Endemic parkinsonism: clusters, biology and clinical features.

The term 'endemic parkinsonism' refers to diseases that manifest with a dominant parkinsonian syndrome, which can be typical or atypical, and are present only in a particular geographically defined location or population. Ten phenotypes of endemic parkinsonism are currently known: three in the Western Pacific region; two in the Asian-Oceanic region; one in the Caribbean islands of Guadeloupe and Martinique; and four in Europe. Some of these disease entities seem to be disappearing over time and therefore are probably triggered by unique environmental factors. By contrast, other types persist because they are exclusively genetically determined. Given the geographical clustering and potential overlap in biological and clinical features of these exceptionally interesting diseases, this Review provides a historical reference text and offers current perspectives on each of the 10 phenotypes of endemic parkinsonism. Knowledge obtained from the study of these disease entities supports the hypothesis that both genetic and environmental factors contribute to the development of neurodegenerative diseases, not only in endemic parkinsonism but also in general. At the same time, this understanding suggests useful directions for further research in this area.

Prenatal detection of copy number variants in fetuses with detected congenital devolpmental disordes, from 2015 to 2020 by Multiplex Ligation-Dependent Probe Amplification and microarray analysis.

OBJECTIVE: Analysis of prenatal samples from 2015 to 2020. Comparison detection rates of clinically relevant variants by cytogenetic karyotype analysis and cytogenomic MLPA (Multiplex Ligation-Depent Probe Amplification) and microarray methods (CMA - chromosomal microarray). MATERIAL AND METHOD: 1,029 prenatal samples were analyzed by cytogenetic karyotyping (N = 1,029), cytogenomic methods - MLPA (N = 144) and CMA (N = 111). All unbalanced changes were confirmed by MLPA or CMA. RESULTS: From the analyzed set of fetuses, after subtraction of aneuploidies - 107 (10.40%, N = 1,029), 22 structural aberrations (2.39%, N = 922) - nine unbalanced changes (0.98%), 10 balanced changes (1.08%), one case of unclear mosaicism (0.09%), one case of presence of a marker chromosome (0.09%) and one case of sex discordance (0.09%) - were detected by karyotype analysis. A total of eight (7.21%, N = 111) pathological variants were detected by CMA in 255 samples with physiological karyotype indicated for cytogenomic examination. Five (3.47%, N = 144) of eight pathogenic variants were detected by MLPA method. The total capture of pathogenic variants by MLPA and CMA methods was 14 (5.14%) and 17 (6.25%) (N = 272), including confirmatory pathological karyotype testing. Detection of pathological variants in the isolated disorders group was lower than in the multiple disorders group (5.08 vs. 21.42%). CONCLUSION: A higher success rate for the detection of pathological copy number variation variants by the microarray method than by the MLPA method was confirmed.

Karyotyping of Lymphocytes and Epithelial Cells of Distinct Embryonic Origin Does Not Help to Predict the Turner Syndrome Features.

BACKGROUND: In Turner syndrome (TS), fluorescent in situ hybridization (FISH) karyotyping offers an alternative to classical karyotyping. OBJECTIVE: We tested the added value of FISH karyotyping from lymphocytes (mesodermal origin), buccal cells (ectodermal origin), and a rear-tongue smear (endodermal origin) to determine the 45,X cell line fraction and its impact on patient phenotype. DESIGN AND PATIENTS: Classical karyotyping and three FISH assays were done in 153 girls and women previously diagnosed with TS in four university hospitals. The 45,X cell line fraction was determined for each method and correlated with the major phenotypic signs. RESULTS: Classical karyotyping identified 45,X/46,XX mosaicism in 77/153 subjects (50%), 45,X monosomy in 52/153 (34%), and other karyotypes in 24/153 (16%). FISH from lymphocytes verified 45,X in 47/52 original cases, whereas 4/52 had 45,X/46,XX and 1/52 45,X/47,XYY mosaicism. The 45,X cell line fraction was higher in FISH from lymphocytes compared to classical karyotyping (median 86.4% vs. 70.0%; p < 0.001), while there was no difference for FISH from buccal or rear-tongue smear cells. The mean 45,X cell line fraction was more abundant in patients with several of the characteristic phenotypic signs compared to patients without them (p < 0.01), but the predictive power was insufficient. CONCLUSION: FISH analysis confirmed the findings of classical karyotyping; only a few 45,X monosomy cases were reclassified as mosaics. The 45,X cell line fraction did not show clinically meaningful prediction of the phenotype. FISH analysis of buccal or rear-tongue epithelial cells may be a non-inferior, less invasive alternative to classical karyotyping.

Ovarian tumors and genetic predisposition.

OBJECTIVE: Summary of knowledge in the field of ovarian cancer and genetic predisposition. RESULTS: Ovarian tumors are usually diagnosed at advanced stages of the disease and the prognosis for these patients is generally poor. The 5-year overall survival rate, regardless of the histopathological type of tumor, is around 44%. Germline mutations causing hereditary tumor syndromes are predominantly involved in the development of epithelial ovarian tumors. The most common is hereditary breast and ovarian cancer syndrome, which is caused by germline mutations in the tumor suppressor genes BRCA1 and BRCA2. Several other tumor suppressor genes and oncogenes are known to be associated with ovarian tumors and cause other types of tumor syndromes. Inherited tumor syndromes include Lynch syndrome, Peutz-Jegers syndrome, Gorlin syndrome, Li-Fraumeni syndrome and others. The indication for genetic examination of germline mutations is given by a clinical geneticist on the basis of the recommendation of the attending physician. At present, every ovarian tumor, primary peritoneal tumor and tube tumor diagnosed at any age is indicated for genetic testing. CONCLUSION: Early identification of genes for hereditary cancer syndromes, thanks to rapidly developing molecular genetic methods, is an important step towards personalized treatment of ovarian cancer and preventive measures in families at risk. It is also important to note that a negative molecular genetic test result does not exclude genetic risk.

Detection of Unknown and Rare Pathogenic Variants in Antithrombin, Protein C and Protein S Deficiency Using High-Throughput Targeted Sequencing.

The deficiency of natural anticoagulants­antithrombin (AT), protein C (PC), and protein S (PS)­is a highly predisposing factor for thrombosis, which is still underdiagnosed at the genetic level. We aimed to establish and evaluate an optimal diagnostic approach based on a high-throughput sequencing platform suitable for testing a small number of genes. A fast, flexible, and efficient method involving automated amplicon library preparation and target sequencing on the Ion Torrent platform was optimized. The cohort consisted of a group of 31 unrelated patients selected for sequencing due to repeatedly low levels of one of the anticoagulant proteins (11 AT-deficient, 13 PC-deficient, and 7 PS-deficient patients). The overall mutation detection rate was 67.7%, highest in PC deficiency (76.9%), and six variants were newly detected­SERPINC1 c.398A > T (p.Gln133Leu), PROC c.450C > A (p.Tyr150Ter), c.715G > C (p.Gly239Arg) and c.866C > G (p.Pro289Arg), and PROS1 c.1468delA (p.Ile490fs) and c.1931T > A (p.Ile644Asn). Our data are consistent with those of previous studies, which mostly used time-consuming Sanger sequencing for genotyping, and the indication criteria for molecular genetic testing were adapted to this process in the past. Our promising results allow for a wider application of the described methodology in clinical practice, which will enable a suitable expansion of the group of indicated patients to include individuals with severe clinical findings of thrombosis at a young age. Moreover, this approach is flexible and applicable to other oligogenic panels.

Whole Exome Sequencing Study in Isolated South-Eastern Moravia (Czechia) Population Indicates Heterogenous Genetic Background for Parkinsonism Development.

Parkinsonism belongs to the most common neurodegenerative disease. Genetic predisposition could be one of the significant risk factor for disease development. It has been described higher prevalence of parkinsonism in large pedigree from southeastern Moravia region. The study aims were to select accessible subfamily trios from the pedigree suitable for segregation genetic analyses to perform whole exome sequencing (WES) in trio individuals and further to evaluate genetic variants in the each trio. We used IonTorrent platform for WES for five subfamily trios (1-5). Each trio included two affected and one healthy person (as control). Found variants were filtered with respect to MAF < 1% (minor allele frequency), variants effect (based on prediction tools) and disease filter (Parkinsonism responsible genes). Finally, the variants from each trio were assessed with respect to the presence in the patients. There were found no one founder mutation in the subfamilies from the pedigree. Trio 1 shares two variants with trio 2:MC1R:c.322G > A (p.A108T) and MTCL1:c.1445C > T (p.A482V), trio 3 shares two variants with trio 5: DNAJC6:c.1817A > C (p.H606P) and HIVEP3:c.3856C > A (p.R1286W). In trios 4 and 5, there were found two variants in gene CSMD1:c.3335A > G (p.E1112G) and c.4071C > G (p.I1357M) respectively. As the most potentially damaging, we evaluated the non-shared variant SLC18A2:c.583G > A (p.G195S). The variant could affect dopamine transport in dopaminergic neurons. The study of the parkinsonism genetic background in isolated Moravian population suggested that there could be significant accumulation of many risk genetic factors. For verification of the variants influence, it would be appropriate to perform a more extensive population study and suitable functional analysis.

Lewy body disease or diseases with Lewy bodies?

The current nosological concept of α-synucleinopathies characterized by the presence of Lewy bodies (LBs) includes Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB), for which the term "Lewy body disease" (LBD) has recently been proposed due to their considerable clinical and pathological overlap. However, even this term does not seem to describe the true nature of this group of diseases. The subsequent discoveries of α-synuclein (αSyn), SNCA gene, and the introduction of new immunohistochemical methods have started intensive research into the molecular-biological aspects of these diseases. In light of today's knowledge, the role of LBs in the pathogenesis and classification of these nosological entities remains somewhat uncertain. An increasingly more important role is attributed to other factors as the presence of various LBs precursors, post-translational αSyn modifications, various αSyn strains, the deposition of other pathological proteins (particularly ß-amyloid), and the discovery of selective vulnerability of specific cells due to anatomical configuration or synaptic dysfunction. Resulting genetic inputs can undoubtedly be considered as the main essence of these factors. Molecular-genetic data indicate that not only in PD but also in DLB, a unique genetic architecture can be ascertained, predisposing to the development of specific disease phenotypes. The presence of LBs thus remains only a kind of link between these disorders, and the term "diseases with Lewy bodies" therefore results somewhat more accurate.

High-Throughput Sequencing Haplotype Analysis Indicates in LRRK2 Gene a Potential Risk Factor for Endemic Parkinsonism in Southeastern Moravia, Czech Republic.

Parkinson's disease and parkinsonism are relatively common neurodegenerative disorders. This study aimed to assess potential genetic risk factors of haplotypes in genes associated with parkinsonism in a population in which endemic parkinsonism and atypical parkinsonism have recently been found. The genes ADH1C, EIF4G1, FBXO7, GBA, GIGYF2, HTRA2, LRRK2, MAPT, PARK2, PARK7, PINK1 PLA2G6, SNCA, UCHL1, and VPS35 were analyzed in 62 patients (P) and 69 age-matched controls from the researched area (C1). Variants were acquired by high-throughput sequencing using Ion Torrent workflow. As another set of controls, the whole genome sequencing data from 100 healthy non-related individuals from the Czech population were used (C2); the results were also compared with the Genome Project data (C3). We observed shared findings of four intron (rs11564187, rs36220738, rs200829235, and rs3789329) and one exon variant (rs33995883) in the LRRK2 gene in six patients. A comparison of the C1-C3 groups revealed significant differences in haplotype frequencies between ratio of 2.09 for C1, 1.65 for C2, and 6.3 for C3, and odds ratios of 13.15 for C1, 2.58 for C2, and 7.6 for C3 were estimated. The co-occurrence of five variants in the LRRK2 gene (very probably in haplotype) could be an important potential risk factor for the development of parkinsonism, even outside the recently described pedigrees in the researched area where endemic parkinsonism is present.

Haplotype analysis of the X chromosome in patients with Turner syndrome in order to verify the possible effect of imprinting on selected symptoms.

AIMS: Turner syndrome is the only chromosome monosomy that is postnatally compatible with life. The reported incidence of TS is 1 in 2500 liveborn girls. The phenotype of these girls is highly variable, with cardiac abnormalities being life-threatening defects. The aim of the study was to reveal the possible influence of the parental origin of the X chromosome in these patients on a selected phenotype that is associated with Turner syndrome. Selected symptoms and parameters were: a bicuspid aortic valve, aortic coarctation, lymphoedema, pterygium colli, coeliac disease, thyroiditis, otitis media, diabetes mellitus 2, renal abnormalities, spontaneous puberty, and IVF. METHODS: The X chromosome haplotype was determined for a group of 45,X patients verified by native FISH. A molecular diagnostic method based on the detection of different lengths of X chromosome-linked STR markers using the Argus X-12 QS kit was used to determine the X haplotype. RESULTS: Our results, analysed by Fisher's exact (factorial) test, suggest independence between the maternal/paternal origin of the inherited X chromosome and the presence of the anomalies that were studied (P=1 to P=0.34). CONCLUSION: In the group of 45,X patients, who were precisely selected by means of the native FISH method, no correlation was demonstrated with the parental origin of the X chromosome and the observed symptom.

MLPA analysis of 32 foetuses with a congenital heart defect and 1 foetus with renal defects - pilot study. The significant frequency rate of presented pathological CNV.

AIMS: The aim of this retrospective study was to determine the detection rate of the pathogenic copy number variants (CNVs) in a cohort of 33 foetuses - 32 with CHD (congenital heart defects) and 1 with kidney defect, after exclusion of common aneuploidies (trisomy 13, 18, 21, and monosomy X) by karyotyping, Multiplex ligation - dependent probe amplification (MLPA) and chromosomal microarray analysis (CMA). We also assess the effectivity of MLPA as a method of the first tier for quick and inexpensive detection of mutations, causing congenital malformations in foetuses. METHODS: MLPA with probe mixes P070, P036 - Telomere 3 and 5, P245 - microdeletions, P250 - DiGeorge syndrome, and P311 - CHD (Congenital heart defects) was performed in 33 samples of amniotic fluid and chorionic villi. CMA was performed in 10 relevant cases. RESULTS: Pathogenic CNVs were found in 5 samples: microdeletions in region 22q11.2 (≈2 Mb) in two foetuses, one distal microdeletion of the 22q11.2 region containing genes LZTR1, CRKL, AIFM3 and SNAP29 (≈416 kb) in the foetus with bilateral renal agenesis, 8p23.1 (3.8 Mb) microdeletion syndrome and microdeletion in area 9q34.3 (1.7 Mb, Kleefstra syndrome). MLPA as an initial screening method revealed unambiguously pathogenic CNVs in 15.2 % of samples. CONCLUSION: Our study suggests that MLPA and CMA are a reliable and high-resolution technology and should be used as the first-tier test for prenatal diagnosis of congenital heart disease. Determination of the cause of the abnormality is crucial for genetic counselling and further management of the pregnancy.

Quality of life and sexuality in women with urinary incontinence.

OBJECTIVE: An overview of urinary incontinence and the associated quality of life in women, including sexuality. METHODS: Compilation of published data from scientific literature. CONCLUSION: Urinary incontinence and female sexual dysfunction are common problems that adversely affect a womans quality of life. Their cause is often multifactorial. Both of these dysfunctions are common in women, but are often not reported by them and, subsequently,  not treated. The symptoms of urinary incontinence, shame and fear can lead to complete social isolation of a woman affected in this way. There are a lot of studies suggesting that coping with a urination problem can subsequently improve a womans sexual function and overall quality of life. The prevalence increases significantly with the age.

Risk Minimization of Hemolytic Disease of the Fetus and Newborn Using Droplet Digital PCR Method for Accurate Fetal Genotype Assessment of RHD, KEL, and RHCE from Cell-Free Fetal DNA of Maternal Plasma.

The molecular pathology of hemolytic disease of the fetus and newborn (HDFN) is determined by different RHD, RHCE, and KEL genotypes and by blood group incompatibility between the mother and fetus that is caused by erythrocyte antigen presence/absence on the cell surface. In the Czech Republic, clinically significant antierythrocyte alloantibodies include anti-D, anti-K, anti C/c, and anti-E. Deletion of the RHD gene and then three single nucleotide polymorphisms in the RHCE and KEL genes (rs676785, rs609320, and rs8176058) are the most common. The aim of this study is to develop effective and precise monitoring of fetal genotypes from maternal plasma of these polymorphisms using droplet digital (dd)PCR. Fifty-three plasma DNA samples (from 10 to 18 weeks of gestation) were analyzed (10 RHD, 33 RHCE, and 10 KEL). The ddPCR methodology was validated on the basis of the already elaborated and established method of minisequencing and real-time PCR and with newborn phenotype confirmation. The results of ddPCR were in 100% agreement with minisequencing and real-time PCR and also with newborn phenotype. ddPCR can fully replace the reliable but more time-consuming method of minisequencing and real-time PCR RHD examination. Accurate and rapid noninvasive fetal genotyping minimizes the possibility of HDFN developing.

Duplication of 9p24.3 in three unrelated patients and their phenotypes, considering affected genes, and similar recurrent variants.

BACKGROUND: Recent studies suggest that duplication of the 9p24.3 chromosomal locus, which includes the DOCK8 and KANK1 genes, is associated with autism spectrum disorders (ASD), intellectual disability/developmental delay (ID/DD), learning problems, language disorders, hyperactivity, and epilepsy. Correlation between this duplication and the carrier phenotype needs further discussion. METHODS: In this study, three unrelated patients with ID/DD and ASD underwent SNP aCGH and MLPA testing. Similarities in the phenotypes of patients with 9p24.3, 15q11.2, and 16p11.2 duplications were also observed. RESULTS: All patients with ID/DD and ASD carried the 9p24.3 duplication and showed intragenic duplication of DOCK8. Additionally, two patients had ADHD, one was hearing impaired and obese, and one had macrocephaly. Inheritance of the 9p24.3 duplication was confirmed in one patient and his sibling. In one patient KANK1 was duplicated along with DOCK8. Carriers of 9p24.3, 15q11.2, and 16p11.2 duplications showed several phenotypic similarities, with ID/DD more strongly associated with duplication of 9p24.3 than of 15q11.2 and 16p11.2. CONCLUSION: We concluded that 9p24.3 is a likely cause of ASD and ID/DD, especially in cases of DOCK8 intragenic duplication. DOCK8 is a likely causative gene, and KANK1 aberrations a modulator, of the clinical phenotype observed. Other modulators were not excluded.

Fetal heart rhabdomyomatosis: a single-center experience.

Objectives: The primary aim of the study was to evaluate the prevalence of fetal heart tumors in a single tertiary referral center over a period of 15 years. The secondary aim was to confirm the presence of tuberous sclerosis complex (TSC) through the evaluation of germline mutation in TSC1/TSC2 and assess the outcomes in affected fetuses and newborns.Methods: A retrospective study was conducted between 2003 and 2017. Fetal echocardiography was performed in the second trimester of pregnancy in the study population. The identification of heart tumors and further follow-up were performed by a pediatric cardiologist. Molecular genetic analysis was conducted on fetuses and children in cases where TSC was suspected.Results: In total, 39,018 fetuses were examined between 2003 and 2017. Heart tumors were detected in nine fetuses and were diagnosed as rhabdomyoma in all cases. We identified mutations in one of the TSC1 or TSC2 genes in all cases with multiple rhabdomyomas (8/9). In all born children (5/9), the genetically confirmed diagnosis of TSC was established, and clinically pathological deposits in the brain were found.Conclusion: Fetal heart tumors are usually represented by rhabdomyomas having a good cardiac prognosis. However, rhabdomyoma is usually the first symptom of TSC with a subsequent brain disorder and impaired neurological development.

Cytoplasmic Transfer Improves Human Egg Fertilization and Embryo Quality: an Evaluation of Sibling Oocytes in Women with Low Oocyte Quality.

The aim of this study was to evaluate if cytoplasmic transfer can improve fertilization and embryo quality of women with oocytes of low quality. During ICSI, 10-15% of the cytoplasm from a fresh or frozen young donor oocyte was added to the recipient oocyte. According to the embryo quality, we defined group A as patients in which the best embryo was evident after cytoplasmic transfer and group B as patients in which the best embryo was evident after a simple ICSI. We investigated in the period of 2002-2018, 125 in vitro fertilization cycles involving 1011 fertilized oocytes. Five hundred fifty-seven sibling oocytes were fertilized using ICSI only and 454 oocytes with cytoplasmic transfer. Fertilization rates of oocytes were 67.2% in the cytoplasmic transfer and 53.5% in the ICSI groups (P < 0.001). A reduction in fertilization rate was observed with increased women age in the ICSI but not in the cytoplasmic transfer groups. The best embryo quality was found after cytoplasmic transfer in 78 cycles (62.4%) and without cytoplasmic transfer in 40 cycles (32%, P < 0.001). No significant differences were detected between the age, hormonal levels, dose of stimulation drugs, number of transferred embryos, pregnancy rate and abortion rate between A and B groups. Cytoplasmic transfer improves fertilization rates and early embryo development in humans with low oocyte quality. All 28 children resulting from cytoplasmic transfer are healthy.

Desire for Parenthood and Associated Trends in Czech Lesbian Women.

INTRODUCTION: Worldwide, there are more lesbians who chose to have children in the context of a same-sex relationship than ever before. The Czech studies focusing on this issue, including the analysis of methods of conception, are limited. AIM: We aimed to examine the changes over time in the desire of Czech lesbian women for children and to analyze their chosen methods of conception. METHODS: We analyzed retrospectively the personal history of lesbian patients who visited our clinic in the period from 2009 to 2017. Our sample (n = 318) was divided into 2 groups: Group A - our patients between 2009 and 2013, whereas group B comprised our patients from 2013 to 2017. MAIN OUTCOME MEASURES: The outcome of this study is comparing groups A and B, regarding factors associated to parenthood, such as desire to have a child and preferences in methods of conception. RESULTS: We compared group A and group B and obtained the following results: The percentage of homosexual women who did not desire to have a child decreased (22.5% vs 15.6%). Regarding the changes in the preferences in methods of conception among group A and group B, the findings are as follows: a child from a previous relationship (31.2% vs 27.4%), clinically assisted reproduction with an anonymous donor (19.6% vs 30.1%), home intrauterine insemmination with a known donor (24.6% vs 19.2%), clinically assisted reproduction with a known donor (13.1% vs 9.6%), coitus outside the relationship for the purpose of a child conception (9.8% vs 5.5%), home intrauterine insemmination by sperm from an anonymous donor (1.6% vs 4.1%), assisted reproduction performed abroad was selected only in group B (2.7%). CONCLUSIONS: We confirm that the percentage of Czech lesbians who have a child or want to have a child has increased and that several variables regarding the desire for parenthood in the Czech lesbian community are changing over time (eg, methods of conception) mostly in concordance with other Western European countries. Turcan P, Prochazka M, Prochazka P, et al. Desire for Parenthood and Associated Trends in Czech Lesbian Women. Sex Med 2020;8:650-659.

Two Reliable Methodical Approaches for Non-Invasive RHD Genotyping of a Fetus from Maternal Plasma.

Noninvasive fetal RHD genotyping is an important tool for predicting RhD incompatibility between a pregnant woman and a fetus. This study aimed to assess a methodological approach other than the commonly used one for noninvasive fetal RHD genotyping on a representative set of RhD-negative pregnant women. The methodology must be accurate, reliable, and broadly available for implementation into routine clinical practice. A total of 337 RhD-negative pregnant women from the Czech Republic region were tested in this study. The fetal RHD genotype was assessed using two methods: real-time PCR and endpoint quantitative fluorescent (QF) PCR. We used exon-7-specific primers from the RHD gene, along with internal controls. Plasma samples were analyzed and measured in four/two parallel reactions to determine the accuracy of the RHD genotyping. The RHD genotype was verified using DNA analysis from a newborn buccal swab. Both methods showed an excellent ability to predict the RHD genotype. Real-time PCR achieved its greatest accuracy of 98.6% (97.1% sensitivity and 100% specificity (95% CI)) if all four PCRs were positive/negative. The QF PCR method also achieved its greatest accuracy of 99.4% (100% sensitivity and 98.6% specificity (95% CI)) if all the measurements were positive/negative. Both real-time PCR and QF PCR were reliable methods for precisely assessing the fetal RHD allele from the plasma of RhD-negative pregnant women.

Congenital fetal heart defect - an agreement between fetal echocardiography and autopsy findings.

AIMS: To determine the frequency of pregnancy terminations due to prenatal congenital heart defect (CHD) and assess the agreement fetal echocardiography (FECHO) and autopsy findings. METHODS: The data were retrospectively assessed between 2008 and 2017 in a population of 116 698 live births. The correlations between the FECHO and autopsy findings were classified into five levels of agreement: complete, partial, altered diagnosis, disagreement, and unfeasible autopsy. RESULTS: Totally, 293 CHDs were identified and 49% of families (143/293) decided to terminate the pregnancy. In 1% (2/143) of cases, the autopsy could not be performed, for the other 99% (141/143), the pathologist confirmed the presence of CHDs. Complete agreement between FECHO and autopsy was achieved in 85% (122/143). In 10% (14/143) of cases, the pathologist found minor findings, which were not described in the FECHO. In 4% (5/143) of cases, the pathologist changed the main diagnosis. CONCLUSION: Altogether, the results indicated that FECHO is a highly sensitive method for the prenatal detection of CHD but is incapable of detecting the complete spectrum of cardiac defects. Autopsies verified the diagnosis, confirmed the overall impairment in the fetus, and provided data for further counselling of the affected family.