31 research outputs found
The Risk of Chromosomal Abnormalities in Cases of Minor and Major Fetal Anomalies in the Second Trimester
Currently, noninvasive intrauterine screening for most chromosome abnormalities is available, but ultrasound examinations also play an important role during pregnancy, by drawing the attention to the suspect of a possible abnormality. Fetal ultrasound disorders can be classified into two major groups: (1) Major abnormalities are actually diagnosed malformations that are often associated with certain chromosome abnormalities but may be associated with other disorders (multiplex malformation) and may occur as isolated disorders (e.g., cardiac disorders, duodenal atresia, omphalocele, cystic hygroma (CH)). (2) Minor anomalies (“soft markers”) are not abnormal in themselves but are mild abnormalities that may occur in normal pregnancy but also increase the risk of certain chromosome aberrations. The minor anomalies in the second trimester include thickened nuchal fold (NF), mild ventriculomegaly, pyelectasis, hyperechogenic bowels, hyperechogenic papillary muscle, and shorter long bones. Plexus choroid cyst which is classified as a minor marker does not increase the risk of Down syndrome but increases the risk of trisomy 18 (Edwards syndrome). We want to emphasize the importance of screening of minor and major ultrasound abnormalities in detecting chromosomal abnormalities in the second trimester
Congenital Fetal Anomalies and the Role of Prenatal Ultrasound
The ultrasound is the most widely used diagnostic tool in obstetrics nowadays, in particular in the detection of developmental disorders. However, it is important to know which are those disorders that can be detected prenatally with great certainty, and which ones can be detected only partially or not at all prior to giving birth. Pregnant women have high expectations, that any abnormalities should be fully recognizable and detected early during pregnancy, and this often leads to damages lawsuits. Thus, the right information is essential, so the doctors providing information also must have up to date knowledge about the effectiveness of ultrasound diagnostics. Prenatal diagnostics also entails enormous medical professional responsibility, since the consequences of an accidental inaccurate diagnosis can have significant consequences for both the fetus and the family. Thus, it is important to determine that how early and in what proportion the ultrasound protocol of the current Hungarian pregnancy care system is able to detect the individual disorder groups
Magzati-újszülöttkori fejlődési rendellenességek praenatalis ultrahangvizsgálatának eredményessége, a nehézségi és a bizonytalansági faktorok vizsgálata
Absztrakt:
Bevezetés és célkitűzés: A magzati fejlődési rendellenességek
születéskori prevalenciája 2–3% körül van. Célunk a praenatalis
ultrahangvizsgálat hatékonyságának az elemzése volt a fejlődési rendellenességek
felismerésében. Módszer: Vizsgálatunk során hét év anyagában
1200, fejlődési rendellenességben szenvedő magzat praenatalis ultrahang- és
postnatalis klinikai, illetve fetopatológiai adatait dolgoztuk fel.
Eredmények: Ezerkétszáz, fejlődési rendellenességben
érintett magzat adatait dolgoztuk fel. Az anyai átlagéletkor a szülés/vetélés
idején 29,96 ± 5,88 év volt. Az 1200-ból 671 esetben végződött szüléssel a
várandósság, a gesztációs kor átlaga a szülés idején 35,26 ± 4,2 hét volt, míg a
magzatok súlya 2408,67 ± 944,41 g. Ötszázhuszonkilenc vetélés fordult elő, a
gesztációs kor átlaga 19,88 ± 2,53 hét volt. Az 1200 magzatból 73-nál fordult
elő kromoszóma-rendellenesség, 211 esetben pedig multiplex malformatio.
Megállapíthattuk, hogy a magzati craniospinalis rendellenességek és mellkasi
eltérések nagy hatékonysággal vizsgálhatók a méhen belüli magzatnál (72,65% és
67,7%). Magas szenzitivitással tudtuk kimutatni a hasi malformatiókat (59,58%),
az urogenitalis rendellenességeket (54,55%), illetve a végtag- és csontrendszeri
eltéréseket (50%). Ezzel szemben az arc és nyak rendellenességeinek kimutatása
alacsony hatékonyságú volt (31,85%). Következtetések: Az esetek
körülbelül felében egyezett meg a postnatalisan/vetélést követően talált
rendellenesség a praenatalisan diagnosztizált magzati anomáliával. Az
eredményeink azt igazolják, hogy az ultrahangvizsgálat a congenitalis
malformatiók diagnosztikájában fontos szerepet játszik, azonban valamennyi
fejlődési rendellenesség kimutatását nem teszi lehetővé. Orv Hetil. 2017;
158(45): 1794–1801.
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Abstract:
Introduction and aim: The birth prevalence of congenital
malformations is around 2-3%. The aim of this study was to examine the efficacy
of ultrasound diagnostics in detecting congenital malformations.
Method: We have processed the prenatal sonographic and
postnatal clinical details of 1867 inborn abnormalities in 1200 fetuses over a
7-year period. Results: The mean maternal age upon
delivery/abortion was 29.96 ± 5.88 years. In 671 cases, the pregnancy concluded
in delivery with a mean gestational age of 35.26 ± 4.2 weeks and mean weight of
2408.67 ± 944.41g. In case of the 529 abortions the mean gestational age was
19.88 ± 2.53 weeks. Seventy-three fetuses were chromosomally abnormal, while 211
had multiple malformations. Prenatal ultrasound was highly sensitive in the
detection of central nervous system and thoracic anomalies in utero (72.65% vs.
67.7% sensitivity). The detection rate was high in case of abdominal (59.58%),
urogenital (54.55%), and limb/skeletal (50%) malformations as well. However, the
diagnosis of face/neck anomalies was somewhat less efficient (31.85%).
Conclusions: In approximately half of the cases,
postnatally diagnosed abnormalities coincided with the prenatally discovered
congenital malformations. The results have confirmed that ultrasonography plays
an important role in diagnosing malformations prenatally but it fails to detect
all of the developmental abnormalities. Orv Hetil. 2017; 158(45): 1794–1801
Molecular cytogenetic analysis of Xq critical regions in premature ovarian failure.
BACKGROUND: One of the frequent reasons for unsuccessful conception is premature ovarian failure/primary ovarian insufficiency (POF/POI) that is defined as the loss of functional follicles below the age of 40 years. Among the genetic causes the most common one involves the X chromosome, as in Turner syndrome, partial X deletion and X-autosome translocations. Here we report a case of a 27-year-old female patient referred to genetic counselling because of premature ovarian failure. The aim of this case study to perform molecular genetic and cytogenetic analyses in order to identify the exact genetic background of the pathogenic phenotype. RESULTS: For premature ovarian failure disease diagnostics we performed the Fragile mental retardation 1 gene analysis using Southern blot technique and Repeat Primed PCR in order to identify the relationship between the Fragile mental retardation 1 gene premutation status and the premature ovarion failure disease. At this early onset, the premature ovarian failure affected patient we detected one normal allele of Fragile mental retardation 1 gene and we couldn't verify the methylated allele, therefore we performed the cytogenetic analyses using G-banding and fluorescent in situ hybridization methods and a high resolution molecular cytogenetic method, the array comparative genomic hybridization technique. For this patient applying the G-banding, we identified a large deletion on the X chromosome at the critical region (ChrX q21.31-q28) which is associated with the premature ovarian failure phenotype. In order to detect the exact breakpoints, we used a special cytogenetic array ISCA plus CGH array and we verified a 67.355 Mb size loss at the critical region which include total 795 genes. CONCLUSIONS: We conclude for this case study that the karyotyping is definitely helpful in the evaluation of premature ovarian failure patients, to identify the non submicroscopic chromosomal rearrangement, and using the array CGH technique we can contribute to the most efficient detection and mapping of exact deletion breakpoints of the deleted Xq region
Praenatalisan diagnosztizált Pallister–Killian-szindróma esete = Prenatally diagnosed case of Pallister–Killian syndrome
Absztrakt:
A Pallister–Killian-szindróma egy ritka, sporadikusan előforduló genetikai
rendellenesség, amelynek hátterében a 12-es kromoszóma rövid karjának
mozaiktetraszómiája áll. A kórkép jellemzői a szellemi fogyatékosság,
craniofacialis dysmorphia, idegrendszeri tünetek, epilepszia és egyéb szervi
rendellenességek. Praenatalis diagnózisa nehéz, az ultrahangvizsgálaton észlelt
magzati eltérések alapján elvégzett invazív citogenetikai és molekuláris
genetikai vizsgálatok igazolhatják a kórképet. Közleményünkben egy 36 éves
primipara esetét mutatjuk be. A 19. terhességi héten, a II. trimeszteri
rutin-ultrahangszűrés során a magzaton többszörös minor jelek ábrázolódtak
(mérsékelt polyhydramnion, rövid csöves csontok, craniofacialis eltérések,
borderline agyi oldalkamrák). Az elvégzett magzatvíz-mintavétel a sejtek közel
50%-ában szám feletti marker kromoszómát igazolt. A klasszikus G-sáv-technika
alapján felmerült, hogy a marker a 12-es kromoszóma rövid karjának
izokromoszómája. Az alkalmazott FISH-próbák (21-es, 18-as, 13-as, X-,
Y-kromoszóma) az észlelt marker eredetét nem tudták meghatározni, ezért
multicolour FISH-technikával vizsgáltuk a mintákat. Az elvégzett módszer
segítségével igazoltuk a szám feletti kromoszómadarab 12-es kromoszóma rövid
karjának mozaiktetraszómiáját (46,XY[13]/47,XY,+i(12)(p10)[12].ish
i(12)(p10)(wcp12+). A praenatalisan felállított diagnózis tehát a magzat
Pallister–Killian-szindrómája. A vetélésindukciót követően elvégzett vizsgálatok
(fetopatológiai feldolgozás, köldökzsinórvér, magzati fibroblast) megerősítették
a diagnózist. A nemzetközi adatok szerint a fenti ritka betegséggel eddig
körülbelül 200 megszületett ember él, a praenatalisan igazolt és közölt esetek
száma mintegy 100. Tudomásunk szerint a fenti magzat az első, praenatalisan
diagnosztizált eset Magyarországon. Orv Hetil. 2018; 159(21): 847–852.
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Abstract:
Pallister–Killian syndrome (PKS) is a rare, sporadic genetic disorder that is
caused by the mosaic presence of a supernumerary marker chromosome,
isochromosome 12p. The syndrome is a polydysmorphic condition characterized by
mental retardation, craniofacial dysmorphism, hypotonia, seizures, epilepsy and
certain organic malformations (diaphragmatic hernia, congenital heart disease).
Prenatal diagnosis is challenging due to the mosaic tissue-specific distribution
of the chromosomal disorder and highly variable phenotype. Prenatal diagnosis is
often accidental, however, appropriate laboratory techniques based on the second
trimester ultrasound anomalies provide accurate prenatal diagnosis. We report a
case of a 36-year-old primipara with second trimester ultrasound markers
(polyhydramnion, ventriculomegaly, rhizomelic micromelia, abnormal facial
profile). The patient underwent amniocentesis, the conventional karyotyping
revealed a supernumerary chromosome in nearly 50 percent of amniocytes. FISH and
targeted multicolour FISH probes verified mosaic tetrasomy of the short arm of
chromosome 12 of the fetus. Fetopathological examinations and analysis of fetal
tissues and blood confirmed the prenatal diagnosis. To our knowledge, this is
the first reported case of prenatally diagnosed Pallister–Killian syndrome in
Hungary. Orv Hetil. 2018; 159(21): 847–852
Expression of VEGF in neonatal urinary obstruction: does expression of VEGF predict hydronephrosis?
BACKGROUND In animal studies, the inhibition of VEGF activity results in high mortality and impaired renal and glomerular development. Mechanical stimuli, like mechanical stretch in respiratory and circulatory systems, results in an elevated expression of VEGF. In animal models, the experimental urinary obstruction is associated with stretching of tubular cells and activations of the renin-angiotensin system. This results in the upregulation of vascular endothelial growth factor (VEGF) and TNF-alfa. MATERIAL AND METHODS Tissue samples from urinary tract obstruction were collected and immunohistochemistry was performed in 14 patients (average age: 7.1+/-4.1 years). The control histology group consisted of ureteropelvic junction tissue from 10 fetuses after midtrimester artificial abortion. The fetuses did not have any failure at ultrasound screening and pathological examination. The mean gestational age was 20.6 weeks of gestation (+/-2.2SD). Expression of VEGF was detected with immunohistochemistry method. RESULTS Expression of VEGF was found in varying intensity in the submucosa and subserosa layers, but only in the test tissue (placental tissue). The tissue of the patients with urinary obstruction and the tissue of the fetal ureteropelvic junction without urinary obstruction were negative for expression of VEGF. The repeated examination showed negative cells and no color staining. CONCLUSIONS The pressure due to congenital urogenital obstruction resulting in mechanical stress in cells did not increase the expression of VEGF in young children in our study. To find a correlation between urogenital tract obstruction and increased expression of VEGF, we need to perform more examinations because the connection may be of therapeutic significance
A microarray-komparatív genomhibridizálás (arrayCGH) praenatalis alkalmazása. Javaslat a hazai bevezetésre = Chromosomal microarray comparative genome hybridization (arrayCGH) in prenatal settings. Proposal for Hungarian application in clinical practice
Absztrakt:
Az invazív mintavétel kapcsán elvégzett hagyományos magzati kromoszómavizsgálat a
mai napig a praenatalis diagnosztika alapvető vizsgálómódszere. Felhasználásának
a fénymikroszkópos vizsgálat felbontási képessége szab határt. A
kariotipizálással nem felismerhető, szubmikroszkópos
kromoszóma-rendellenességek, microdeletiók és microduplicatiók,
kópiaszám-variációk (CNV-k) vizsgálatára a nagy felbontású molekuláris
vizsgálóeljárások biztosítanak lehetőséget. A kromoszomális összehasonlító
microarray-vizsgálat (array-komparatív genomhibridizálás – arrayCGH) alkalmas az
anyai életkortól függetlenül előforduló kópiaszám-variációk prae- és postnatalis
kimutatására. A módszer a fejlett országok orvosi gyakorlatában rutinszerűen
alkalmazott eljárás a magzati diagnosztikában. Az elmúlt egy évtized külföldi
eredményei alapján alkalmazása ultrahangeltérést nem mutató magzatok esetén
körülbelül 1–2%, strukturális ultrahangeltérést mutató magzatoknál körülbelül
5–7% többlet genetikai információval szolgál a hagyományos
kromoszómavizsgálattal szemben. Közleményünkben áttekintjük az arrayCGH
módszerét, praenatalis alkalmazásának nemzetközi gyakorlatát, s javaslatokat és
indikációs kört fogalmazunk meg a módszer praenatalis használatának
magyarországi bevezetésére. Orv Hetil. 2019; 160(13): 484–493.
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Abstract:
Invasive prenatal testing and conventional G-banding chromosome analysis have
been considered to be the gold standard of fetal cytogenetic diagnosis. Standard
karyotyping is, however, constrained by the limits of the resolution of using a
microscope. The advantage of molecular karyotyping, array based methods is the
evaluation of sub-microscopic copy number changes across the whole genome in a
single analysis. The application of array comparative genome hybridization has
greatly increased the detection of pathogenic chromosomal abnormalities in
prenatal settings. Based on available data in the international literature of
the last decade, the clinical utility of arrayCGH is the recognition of some
1–2% and 5–7% additional genetical information compared to metaphase karyotype
alone in fetuses without ultrasound anomaly and in fetuses with
ultrasonographically detected malformations, respectively. Thus arrayCGH
improves the prenatal diagnosis of genetic abnormalities mainly in fetuses with
structural sonographic findings. In the present paper we review the literature
of chromosomal microarray and make a proposal for the application of the method
in Hungarian prenatal genetical practice. Orv Hetil. 2019; 160(13): 484–493
A ritka kromoszóma-rendellenességek és a fetoplacentaris mozaikosság jelentősége a praenatalis diagnosztikában a nem invazív szűrővizsgálatok tükrében
Introduction and objective: To determine the prevalence of microscopically visible de novo atypical chromosomal aberrations and fetoplacental mosaicism in a prenatal tertial referral center, and to investigate the maternal and fetal characteristics in connection with genomewide non-invasive prenatal screening. Method: Retrospective cohort study from 2014 to 2019 of pregnancies with invasive genetic analysis. Results: In the cohort of 2504 cases, the proportion of CVS was 53.3%. We diagnosed 200 chromosomal aberrations (8%), including 13.5% of de novo rare chromosomal aberrations (14 rare autosomal trisomies, 6 polyploidies, 5 structural aberrations and 2 small supernumerary marker chromosomes). The rate of fetoplacental mosaicism was 12.4%/77.8% in common/atypical chromosomal aberrations (p = 0.001) and confined to placenta in 17/40 cases. Associated ultrasound abnormalities were abnormal nuchal translucency and major malformations in 58% and 35% with common trisomies and 11% (p = 0.006) and 67% (p = 0.047) with true mosaic cases of rare abnormalities, respectively. Major ultrasound malformation was facial dysmorphism with rare aberrations. Potential application of genomewide non-invasive prenatal test in atypical chromosomal aberrations presumably would have been false-positive in 12 cases (44%), false-negative in 1 case (3.7%), and would have early detected 2 cases of rare autosomal trisomies (7.4%) without ultrasound anomalies. Conclusion: Structural ultrasound malformations with normal nuchal translucency thickness may be indicative of rare chromosomal aberrations. Application of genomewide non-invasive prenatal test is an alternative of early diagnostic methods with a potential of discordant results due to mosaicism. Knowledge about the presence of fetoplacental mosaicism influences risk estimation and genetic counseling, detailed cytogenetic characterization is of utmost importance. © Szerző(k)
Complex X chromosome rearrangement associated with multiorgan autoimmunity
BACKGROUND: Turner syndrome, a congenital condition that affects 1/2,500 births, results from absence or structural alteration of the second sex chromosome. Turner syndrome is usually associated with short stature, gonadal dysgenesis and variable dysmorphic features. The classical 45,X karyotype accounts approximately for half of all patients, the remainder exhibit mosaicism or structural abnormalities of the X chromosome. However, complex intra-X chromosomal rearrangements involving more than three breakpoints are extremely rare. RESULTS: We present a unique case of a novel complex X chromosome rearrangement in a young female patient presenting successively a wide range of autoimmune diseases including insulin dependent diabetes mellitus, Hashimoto's thyroiditis, celiac disease, anaemia perniciosa, possible inner ear disease and severe hair loss. For the genetic evaluation, conventional cytogenetic analysis and FISH with different X specific probes were initially performed. The complexity of these results and the variety of autoimmune problems of the patient prompted us to identify the exact composition and breakpoints of the rearranged X as well as methylation status of the X chromosomes. The high resolution array-CGH (assembly GRCh37/hg19) detected single copy for the whole chromosome X short arm. Two different sized segments of Xq arm were present in three copies: one large size of 80,3 Mb from Xq11.1 to Xq27.3 region and another smaller (11,1 Mb) from Xq27.3 to Xq28 region. An 1,6 Mb Xq27.3 region of the long arm was present in two copies. Southern blot analysis identified a skewed X inactivation with approximately 70:30 % ratios of methylated/unmethylated fragments. The G-band and FISH patterns of the rearranged X suggested the aspect of a restructured i(Xq) chromosome which was shattered and fortuitously repaired. The X-STR genotype analysis of the family detected that the patient inherited intact maternal X chromosome and a rearranged paternal X chromosome. The multiple Xq breakages and fusions as well as inverted duplication would have been expected to cause a severe Turner phenotype. However, the patient lacks many of the classic somatic features of Turner syndrome, instead she presented multiorgan autoimmune diseases. CONCLUSIONS: The clinical data of the presented patient suggest that fragmentation of the i(Xq) chromosome elevates the risk of autoimmune diseases