Frequency of chromosomal aberrations in material from abortions

Summary Examination of fetal tissue from spontaneous miscarriages shows that 50-70% of them were caused by abnormalkaryotype. The most frequent genetic abnormalities include abnormal number of chromosomes, aberration of chromosomes structure and chromosome mosaic anomalies. Objective: the aim of the study was to find out whether there is any difference in the frequency of chromosomal aberrations in patients who miscarried for the first time comparing to patients with recurrent miscarriages. Material and methods: Examination was performed on 129 miscarriage material samples from 128 women. Fluorescent hybridization in-situ (FISH) was used for genetic examination. Results: We received 120 results in which 45 (37,5%) were abnormal. The most frequent chromosomal aberration was trisomy, followed by triploidy and monosomy of chromosome X. Among 59 samples from first miscarriage we found 25 abnormal karyotypes. In the 61 samples from the second, third and the next miscarriages we found 20 chromosomal abnormalities. Conclusions: Frequency of chromosomal aberrations in the tissue from the first miscarriage is significantly higher than in samples from second or following miscarriages, which means that genetic factors are less likely to induce recurrent miscarriages. Genetic results confirm that most chromosomal abnormalities arise de-novo

Do chromosomal abnormalities reappear in subsequent pregnancies and how often?

Abstract Objective: Genetic factors are the most common causes of spontaneous abortions. 50% to 80% of first-trimester abortions reveal chromosome abnormalities. Evidence for the recurrence of the same or another chromosome abnormality in the next pregnancy is scarce. The aim: The aim of our study was to estimate recurrence risk of abortus aneuploidy and to find out whether karyotyping of the abortus allows the prognose subsequent pregnancy outcomes. Material and methods: Paraffin-embedded chorions have undergone cytogenetic examination using FISH with chromosome-specific probes. 57 chorions from 26 women have been assessed, including chorions from two consecutive abortions from 18 women and chorions from three consecutive abortions from 5 women. Results: 38.6% of 57 specimens had chromosome aberrations. The most prevalent anomalies were 16, 21 and 18 trisomies. 23 patients had a subsequent abortion karyotyped; 15 had a normal initial karyotype and 8 had an aberrant initial karyotype. 3 out of the 8 patients had a repeated chromosome anomaly. 5 out of the 15 patients who initially miscarried an aneuploid embryo, had a subsequent miscarriage of an aneuploid embryo. Only 3 (13.04%) out of the 23 patients displayed aneuploidy in each abortus. Conclusion: 1. Chromosome aberrations can reappear in subsequent pregnancies in the same patient and may be the cause of recurrent miscarriages. 2. The value of embryo/fetal karyotyping is not decisive in prognosis of subsequent pregnancy outcome. 3. Abnormal fetal karyotype can occur regardless of other causes of pregnancy loss

Clinical expression of Holt-Oram syndrome on the basis of own clinical experience considering prenatal diagnosis

Objectives: Holt-Oram syndrome manifests with defects of upper limbs, pectoral girdle and cardiovascular system. The aim of this paper was to present complex clinical picture of the syndrome and its variable expression on the example of the family diagnosed genetically on the neonatal ward, after proband’s prenatal examination. Maretial and methods: Nine family members were tested for TBX5 gene mutation. Results: Four of family members were diagnosed with Holt-Oram syndrome and five had correct genetic test results. The diagnosis allowed to identify a genetic risk family and enabled to provide them with genetic counselling. Conclusions: Diagnosis of Holt-Oram syndrome is possible as early as in prenatal period and it can be verified by genetic tests

Aberracje chromosomowe jako przyczyna poronień samoistnych

The genetic factor remains the most frequent cause of spontaneous abortions. Examination of the fetal tissue from spontaneous miscarriages shows that 75% of them were caused by abnormal karyotype. Other reasons, albeit rare, included submicroscopic genomic rearrangements, monogenic diseases, and polygenic inheritance disorders of the embryo. Objective: The aim of the study was to analyze the incidence of chromosomal aberrations in material from the miscarriage. Material and methods: The study included 47 samples of miscarriage material from 47 women. Fluorescent hybridization in-situ (FISH) was used for genetic examination. Results: Chromosomal abnormalities were diagnosed in 72% of the samples, with trisomy 21 (25.5%), trisomy 16 (17%), and trisomy 18 (12.8 %) as the most common. An abnormal number of copies of chromosome 18,21,22, indicating the coexistence of trisomy 18,21,22, was detected in 1 patient. It was another miscarriage in case of 14 subjects (29.8%). Conclusions: Chromosomal aberrations were diagnosed in the majority of fetal tissue samples from spontaneous miscarriages. More than one chromosomal aberration in a single embryo is an extremely rare occurrence. Miscarriage due to chromosomal aberrations occurred in the vast majority of women >35 years of age.Jedną z najczęstszych przyczyn poronień samoistnych jest czynnik genetyczny. W badaniu techniką mikromacierzy stwierdzono, że około 75% poronionych zarodków miało aberrację chromosomową. Rzadszymi przyczynami mogą być submikroskopowe rearanżacje genomowe, choroby jednogenowe, choroby zarodka dziedziczone wielogenowo. Cel pracy: Celem pracy była analiza częstości występowania aberracji chromosomowych w materiale z poronień. Materiał i metody: Materiał stanowiło 47 kosmówek z poronień samoistnych od 47 kobiet. Do oznaczenia kariotypu zastosowano metodę fluorescencyjnej hybrydyzacji in situ (FISH). Wyniki: Aberracje chromosomowe rozpoznano w 72% kosmówek. Najczęściej wystąpiła trisomia 21 pary (25,5%), trisomia 16 pary (17%), trisomia 18 pary (12,8%). U 1 pacjentki wykryto nieprawidłową liczbę kopii chromosomu 18,21,22, co wskazuje na współistnienie trisomii 18,21,22. U 14 kobiet (29,8%)t było to kolejne poronienie. Wnioski: Aberracje chromosomowe rozpoznano w większości kosmówek uzyskanych z poronień samoistnych. Bardzo rzadko występuje kilka aberracji chromosomowych w jednym zarodku. W grupie wiekowej kobiet powyżej 35 roku życia poronienia były skutkiem aberracji chromosomowych w znaczącej większości

Ocena genotypów wirusów brodawczaka ludzkiego u kobiet z nieprawidłową cytologią

Objective: To assess presence of HPV infection and identification of the most common HPV types in patients with abnormal cytology based on the Bethesda system (atypical squamous cells). Material and method: 81 women with abnormal cytology based on the Bethesda system (atypical squamous cells) were qualified for the study. Material was taken from the cervical canal, the vaginal portion of the cervix and the vagina onto a liquid medium to detect HPV DNA and genotyping of 19 most common oncogenic types of high and medium risk was performed with the Papillomastrip method and for HPV types 6 and 11 with the PCR method. Results: HPV was detected in 53 out of 81 examined women, which accounted for 66%. The most common HPV types were: 6/11 – 23 cases (43% of women with infection), 16 – 23 cases (43% of women with infection), 18 and 33 with 9 cases each (17% of women with infection). Coexistence of 6/11 with 16 or 18 – 13 concerned 15 patients (28% of women with infection) and presence of HPV 16 or 18 was detected in 28 cases (53% of women with infection). Positive HPV type contained in the quadrivalent vaccine against human papillomavirus 6/11 and 16 or 18 was detected in 38 patients (72% of women with infection). 40% of HPV positive women were infected with only one type of the virus, 26% - with two types and 23% with three types. Conclusion: In 81 women with abnormal cytology based on the Bethesda system (atypical squamous cells) within 66% of HPV positive results the most common were type 6/11 (of low oncogenic potential but responsible for anogenital warts) and type 16 of high oncogenic potential.Cel pracy: Ocena obecności zakażenia HPV (Human Papilloma Virus) i identyfikacja najczęściej występujących typów HPV u pacjentek z nieprawidłowym wynikiem cytologii (nieprawidłowości komórek nabłonka płaskiego – wg klasyfikacji Bethesda). Materiał i metoda: Do badań zakwalifikowano 81 pacjentek z nieprawidłowym wynikiem badania cytologicznego wg systemu Bethesda (nieprawidłowości komórek nabłonka płaskiego). Materiał w postaci wymazu z kanału i tarczy szyjki macicy i pochwy pobierano szczoteczką typu cytobrush na płynne medium na obecność DNA HPV z genotypowaniem najczęściej spotykanych 19 typów onkogennych wysokiego i średniego ryzyka i oznaczano metodą Papillomastrip oraz typów 6 i 11 HPV – metodą PCR. Wyniki: Spośród 81 przebadanych pacjentek HPV stwierdzono u 53 kobiet, co stanowiło 66%. Najczęściej występujące typy HPV: 6/11 i 16 - 23 przypadki (43% w grupie kobiet z infekcją), 18 i 33 – 9 przypadków w obu typach (17% kobiet z infekcją). Współistnienie 6/11 z typem 16 lub 18 dotyczyło 15 pacjentek (28% kobiet z infekcją). Łącznie, występowanie HPV 16 lub 18 to 28 pacjentek (53% kobiet z infekcją). U 38 pacjentek (72% kobiet z infekcją) wykazano współwystępowanie HPV 6/11 i 16 lub 18, zawarte w czterowalentnej szczepionce przeciw wirusowi ludzkiego brodawczaka. U 40% kobiet HPV dodatnich stwierdzono zakażenie tylko jednym typem wirusa, 26% – dwoma typami, a 23% 3 typami. Wnioski: W badanej grupie 81 kobiet z nieprawidłową cytologią (nieprawidłowości komórek nabłonka płaskiego – wg klasyfikacji Bethesda) spośród 66% (53 kobiety) dodatnich wyników na obecność HPV najczęściej wykrywano typy 6/11 – 23 przypadki (co stanowi 43%) – o małym potencjale onkogennym ale odpowiedzialnym za występowanie kłykcin kończystych okolic anogenitalnych) i typ 16, również 23 przypadki (43%) o wysokim potencjale onkogennym

Accuracy of congenital anomaly coding in live birth children recorded in European health care databases, a EUROlinkCAT study

Electronic health care databases are increasingly being used to investigate the epidemiology of congenital anomalies (CAs) although there are concerns about their accuracy. The EUROlinkCAT project linked data from eleven EUROCAT registries to electronic hospital databases. The coding of CAs in electronic hospital databases was compared to the (gold standard) codes in the EUROCAT registries. For birth years 2010–2014 all linked live birth CA cases and all children identified in the hospital databases with a CA code were analysed. Registries calculated sensitivity and Positive Predictive Value (PPV) for 17 selected CAs. Pooled estimates for sensitivity and PPV were then calculated for each anomaly using random effects meta-analyses. Most registries linked more than 85% of their cases to hospital data. Gastroschisis, cleft lip with or without cleft palate and Down syndrome were recorded in hospital databases with high accuracy (sensitivity and PPV ≥ 85%). Hypoplastic left heart syndrome, spina bifida, Hirschsprung’s disease, omphalocele and cleft palate showed high sensitivity (≥ 85%), but low or heterogeneous PPV, indicating that hospital data was complete but may contain false positives. The remaining anomaly subgroups in our study, showed low or heterogeneous sensitivity and PPV, indicating that the information in the hospital database was incomplete and of variable validity. Electronic health care databases cannot replace CA registries, although they can be used as an additional ascertainment source for CA registries. CA registries are still the most appropriate data source to study the epidemiology of CAs

COVID-19 and children with congenital anomalies:a European survey of parents' experiences of healthcare services

Objective: To survey parents and carers of children with a congenital anomaly across Europe about their experiences of healthcare services and support during the COVID-19 pandemic. Design: Cross-sectional study. Setting: Online survey in 10 European countries, open from 8 March 2021 to 14 July 2021. Population: 1070 parents and carers of children aged 0-10 years with a cleft lip, spina bifida, congenital heart defect (CHD) requiring surgery and/or Down syndrome. Main outcome measures: Parental views about: the provision of care for their child (cancellation/postponement of appointments, virtual appointments, access to medication), the impact of disruptions to healthcare on their child's health and well-being, and satisfaction with support from medical sources, organisations and close relationships. Results: Disruptions to healthcare appointments were significantly higher (p<0.001) in the UK and Poland, with approximately two-thirds of participants reporting â € cancelled or postponed' tests (67/101; 256/389) and procedures compared with approximately 20% in Germany (13/74) and Belgium/Netherlands (11/55). A third of participants in the UK and Poland reported â € cancelled or postponed' surgeries (22/72; 98/266) compared with only 8% in Germany (5/64). In Poland, 43% (136/314) of parents reported that changes to their child's ongoing treatment had moderately to severely affected their child's health, significantly higher than all other countries (p<0.001). Satisfaction ratings for support from general practitioners were lowest in the UK and Poland, and lowest in Poland and Italy for specialist doctors and nurses. Conclusion: A large proportion of participants reported disruptions to healthcare during the pandemic, which for some had a significant impact on their child's health. Regional differences in disruptions raise questions about the competence of certain healthcare systems to meet the needs of this vulnerable group of patients and indicate improvements should be strived for in some regions

Isolated brachydactyly type E caused by a HOXD13 nonsense mutation: a case report

<p>Abstract</p> <p>Background</p> <p>Brachydactyly type E (BDE; MIM#113300) is characterized by shortening of the metacarpal, metatarsal, and often phalangeal bones, and predominantly affects postaxial ray(s) of the limb. BDE may occur as an isolated trait or as part of a syndrome. Isolated BDE is rare and in the majority of cases the molecular pathogenesis has so far not been resolved. Originally, the molecular cause of isolated BDE has been unravelled in 2 families and shown to result from heterozygous missense mutations in the homeodomain of the <it>HOXD13 </it>gene. Since the initial manuscript, one further <it>HOXD13 </it>mutation has been reported only in a single family manifesting isolated BDE.</p> <p>Case Presentation</p> <p>In this paper, we report on a Polish family exhibiting isolated BDE caused by a novel nonsense heterozygous <it>HOXD13 </it>mutation. We investigated a Polish female proband and her father, both affected by isolated BDE, in whom we identified a nonsense heterozygous mutation c.820C > T(p.R274X) in the <it>HOXD13 </it>gene. So far, only two missense <it>HOXD13 </it>substitutions (p.S308C and p.I314L), localized within the homeodomain of the HOXD13 transcription factor, as well as a single nonsense mutation (p.E181X) were associated with BDE. Both missense changes were supposed to alter DNA binding affinity of the protein.</p> <p>Conclusion</p> <p>The variant p.R274X identified in our proband is the fourth <it>HOXD13 </it>mutation, and the second truncating (nonsense) mutation, reported to result in typical isolated BDE. We refer our clinical and molecular findings to the previously described <it>HOXD13 </it>associated phenotypes and mutations.</p

Ocena prawdopodobieństwa wystąpienia różnych patologii ciąży w rodzinach nosicieli translokacji chromosomowych wzajemnych angażujących chromosom 20

Carriership of reciprocal chromosome translocation (RCT) in a family may be the reason for malformation at birth, stillbirth, early neonatal death, and miscarriage due to unbalanced karyotype (monosomy/trisomy). The size of chromosome segments determined by the breakpoint position, kind of chromosome involved and the carrier’s gender may influence the probability rate for each category of the unfavorable pregnancy outcome in the family of the carrier of a particular RCT. Until now, the literature lacks reports on the risk values for particular forms of pregnancy outcomes in case of single segment imbalance, both the short (p) and the long arm (q) of chromosome 20. Objective: The aim of the study was to evaluate individual risk rates for unbalanced offspring at birth for single segment imbalance in the form of trisomy/monosomy and a separate evaluation risk figures for different pregnancy outcomes, depending on the size of the involved chromosome segment, its origin and carrier gender in families of RCT carriers involving chromosome 20 (RCT-20). In addition, practical application of the obtained results in the family with unique RCT t(13;20)(q14.1;p11.21) carriership has been shown. Material and methods: Total empirical data of 50 families (219 pregnancies) were collected from 19 pedigrees of RCT-20 carriers coming from different collections of RCT and available references. Cytogenetic studies were performed by GTG technique. The probability rates of particular type of pathology related to the total number of pregnancies after ascertainment correction have been done by segregation analysis according to the method of Stengel-Rutkowski and Stene. Results: The probability rate for unbalanced offspring at birth for carriers of RCT-20p was calculated as 5.5±1.8% (9/164) (medium risk). Considering parental gender of the carrier for maternal (MAT) and paternal (PAT) carriers, the probability rate values were similar i.e. 4.8±2.3% (4/84) and 4.9±2.8% (3/61), respectively. The risk figures for stillbirth/ early neonatal deaths were found as 0.6±0.6% (1/164) (low risk), but separately for MAT and PAT carriers they were: 1.2±1.2% (1/84) andNosicielstwo translokacji chromosomowej wzajemnej (TCW) w rodzinie może prowadzić do urodzenia potomstwa z wadami rozwojowymi, bądź być przyczyną wystąpienia różnych form patologii ciąży wywołanych niezrównoważonym kariotypem (monosomią/trisomią). Wielkość segmentów wyznaczonych przez położenie punktu złamania i rodzaj zaangażowanego chromosomu oraz płeć nosiciela wpływają na wielkość prawdopodobieństwa wystąpienia każdej z form patologii ciąży w rodzinie nosiciela danej TCW. Jak dotąd nie jest znana wielkość tych wskaźników w przypadku niezrównoważenia pojedynczego segmentu chromosomowego zarówno dla krótkiego (p) jak i długiego (q) ramienia chromosomu 20. Cel pracy: Celem badań było opracowanie indywidualnych wskaźników prawdopodobieństwa urodzenia dziecka z niezrównoważonym kariotypem na skutek monosomii/trisomii pojedynczego segmentu chromosomowego oraz wskaźników ryzyka wystąpienia poszczególnych patologii ciąży w zależności od wielkości segmentu i jego pochodzenia oraz płci nosiciela w rodzinach nosicieli TCW angażujących chromosom 20 (TCW-20). Zastosowanie uzyskanych wyników do opracowania porady genetycznej w rodzinie z nosicielstwem unikatowej translokacji t(13;20) (q14.1; p11.21) jako przykład ich praktycznego wykorzystania. Materiał i metody: Dane empiryczne i cytogenetyczne o 219 ciążach 50 nosicieli uzyskano z 19 rodowodów. Wielkość wskaźników opracowano metodą Stengel-Rutkowski z korektą oszacowania wg Stene. Wyniki: Prawdopodobieństwo urodzenia dziecka z niezrównoważonym kariotypem w rodzinach nosicieli TCW -20p wynosi: 5,5±1,8% (9/164), w tym w przypadku nosicielstwa matczynego 4,8±2,3% (4/84), a ojcowskiego 4,9±2,8% (3/61), natomiast w rodzinach nosicieli TCW-20q ok. 2,6% (0/20). Ryzyko wystąpienia ciąży obumarłej/wczesnego zgonu noworodka w rodzinach nosicieli TCW-20p szacuje się na 0,6±0,6% (1/164), natomiast nosicieli TCW-20q na ok. 2,6% (0/20). Ryzyko wystąpienia poronień samoistnych wynosi odpowiednio: 28,6±3,5% (47/164) i 50±11,2% (10/20). Wnioski: 1. Wskaźniki prawdopodobieństwa urodzenia dziecka z niezrównoważonym kariotypem, jak też wskaźniki ryzyka wystąpienia badanych form patologii ciąży wykazują różnice w zależności od pochodzenia i wielkości segmentu chromosomu 20. 2. Nie stwierdzono różnic w wielkości poszczególnych wskaźników w zależności od płci nosiciela