Quote (pobeda)
у меня сидром Альпорта Х-сцеплнный домнантный тип наследования(наследственный нефрит.нейросесорная тугоухость)ХПН терминальная стадия.Тромбоцистический сидром тяжелой степени.без явлений геморрагического диатеза
Сочетание симптомов не отличимых от синдрома Альпорта (нефропатия, тугоухость) с тромбоцитопенией (макротромбоцитопенией) является проявлением совсем другой генетической болезни, связанной с мутацией гена MYH9 а не коллагена IV (как при Альпорте). Так называемый Epstein/Fechtner syndromes. Тромбоцитопения не встречается при синдроме Альпорта (за исключением тех случаев, когда речь идёт о сочетании у одного пациента двух заболеваний, не связанных между собой.
Hereditary Nephritis with
Thrombocytopenia and Giant Platelets:
Epstein and Fechtner Syndromes from Pediatric Nephrology 6 ED - 2010 Epstein and Fechtner syndromes are allelic, autosomal
dominant disorders that have some features in common
with Alport syndrome, such as hematuria, progressive
nephropathy and sensorineural deafness (149, 150). However,
these conditions are distinguished clinically from
Alport syndrome by the invariable presence of thrombocytopenia
and giant platelets. In addition, granulocytes
of patients with Fechtner syndrome display cytoplasmic
inclusions known as Dohle-like bodies, and these
patients may develop cataracts. In some patients ultrastructural
changes in GBM resemble those of Alport syndrome
(151, 152). However, glomerular expression of
type IV collagen a3, a4 and a5 chains is normal in these
patients (152).
Despite the similarities with Alport syndrome,
Epstein and Fechtner syndromes are genetically distinct
disorders. Following the mapping of the Epstein
and Fechtner loci to chromosome 2q11–13 (153, 154),
heterozygous mutations in MYH9, the gene that encodes
nonmuscle myosin heavy chain IIA (NMMHC-IIA), were
identified in patients with these disorders, as well as
in patients with two other conditions featuring giant
platelets, Sebastian syndrome and May-Hegglin anomaly,
and in nonsyndromic hereditary deafness (DFNA17)
(155–158). NMMHC-IIA is expressed in podocytes
(159), but the mechanism by which mutations in this
protein might adversely affect podocyte function is
unknown.
Table 1 Familial hematurias
Locus Protein
Alport syndrome
X-linked COL4A5 α5(IV)
Autosomal
recessive
COL4A3 α3(IV)
COL4A4 α4(IV)
Autosomal
dominant
COL4A3 α3(IV)
COL4A4 α4(IV)
Thin basement membrane nephropathy
Autosomal
dominant
COL4A3 α3(IV)
COL4A4 α4(IV)
Epstein/Fechtner syndromes
Autosomal
dominant
MYH9 Nonmuscle myosin heavy chain IIA
Одна из последних публикаций на эту тему ниже .
Genetic Disorders of Glomerular
Basement Membranes
Clifford E. Kashtan a Yoav Segal b
Departments of a Pediatrics and b Medicine, University of Minnesota Medical School, Minneapolis, Minn., USA
Nephron Clin Pract 2011;118:c9–c18
DOI: 10.1159/000320876
MYH9-Related Disease (Epstein and Fechtner
Syndromes)
Clinical Features
Epstein and Fechtner syndromes are rare autosomal
dominant kidney diseases that, together with May-Hegglin
anomaly, Sebastian syndrome and subsets of nonsyndromic
hereditary deafness constitute MYH9 -related
disease – an allelic spectrum marked by phenotypic
variability – that results from mutations in the MYH9
gene encoding NMMHC-IIA [27] . In particular, Epstein
and Fechtner syndrome were first described as variants
of Alport syndrome, with like associations of hereditary
nephritis, hearing loss and eye abnormalities, and additional
findings of thrombocytopenia and giant platelets
(macrothrombocytopenia) and leukocyte inclusions
[28–31] . The true incidence of kidney disease in MYH9 -
related disease is unknown, as case series are subject to
ascertainment bias and longitudinal studies are lacking;
however, it is possible that a significant fraction and perhaps
the majority of affected individuals have no significant
kidney disease. In selected case series, 10–63%
of affected individuals had kidney disease, variably defined
[32–35] . The severity of kidney disease in MYH9-
related disorders ranges from isolated microscopic hematuria,
to asymptomatic proteinuria with well-preserved
glomerular filtration rate, to chronic kidney
disease leading to end-stage kidney disease as early as
adolescence [36, 37] .
Hematological abnormalities are nearly universal.
Macrothrombocytopenia is common to all MYH9-related
diseases and is associated with leukocyte inclusions in
those with May-Hegglin anomaly, Sebastian syndrome
and Fechtner syndrome. Bleeding tendencies are commonly
reported. Progressive sensorineural hearing loss is
probably more common than kidney disease [35] and can
present as nonsyndromic deafness [38] . Cataract is the
most widely reported eye abnormality but occurs with
variable frequency.
Pathology
Reports of kidney biopsy findings in MYH9 -related
disease are sparse and vary by stage of disease. In early
kidney disease, light microscopic findings may be limited
to mesangial expansion [28, 39, 40] . In late-stage
disease, changes are non-specific. Electron microscopic
findings are also variable, with reports of normal GBM
ultrastructure, focal GBM thinning and thickening
with splitting [32, 36, 37, 39–42] , generally with foot
process effacement. GBM changes have been deemed
suggestive of Alport syndrome [31] . The mechanisms by
which MYH9 mutations result in kidney disease with
abnormalities of GBM ultrastructure are unknown.
NMMHC-IIA is expressed in podocytes but at reduced
levels in MYH9 -related disease [32, 43] , suggesting that
diminished or defective NMMHC-IIA could adversely
affect podocyte function including GBM synthesis and
remodeling. NMMHC-IIA is also expressed within arterioles
and proximal tubular cells, suggesting that injury
at these sites or platelet and/or leukocyte abnormalities
contribute to kidney disease. Studies of nonmuscle
myosin heavy chain expression suggest that
family members II-B and II-C may compensate for II-A
in kidney and eye but not in blood cells [44] . Overall patterns
of type IV collagen expression appear to be preserved
[42] .[size=10][size=12][b][color=blue][size=22][color=red]
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