C. Trichet: Epstein syndrome. October 2006.
  6. ↑ a b R. E. Scharf: Congenital and acquired thrombocytopenias. In: Hemostaseology. 23/2003, pp. 159-169.
  7. ↑ CJ Epstein et al.: Hereditary macrothrombocytopathia, nephritis and deafness. In: Am. J. Med. 52/1972, pp. 299-310. PMID 5011389 .

literature

Web links