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historically , 50% of spontaneously expelled abortuses have been thought to be chromosomally abnormal ; about 60% are trisomies .
in general , trisomy 16 is the most frequent chromosomal abnormality , followed by trisomy 21 and trisomy 22 .
so far only 1 case of a female fetus with multiple congenital malformations associated with full trisomy 5 has been described .
we present a case of de novo full trisomy 5 in a spontaneous abortion sample .
a young couple with normal constitutional karyotype experienced the second spontaneous abortion at 9 weeks of gestation , with the cytogenetic formula 47,xx,+5 in all analyzed cells .
the routine cytogenetic analysis of miscarriages is still an uncommon practice , but it can have a great impact on the management of couples with repeated pregnancy wastage . besides of the obvious cost benefit for health care , such analysis would help the physician to decide about future patient management , as well as planning the genetic counseling .
spontaneous abortion is a common clinical problem that occurs in 1015% of all clinically recognized pregnancies . historically , 50% of spontaneously expelled abortuses have been thought to be chromosomally abnormal .
about 60% are trisomies , 20% are monosomies , and 15% have ploidy , especially triploidy .
most of these terminate in utero , making the extra or missing chromosome status the leading known cause of miscarriage . in the case of a numerical chromosomal anomaly in spontaneous abortion ,
its incidence rises from 15% in woman under 25 years of age to 35% after age 38 .
there is limited epidemiological evidence for a paternal age effect , which is more likely to involve meiotic ii errors of the sex chromosomes .
however , it has recently been shown that there is a correlation between age and increase in sperm aneuploidy .
although rare , paternally derived trisomy tends to abort earlier . these and other differences suggest that constitutional aneuploidy arises by multiple mechanisms .
in general , trisomy 16 is the most frequent chromosomal abnormality , and accounts for approximately a third of chromosomal abnormalities in early pregnancy .
several cases ( in a clinically recognized pregnancy ) of trisomy 5 in aborted material have been reported . however , despite of the molecular cytogenetic techniques used for aneuploidy detection , trisomy 5 in aborted material has been observed only in sporadic cases [ 58 ] . even by using comparative genomic hybridization ( cgh ) technique ,
trisomy 5 was found in only 1 first trimester missed abortion . in all other cgh / spontaneous abortion studies
we present here a case of a rare type of mutation  single trisomy 5 in spontaneous abortion sample .
cells ( fibroblasts ) isolated from product of conception were cultured , and cytogenetic analysis by g - banding showed 47,xx,+5   karyotype ( figure 1 ) . a young childless couple ( a 27-year - old woman and a 30-year - old man ) with normal constitutional karyotype ( 46,xx and 46,xy ) visited clinical hospital split , croatia after the woman experienced her second spontaneous abortion .
it was not cytogenetically analyzed ; clinically it was diagnosed as a missed abortion at 8 weeks of gestation .
pathohistological analysis revealed extensive arias stella reaction in endometrial glands and partially degenerative and mildly hydropic chorionic villi , most of them avascular or with faintly visible remnants of former fetal vessels .
the second spontaneous abortion was at 9 weeks of gestation , with the cytogenetic formula 47,xx,+5 .
pathohistology revealed the same arias stella reaction , with mesenchymal and immature intermediate well vascularized villi . in the family history ,
the wife s sister had 2 spontaneous abortions at the same gestational period , while the husband s mother had 1 spontaneous abortion .
the research conformed to the helsinki declaration and to the ethics committee , clinical center split .
all patients samples and clinical details were obtained upon receiving patients consent and the ethics committee approval . during normal pregnancy , to prevent bleeding , the concentrations of inhibitors of fibrinolysis and the concentration of many clotting factors rise to achieve a precise balance between hypofibrinolysis and hypercoagulation .
therefore , the coordinated expression of all of these factors plays a fundamental role in maintaining normal pregnancy .
however , coagulation homeostasis defects ( thrombotic , hypercoaguable ) are quite common during pregnancy , leading to fetal wastage due to thrombosis of early placental vessels [ 1416 ] . as certain polymorphisms in some maternal thrombophylia genes
are associated with pronounced thrombotic defects [ 1720 ] we additionally tested mother s blood sample for the presence of specific polymorphisms in genes ace , pai - i , mthfr , fvl and fii .
the ace gene product , angiotensin - i converting enzyme , has a physiological function in the fibrinolysis pathway .
the enzyme converts angiotensin i to angiotensin ii , which is very important in regulation of fetoplacental complex functions .
this regulation is mainly attributed to the insertion / deletion ( i / d ) of a 287 bp alu - repeat polymorphism in intron 16 of the ace gene , the so - called ace i / d polymorphism .
the presence of the d / d alleles correlates with increase of ace concentration in blood and subsequently with the increase of pai-1 expression , resulting in reduced fibrinolysis .
pai - i ( plasminogen activator inhibitor-1 ) is a key regulating element in the fibrinolysys cascade , whose expression is influenced by angiotensin ii plasma level , as well as 4g/5 g polymorphism in the pai-1 promoter , at the position -675 .
comparable to ace d / d alleles , 4g/4 g alleles potentiate expression of the pai-1 gene , leading to reduction of fibrinolysis .
the relationship between the mthfr ( methylenetetrahydrofolate reductase ) gene mutation and spontaneous abortion is still not clear .
the gene codes for the enzyme that catalyses the reduction of 5,10-methylenetetrahydrofolate to a predominant circulating form of folate , which allows remethylation of homocystein in methionine .
however , it has been reported that nucleotide change ( polymorphism ) at the position 667 ( c667 t ) results in an alanine to valine substitution ( codon 225 , predicted catalytic domain of mthfr ) and lowers enzyme activity , leading to the hyperhomocysteinemia and elevated risk of spontaneous abortion .
coagulation factor v leiden ( fvl ) and factor ii ( fii , prothrombin ) gene mutations are the most common causes of thrombophilia and placental dysfunction .
fvl gene mutation ( arg506gln substitution at nucleotide position 1691 ) causes resistance to activated protein c ( apc ) .
mutation in fii gene ( g20210a substitution in the 3 untranslated region ) leads to elevated blood prothrombin level , which in turn causes increased risk for thrombosis and spontaneous abortion . only ace gene analyzed in mothers blood lymphocytes exhibited polymorphism ( homozigosity for d allele , dd 190 bp ) associated with an elevated risk for spontaneous abortion due to the elevated pai-1 concentration and reduced fibrinolysis .
as mentioned earlier , only a few cases of trisomic fetuses have been described . by using conventional and trypsin g - staining and by dna typing using highly polymorphic microsatellite markers , trisomy 5 in spontaneous abortion material
comparative genomic hybridization , a powerful new molecular cytogenetic technique , has been used for chromosome analysis in spontaneous abortions in only a limited number of studies [ 1012 ] ; however , trisomy 5 was recorded in only 1 first trimester missed abortion .
even combined qf - pcr and malpa molecular analysis of total 1539 miscarriage products did not reveal any trisomy 5 cases . however , when double aneuploidy , which is a relatively rare phenomenon , is concerned , 7 more cases of chromosome 5 trisomy were described .
the double trisomies 5/8 were observed in 3 cases   and double trisomies 5/2 , 5/7 , 5/12 and 5/16 in single cases [ 2831 ] .
in addition to the maternal - age effect mentioned earlier , trisomy occurrence depends also on chromosome structure , including very small effects for the large chromosomes ( groups a and b ) , increased effect on chromosome 16 , and exponentially increased effect on chromosome 21 .
little is known about the possible phenotype of trisomic spontaneous abortions . in a study correlating parental origin of trisomy with phenotype , zaragozza et al
.   found no difference in the proportion of cases with trophoblastic hyperplasia , fetal tissue , nucleated red blood cells , or hydropic villi among paternally or maternally derived trisomies 2 , 7 , 15 , or 22 . in the case of the young couple described in this paper ,
this glandular change is a physiologic response to the presence of chorionic tissue and is probably not directly related to trisomy 5 .
for still unknown reasons , abortion due to the aneuploidy occurs frequently in people with normal constitutional karyotype . however , the routine cytogenetic analysis of miscarriages is still an uncommon practice that has a great impact on the management of couples with repeated pregnancy wastage .
in addition to the obvious cost benefit for health care , such analysis would help the physician to decide about future patient management as well as planning genetic counseling , considering that miscarriage can have a deep emotional and psychological effect on both partners .
summarybackgroundhistorically , 50% of spontaneously expelled abortuses have been thought to be chromosomally abnormal ; about 60% are trisomies . 
 in general , trisomy 16 is the most frequent chromosomal abnormality , followed by trisomy 21 and trisomy 22 . 
 so far only 1 case of a female fetus with multiple congenital malformations associated with full trisomy 5 has been described.case reportwe present a case of de novo full trisomy 5 in a spontaneous abortion sample . 
 a young couple with normal constitutional karyotype experienced the second spontaneous abortion at 9 weeks of gestation , with the cytogenetic formula 47,xx,+5 in all analyzed cells.conclusionsthe routine cytogenetic analysis of miscarriages is still an uncommon practice , but it can have a great impact on the management of couples with repeated pregnancy wastage . besides of the obvious cost benefit for health care , such analysis would help the physician to decide about future patient management , as well as planning the genetic counseling .