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Primary cilia are a component of almost all vertebrate cells with a crucial role in sensing and transducing environmental signals during tissue development. Their dysfunction is known as ciliopathies and can manifest with a wide spectrum of clinical disorders. Overlapping features and molecular heterogeneity of ciliopathies make diagnoses distinctly challenging. In this group of diseases, tectonic genes, and their mutations play an important role. We present a first-trimester fetus with occipital encephalocele and OFD type IV caused by TCTN3 compound heterozygous pathogenic variants: c.1423_1429del (p.Arg475Serfs*10) and c.3G>A (initiator codon). A severe arm anomaly was described in our case, with two fingers along the atrophic forearm and polydactyly on other limbs. This could be a new phenotypic characteristic contributing to further understanding of TCTN3- related disorders as well as other tectonic proteins in ciliopathy spectrum diseases.

Objectives: The purpose of this study was to determine if elevated concentration of soluble receptor tunica interna endothelial cell kinase-2 (Tie-2) in the amniotic fluid represent a risk factor for the subsequent development of preeclampsia (PE). Study design: Amniotic fluid samples were collected as a part of routine clinical diagnostics from women referred to clinical care due to genetic indications. A total of 12 women with preeclampsia and 26 normotensive pregnant women were included in the study. Mean gestational age at amniocentesis was 17.92 weeks of pregnancy in preeclampsia and 17.88 in control group, respectively. Concentrations of sTie-2 in the amniotic fluid were determined by a standardized enzyme immunoassay. Results: Median concentration of Tie-2 in the amniotic fluid of PE patients was lower (median 1.109 ng/ml) compared with normotensive pregnant women (median 1.433 ng/Ml) but the difference was not statistically significant (p = 0.2973). Concentration of sTie-2 in the amniotic fluid did not significantly correlate with maternal age, gestational age at amniocentesis or delivery, as well as weight or length at birth. A difference in the gestational age at delivery in PE patients (mean 37.7 weeks) and normotensive pregnant controls (mean 39.8 weeks) was statistically significant (p = 0.0003). Birth weight and length of children delivered by PE women (mean 2863.3 g and 48.3 cm) were significantly lower compared with normal pregnancies (mean 3591.2 g and 51.4 cm, p = 0.0002 and p = 0.006, respectively). Conclusion: Our results suggest that amniotic fluid concentrations of sTie-2 do not predict development of PE and that further studies on biomarkers as predictors of PE should include other angiogenic biological response modifiers.

Objectives Approximately 90% of “XX males” are positive for SRY. However, there are isolated cases of sex reversal associated to other genes in male-determining pathway. Case presentation We describe a 1.3-old patient with 46,XX karyotype, male phenotypic gender and cryptorchidism. Microarray analysis revealed a de novo 273 kb duplication in the Xq27.1 region that contains SOX3. FISH with probe specific to SOX3 confirmed a unique genomic location of this duplication, dislocated proximal to the centromere of the X chromosome. Conclusions This rare genetic condition was described in few other isolated cases that have associated SOX3 genetic rearrangements and DSD. Microarray and genome-wide-sequencing presents important part in routine diagnostics, and in delineation of other sex-determination-pathway genes in sex reversal disorders.

Although the risk of pregnancy with Down syndrome (DS) increases with age, conceptions with trisomy 21 can occur in mothers aged 35 or less. The micronucleus test on peripheral blood lymphocytes is a well-recognized method for studying chromosomal instability. The aim of this study was to evaluate the application of the micronucleus assay and fluorescence in situ hybridization (FISH) for estimation of chromosome instability and occurrence of trisomy 21 in young parents having pregnancy or a child with the regular form of Down syndrome. The study included 54 parents (27 couples) who had previous pregnancy with trisomy 21 at age 35 or less. The control group consisted of 30 couples with two healthy children and no previous spontaneous abortions. Parents with trisomy 21 pregnancy had significantly higher frequencies of micronuclei in binucleated cells. There was no statistically significant difference between the study and control groups in the frequencies of micronuclei in mononuclear cells, nuclear buds, or nucleoplasmic bridges. FISH analysis showed higher percentages of micronuclei containing whole chromosomes as well as statistically significant higher numbers of micronuclei containing chromosome 21 in the peripheral blood of DS parents. There was no statistically significant difference between the two groups in the responses of peripheral blood lymphocytes to treatment with the mutagen mitomycin C. Our results suggest that young parents with a history of the regular form of Down syndrome have a higher susceptibility to chromosome nondisjunction in peripheral blood lymphocytes. The micronucleus assay showed high specificity, but moderate sensitivity, for risk assessment of trisomy 21 pregnancy.

Objective The aim of this study is to summarize the experience on prenatal diagnosis of Down syndrome. Materials and methods The study includes a retrospective data analysis of 157 prenatally detected cases of Down syndrome, routinely diagnosed among 6448 prenatal investigations performed during a 13-year period (2002–2014) in a single tertiary center. Results The prevalence of diagnosed Down syndrome cases was 2.4%. Maternal age alone was indication for prenatal diagnosis in 47 cases (45.2%), increased first-/second-trimester biochemical screening test in 34 cases (21.7%), abnormal ultrasound examination in 69 cases (43.9%), positive familial history for chromosomal abnormalities in four cases, and high risk for trisomy 21 revealed by cell-free DNA testing in three cases. Ultrasound anomalies were present in total of 94 fetuses (59.8%). The most common abnormality was cystic hygroma found in 46 cases (29.3%). A regular form of Down syndrome (trisomy 21) was found in 147 cases (93.6%), Robertsonian translocation in six cases (3.8%), and mosaic form in four cases (2.6%). Conclusion In prenatal diagnosis of Down syndrome noninvasive screening methods are important for estimation of individual risks, in both, young population of woman and older mothers, while conventional and molecular cytogenetic methods are essential for definite diagnosis and proper genetic counseling.

The aim of the study was to assess sleep architecture and breathing in sleep in children with Down syndrome. The study was conducted by using overnight video-polysomnography (V-PSG) in children with Down syndrome and age-matched children from the general population. Analysis of polysomnographic parameters revealed that compared to the norms of healthy age- and maturitymatched children from the general population, children with Down syndrome had significantly shorter sleep latency (p=0.007), shorter total sleep time (p=0.004), lower sleep efficiency (p=0.010), less NREM1 sleep phase (p=0.0002), less NREM3 sleep phase (p=0.034), less REM sleep (p=0.034) in favour of more NREM2 phase but not significantly (p=0.069), and spent more time awake after sleep onset (p=0.0002). Children with Down syndrome had significantly more obstructive sleep apnoeas and hypopnoeas per hour (higher obstructive sleep apnoeas and hypopnoeas index) (p=0.008), but less central sleep apnoea per hour (lower central apnoeas index) (p=0.041), which led to the nonsignificantly lower total apnoea- hypopnoea index (p=0.762) in children with Down syndrome. The mean and longest apnoea duration did not differ significantly between these two groups. Children with Down syndrome had a significantly lower mean and nadir oxygen saturation (p=0.008 and p=0.001, respectively). In conclusion, the majority of respiratory complications in children with Down syndrome can be prevented by raising awareness of sleep disturbances in children with Down syndrome among their parents and health care providers and by introducing early routine V-PSG in the follow up of these children.

The aim of the study was to assess sleep architecture and breathing in sleep in children with Down syndrome. The study was conducted by using overnight video-polysomnography (V-PSG) in children with Down syndrome and age-matched children from the general population. Analysis of polysomnographic parameters revealed that compared to the norms of healthy age- and maturitymatched children from the general population, children with Down syndrome had significantly shorter sleep latency (p=0.007), shorter total sleep time (p=0.004), lower sleep efficiency (p=0.010), less NREM1 sleep phase (p=0.0002), less NREM3 sleep phase (p=0.034), less REM sleep (p=0.034) in favour of more NREM2 phase but not significantly (p=0.069), and spent more time awake after sleep onset (p=0.0002). Children with Down syndrome had significantly more obstructive sleep apnoeas and hypopnoeas per hour (higher obstructive sleep apnoeas and hypopnoeas index) (p=0.008), but less central sleep apnoea per hour (lower central apnoeas index) (p=0.041), which led to the nonsignificantly lower total apnoea-hypopnoea index (p=0.762) in children with Down syndrome. The mean and longest apnoea duration did not differ significantly between these two groups. Children with Down syndrome had a significantly lower mean and nadir oxygen saturation (p=0.008 and p=0.001, respectively). In conclusion, the majority of respiratory complications in children with Down syndrome can be prevented by raising awareness of sleep disturbances in children with Down syndrome among their parents and health care providers and by introducing early routine V-PSG in the follow up of these children., Cilj: Istražiti arhitektoniku spavanja i disanja tijekom sna u djece s Downovim sindromom. Metode: Cjelonoćna videopolisomnografija (V-PSG) u skupini djece s Downovim sindromom i u onoj iz opće populacije odgovarajuće dobi i zrelosti. Rezultat: Analiza polisomnografskih parametara pokazala je da djeca s Downovim sindromom, u usporedbi s normativima u zdrave djece u općoj populaciji, odgovarajuće dobi i zrelosti, imaju značajno kraću latenciju spavanja (SL) p=0,007, kraće ukupno vrijeme spavanja (TST) p=0,004, nižu efikasnost spavanja (SE) p=0,010, manje NREM1 faze spavanja p=0,0002, manje NREM3 faze spavanja p=0,034, manje REM spavanja p= 0,034 (na račun više površnog NREM2 spavanja, ali ne statistički značajno, p=0,069) i da provode više vremena budni nakon započimanja spavanja (p=0,0002). Djeca s Downovim sindromom imaju značajno više opstruktivnih apneja i hipopneja po satu spavanja (viši OAHI) p=0,008, ali imaju manje centralnih apneja po satu spavanja (niži CAI) p=0,041, što pridonosi statistički neznačajno nižem ukupnom AHI-u (p=0,762) u djece s Downovim sindromom. Prosječno i najdulje trajanje apneja nije se značajno razlikovalo između dviju skupina. Djeca s Downovim sindromom su imala značajno niže i prosječne i nadir saturacije kisika (p=0,008 i p=0,001). Zaključak: Možemo prevenirati većinu respiratornih komplikacija u djece s Downovim sindromom podizanjem svjesnosti njihovih roditelja o poremećajima spavanja u te djece, ali i zdravstvenih djelatnika, te uključivanjem rutinske cjelonoćne videopolisomnografije u njihovo praćenje.

Aim: To compare the diagnostic values and limitations of quantitative fluorescent polymerase chain reaction (QF-PCR) and conventional cytogenetic analysis in prenatal diagnosis of chromosomal abnormalities. Methods: A prospective study included simultaneous QF-PCR and cytogenetic analysis of 133 prenatal samples routinely obtained by amniocentesis or chorionic villus sampling (CVS). Additionally, QF-PCR analysis was performed on 14 tissue samples collected after termination of pregnancy (TOP) for which karyotyping could not be performed due to culture failure. Results: Among 133 analyzed prenatal samples, chromosomal abnormalities were diagnosed in 12 cases (9%), including 10 cases of numerical chromosomal aberrations and two cases with unbalanced structural rearrangements. Nine out of 12 chromosomal abnormalities were also detected with QF-PCR. However, all cases of major aneuploidies were successfully disclosed with QF-PCR, resulting in 100% detection rate for chromosomes 21, 18, 13, X and Y. Using a set of markers specific for chromosomes 21, 18 and 13, QF-PCR analysis of tissues collected after TOP revealed chromosomopathy in 21.4% of cases (two cases of trisomy 18 and one triploidy). A comparison of STR markers confirmed monozygosity in two monochorionic/diamniotic twin pregnancies. Conclusion: QF-PCR has been shown as a rapid and reliable method for prenatal diagnosis of the most common chromosomal aneuploidies, and as an adequate alternative to conventional karyotyping in cases where cytogenetic analysis is not possible due to failure of culturing process. However, conventional cytogenetics still presents a gold standard for the detection of structural aberrations and rare aneuploidies.

Objective The objective was to compare the results of a complete chromosomal, genetic and histological investigation in 13 azoospermic men with the results of the intracytoplasmic sperm injection (ICSI) procedure. Study design Peripheral blood samples were used for the measurement of follicle-stimulating hormone (FSH) levels, chromosomal analysis, microdeletions in the azoospermia factor (AZF) region of the Y chromosome and cystic fibrosis transmembrane conductance regulator (CFTR) mutation analysis. Testicular tissue was used for histological scoring and cytogenetic evaluation. Results Peripheral blood cytogenetic analysis revealed a normal male karyotype in all cases. Chromosomal analysis from testicular tissue revealed a mosaicism for the terminal deletion of chromosome 22 with a breakpoint site at 22q13 in one patient with congenital bilateral absence of the vas deferens (CBAVD). Deletions in the AZFa, ATFb, and AZFc regions were not detected. The CFTR mutational analysis showed normal results in all patients. Conclusions Cytogenetic evaluation of testicular tissue should be performed in non-obstructive and obstructive azoospermic patients as well as in patients with multiple failed IVF and recurrent spontaneous abortion.

Clinical features in patients with segmental aneuploidy often vary depending on the size of the chromosomal region involved. Monosomy 2p is usually observed as a part of more complex syndromes among proband of balanced reciprocal translocation carriers. Partial monosomy 2p (2p25.1→pter) has also been shown to cause a characteristic phenotype associated with severe mental retardation. Trisomy of the long arm of chromosome 4 is well studied pathology. Patients with dup4q syndrome have variable clinical features, which are both related to the size of duplicated segment of the chromosomal arm 4q and specific associated monosomy. Clinical findings were compatible with those previously reported in dup4q and del2p patients. Although partial trisomy 4q and partial monosomy 2p vary in their phenotypes, they also have many features in common such as developmental delay, mental retardation, hypertelorism, low set ears, epicanthic folds and hand anomalies. Herein are presented the clinical and cytogenetic findings in a 4-years-old female with karyotype 46, XX, der(2)t(2 ; 4)(p25.1 ; q31.3)pat. Clinical phenotypes in these translocation cases are variable, because the involved breakpoints vary case-by-case. We compare in this report similarity of the clinical features of our patient and other patients carrying a duplication of the distal part of 4q and patients carrying a deletion of distal part of 2p as described in the literature. To our knowledge, this is the first case of partial trisomy 4q accompanied with partial monosomy for 2p.

Phenotypes in patients with segmental aneuploidy often vary in their clinical manifestation depending on the size of the chromosomal region involved. Recently defined microdeletion syndrome 8p23.1 is characterized by congenital heart disease, developmental delay and a characteristic behavior profile with hyperactivity and impulsiveness. On the other hand, more than 75 cases of trisomy 4p have been reported thus far, most of them due to unbalanced translocations. Trisomy 4p has been shown to cause a characteristic phenotype associated with characteristic facial appearance, postnatal growth retardation, severe psychomotor retardation with or without seizures, microcephaly and various major and minor anomalies. The large variability of the phenotype in trisomy 4p syndrome may be explained by the variation in length of the duplicated segments. Here we present clinical and cytogenetic findings in a 5-month old boy with a duplication of a chromosomal segment 4p16.1→4pter and a deletion of a chromosomal segment 8p23.1→8pter. His karyotype is determined by applying classical GTG banding and FISH probes (WHSCR region, cen 4, cen 8, tel 8p): 46, XY, der(8)t(4 ; 8) (4pter→4p16.1::8p23.1→8qter)dn. Patient’s parents are not related and have normal karyotypes. We have compared similarity of the clinical features of our patient to other patients carrying a duplication of the distal part of 4p and patients carrying a deletion of distal part of 8p as described in the literature. To the best of our knowledge, until today there has been only one report of a combination of dup4p and del8p syndrome. Compared to mentioned case, our patient has less severe manifestations, probably due to a more distal 4p trisomy.

Although, deletion of short arm of chromosome 18 is one of the most frequent autosomal terminal deletions, mosaic form of 18p deletion is infrequently observed. Furthermore, prenatally detected cases of 18p deletion and isochromosome 18q mosaicism are extremely rare. Herein, we present a case of del(18p)/i(18q) mosaicism, prenatally detected after chorionic villus sampling. A 37-year-old woman was referred for prenatal diagnosis because of fetal septated cystic hygroma measuring 4.3 mm. Cytogenetic analysis showed a mosaic 46, XX, del(18)(p11.2)/46, XX, i(18)(q10) karyotype in both, short- and long-term culture. Parents elected to terminate the pregnancy. Fetal mosaic karyotype was confirmed by chromosomal analysis of cultured skin fibroblasts. Molecular characterization of chromosome 18 structural aberrations was performed by fluorescence in situ hybridization (FISH). Considering variable ultrasound findings among cases with del(18p)/i(18q) mosaicism, we emphasized that first and second trimester ultrasound screening examinations for fetal malformations, followed by cytogenetic and molecular evaluations, are very important in the management of prenatally detected cases.

Objective: Analysis of prenatally diagnosed sex chromosome aneuploidies and disorders of sex development (DSDs). Methods: This study includes a retrospective data analysis of 46 prenatally detected sex chromosome aneuploidies and one case of 46,XY DSD diagnosed during an 11-year period (2002–2012) at our department. Results: Of the 46 sex chromosome aneuploidies, 29 cases (63.0%) were in the group of a selected population of women according to abnormal first-/second-trimester ultrasound and 17 (37.0%) cases in an unselected population of women who underwent fetal karyotyping because of advanced maternal age. The most common aneuploidy was Turner syndrome in full and mosaic form (50%). Complete androgen insensitivity syndrome was diagnosed in the case of 46,XY DSD. Conclusions: Sex chromosome aneuploidies must be taken into consideration if, in the first or second trimester, abnormalities are revealed on ultrasound, mainly Turner syndrome in full or mosaic form and 47,XYY.

Prenatally detected cases of 13q-syndrome are infrequently reported, especially those with proximal deletion 13q. To the best of our knowledge, case 2 presented by Tosca et al. (2011) in the article discussing genotype–phenotype correlation in patients with interstitial deletion 13q13.3 to 13q21.3, and the report of Miyake et al. (2008) on del(13)(q21.1q22.3) found in the fetus with a duodenal atresia are the only two reports on the prenatally diagnosed cases with interstitial deletion of 13q proximal segments. Herein, we present a case of del(13)(q12.3q22) in a fetus with a septated cystic hygroma, prenatally ascertained after chorionic villus sampling.

The aim of the study is to investigate the efficiency of the second-trimester biochemical screening, with maternal serum alpha-fetoprotein (MS-AFP) and free beta-subunit of human chorionic gonadotropin (free beta-hCG), during the ten-year period. The study included 11,292 of pregnant women between the 15th and 18th gestational week, who underwent screening from November 1996 to December 2006. The risk for trisomy 21 and trisomy 18 were calculated by computer software, based on a model which generated the final risk for fetal aneuploidies from the pregnant woman's a priori age risk and the likelihood ratio of the distribution of the biochemical markers, according to the second-trimester gestation. With the cut-off value of the final riskor = 1:250, the detection rate for trisomy 21 was 75% (21/28). In women less than or equal to 35, the detection was 57.1% (8/14) and 92.9% (13/14) in those over 35 years, respectively. The detection rate of trisomy 18 was 50% (2/4). The results confirmed that the implementation of double-test, as non-invasive screening for fetal aneuploidies, should be accepted as a complementary method of antenatal care.

Hypophosphatasia is a metabolic bone disease characterized by bone and teeth hypomineralization due to defective function of tissue-nonspecific alkaline phosphatase (TNSALP). The disorder is caused by various mutations in the TNSALP gene localized on short arm of chromosome 1. Infantile hypophosphatasia is a severe form of the disease inherited as an autosomal recessive trait which presents before age of six months and often has fatal outcome. We report a patient with typical clinical course for infantile hypophosphatasia who was homozygous for the c.1402G>A mutation. The same mutation has been previously associated with a more severe perinatal form also in a Croatian family what indicates a possible common ancestral origin and phenotypic variability potential of c.1402G>A mutation of TNSALP gene.

Modern management of Rh alloimmunization includes early diagnosis of fetal RhD genotype, precise assessment of the severity of fetal anemia and the use of minimal number of invasive diagnostic and therapeutic procedures. The severity of fetal anemia can be assessed by Doppler ultrasound, while fetal RhD genotype is determined from the amniotic cells or fetal DNA extracted from the mother's serum by polymerase chain reaction (PCR). Although prenatal RhD genotype diagnostic techniques have been used in developed countries more than 10 years, they have not been available in Croatia until recently. As a consequence of unavailability of these techniques in Croatia there has been inadequate approach to the patient, in whom inappropriate and unnecessary visits, amniocentesis, cordocentesis and laboratory tests were performed. Therefore, we describe the first case of successful prenatal diagnosis of fetal RhD genotype by PCR analysis of DNA extracted from amniotic fluid cells.

Sindrom potpune neosjetljivosti na anđrogene otkriva se u djevojčica adolescentne dobi s izostankom menarhe ili djevojčica mlađe dobi s ingvinalnom hernijom. Ginekološki nalaz otkriva izostanak razvoja struktura koje nastaju od Miillerovih kanala (maternice, jajovoda i gornjega dijela vagine). Fenotipski to su djevojčice, ali s muškim spolnim komplementom (46,XY). Klasični se kariogram nadopunjuje probom FISFI SRY. Gen SRY kod tih je djevojčica posve normalne funkcije te one imaju normalno razvijene testise koji su smješteni intraabdominalno ili ingvinalno. Sindrom je posljedica mutacije gena za receptor androgena koja se nasljeđuje X-vezano recesivno i potvrđuje molekulamo-genetičkom analizom. Iako se radi o potpuno zdravim osobama, njihova dijagnoza ima psihosocijalne posljedice koje zahtijevaju multidisciplinami pristup., Complete Androgen Insensitivity Syndrome is found in adolescent girls with the absence of menarche or in younger girls with inguinal hernia. The absence of structures that develop from Müllerian ducts (uterus, oviducts and upper part of vagina) was found during gynecological examination. Phenotypically they are female, but with a male genotype (46, XY). Classical karyogram is supplemented with FISH SRY probe. SRY gene functions normally in these girls, so that they have normal male gonads situated intraabdominally or inguinally. Syndrome is caused by the mutation of androgen receptor that is inherited X-linked recessively and confirmed by molecular genetic analysis. Although they are completely healthy persons, their diagnosis has psychosocial consequences that require a multi-disciplinary approach.

SAŽETAK Posljednjih godina došlo je do naglog razvoja dijagnostičkih metoda kojima se može otkriti genetski uzrok neplodnosti, a time procijeniti i rizik prijenosa genetskog poremećaja. Razvojem tehnika potpomognute oplodnje moguće je liječiti veoma teške oblike neplodnosti koji nose značajno veći rizik prijenosa određenih molekularnih promjena na potomstvo. Kod takvih slučajeva veoma je važno otkriti mutacijsku promjenu, jer se time pruža mogućnost davanja precizne genetske informacije o rizicima nasljeđivanja i načina prenatalnog određivanja genotipa ploda. S obzirom na to da ne postoje jedinstvene smjernice u pristupu dijagnostike i liječenja neplodnosti, nastoje se izdvojiti skupine visokorizičnih neplodnih bolesnika prema njihovim kliničkim osobitostima koje će biti podvrgnute rutinskim dijagnostičkim postupcima u svrhu otkrivanja uzroka neplodnosti. Za određene genske poremećaje, kao što su cistična fibroza i sindrom fragilnog X, poznata je uloga u etiopatogenezi neplodnosti. Najnovija molekularna istraživanja genskih mutacija, posebice u β-podjedinici FSH i LH gena, pokazuju svoju dijagnostičku i kliničku vrijednost kod otkrivanja genetskih uzroka neplodnosti., During the last few years, there is a rapidly expansion of new diagnostic techniques improving the detection of genetic causes of infertility. It is followed by a precise risk assessment of genetic change transmission and possibility to chose the most adequate methode of medically assisted reproduction. The treatment of severe forms of both male and female infertility became possible by the development of very sofisticated in vitro fertilising techniques. Such patients carry the significantly higher risk of having mutational change in one of the disease genes involved in regulation of human reproduction. The detection of mutation in these patients improve the treatment and prognostic assessment in potential future pregnancies. The unique guidelines for the diagnosis and the treatment of infertile couples still doesn’t exist. There are several categories of patients selected by clinical features and associated with some forms of genetic abnormalities. For particular genetic disorders such as cystic fibrosis and fragile X syndrome, their role in pathogenesis of infertility is very well known. Every day, new genetic mutations associated with infertility are discovered. The recent studies involving investigations of significance of molecular mutations, particulary in the gene for the β-subunit of FSH and LH , showed thier diagnostic and clinical value in evaluation both male and female infertility.

Adequate periconceptional folic acid (FA) intake reduces the risk of neural tube defects. There are still no official FA supplementation guidelines, FA fortification policies or larger studies of awareness regarding FA or number of planned pregnancies in Croatia. This study assesses the knowledge and practice regarding FA supplementation and reports the trends in pregnancy planning in Croatia. A total of 569 pregnant women completed an anonymous questionnaire and about 72% of them were aware of the benefits of FA. Despite 75.53% of planned pregnancies, only 14.41% of all women took FA appropriately. Croatian women get information about FA from the media, health professionals and friends, but 63.77% got this information too late. The present study showed low percentage of appropriate FA intake despite high number of planned pregnancies in Croatia. It emphasizes the need for immediate and continuous public health education initiative about FA intake targeted to the women of childbearing age before their pregnancies have occurred.

The empty follicle syndrome (EFS) is defined as a lack of retrieved oocytes from follicles, at the time of repeated aspiration and flushing, following ovulation induction. The actual mechanism responsible for the EFS is still unknown. The aim of this study was to offer more information regarding the possible connection of this syndrome with pericentric inversion of chromosome 2. We give a case report of a patient who had multiple failed IVF attempts, due to the absence of oocyte and granulosa cells in the follicular fluid, following oocyte retrieval in both stimulated and natural cycles. Chromosomal analysis showed the presence of a pericentric inversion of chromosome 2: 46, XX, inv(2)(p11q21) in the female partner karyotype, while the male partner had a normal karyotype. Our case showed possible genetic factor influence in the aetiology of EFS.

Testicular juvenile granulosa cell tumor (TJGCT) occurs predominantly in infancy and may be associated with sex chromosomal abnormalities. We report a fetus aborted because of cytogenetically confirmed complete XXY triploidy. External genitalia of the fetus were female, with a short and patent vagina. The tumor presented as an abdominal multicystic mass with typical histologic and immunohistological features of JGCT. It was connected with a tubular uterus-like structure. The other gonad was an inguinally localized testis that showed histologically a Sertoli cell adenoma. Malformations typical for triploidy were also present: agenesis of the corpus callosum, stenosis of the pulmonary ostium, and hypoplasia of the lungs and adrenals. To our knowledge this is the first case of TJGCT in a triploid fetus.

Interferons (IFNs) are a group of cytokines exhibiting antiviral, antiproliferative and immunoregulatory properties. The principal stimulus for the synthesis of IFNs is the presence of viral double-stranded RNA, although rare examples of constitutive synthesis have also been described. The aim of the present study was to determine IFN-alpha-like biological activity in the seminal plasma, follicular and amniotic fluid, embryo culture medium, and fetal blood obtained from patients without apparent viral or bacterial infections. Interferon-alpha-like biological activity was determined by a standard cytopathic effect inhibition bioassay. The study included two groups of patients. The first group consisted of 30 married couples participating in the programme for assisted reproduction and the second group consisted of 23 patients scheduled for prenatal diagnosis (15 for amniocentesis and eight for cordocentesis). The seminal plasma of infertile men (asthenozoospermia, oligoasthenozoospermia) contained a high titre of IFN-alpha-like antiviral activity. Asthenozoospermia was diagnosed in men with a normal sperm concentration but less than 50% progressively motile sperm and oligoasthenozoospermia was diagnosed in men with a sperm count less than 1 x 10(6) mL(-1). Despite slightly higher antiviral titres in the seminal plasma obtained from asthenozoospermic patients, no clear association between IFN-alpha-like biological activity and sperm concentration was found. Interferon-alpha-like biological activity was found in all samples of follicular and amniotic fluid and in fetal blood of patients with intrauterine growth retardation and trisomy 18. Antiviral titres from seminal plasma and follicular fluids were significantly higher compared with amniotic fluids and fetal blood. Embryo culture medium did not contain IFN-alpha-like biological activity. Our results demonstrate that IFN-alpha-like activity in biological fluids is relevant for reproduction, even in the absence of infection.

Objective. To estimate the degree of risk of the echogenic intracardiac foci (IEF) for fetal chromosomopathies and to determine its association with structural anomalies of the fetus. Material and methods. During the period of two years 190 pregnant patients had been send for fetal echocardiography. Examination had been performed by transvaginal¬ (12–17 weeks of gestation) or transabdominal approach (18 weeks or more of gestation). Results. IEF was observed in 17 fetuses, multifocal appearance was found in 2 out of 17 fetuses. In 3 cases IEF had resolved during the 8 weeks period of time. Additional structural anomalies were detected in 11 fetuses. In 2 fetuses trisomy 21 had been confirmed. Conclusion. A single soft marker as IEF is commonly encountered during the second trimester among the fetuses with chromosomal aberation. As do many sonographic markers IEF can be resolved during the pregnancy and often can be found in normal fetuses., Cilj rada je bio na vlastitom uzorku utvrditi u kojoj mjeri ultrazvučni nalaz hiperehogenih intrakardijalnih žarišta (IEF) pridonosi dijagnostici kromosomopatija i strukturalnih anomalija. Uzorak i metode. Tijekom dvije godine 190 trudnica između 12. i 39. tjedna trudnoće je primljeno radi fetalne ehokardiografije. Pregled je obavljen vaginalnom sondom od 5 MHz pri trudnoćama 12.–17. tjedna ili zavinutom abdominalnom sondom od 3,5 MHz nakon 17. tjedna trudnoće. Rezultati. IEF su nađeni u 17 fetusa, multifokalni u 2 od njih. U 3 fetusa su IEF u roku od osam tjedana nestali. U 11 fetusa su nađene dodatne strukturalne anomalije. Trisomija 21 je potvrđena u 2 fetusa. Zaključak. IEF su »meki« ultrazvučni biljezi fetalne aneuploidije, često su prolazni, a nalaze se i u eukariotičnih fetusa.

We present a case of 26-year-old woman with posttraumatic chronic osteomyelitis caused by Vibrio alginolyticus, contracted after contamination of a tibial fracture with seawater. The patient underwent bone resection and bifocal osteosynthesis according to Ilizarov and was treated with a combination of ciprofloxacin and tetracycline. The patient responded in the same way to distraction osteogenesis as any other patient with chronic osteomyelitis with large defects.

Objective: Our purpose was to determine if the frequency of confined placental mosaicism in newborns with unexplained intrauterine growth retardation (IUGR) was higher compared with infants with appropriate growth in utero and the outcome of these pregnancies. Study Design: A total of 20 cases with unexplained IUGR and 20 cases with appropriate growth for gestational age has been studied. Amnion, chorion and villi biopsy specimens were obtained from growth-retarded cases and controls at delivery. Cord blood specimens for 48-hour lymphocyte cultures were obtained from all infants with IUGR. Results: Karyotype analysis revealed confined placental mosaicism in two of 20 (10%) cases with IUGR. In one growth retarded case and one appropriate growth for gestational age case, mosaicism was also confirmed in the amnion. Cytogenetic analysis from peripheral blood of newborns showed normal karyotype in all cases. Three pregnancies in the group of fetuses with IUGR (15%) ended with fetal death compared with normal fetal surveillance of all cases from the control group. Conclusion: Confined placental mosaicism was detected two times more frequently from placentas of growth- retarded infants compared with those of newborns with appropriate growth. The fetal loss was significantly higher in the group of cases with IUGR compared with the control group.

OBJECTIVE: The aim of this brief investigation was to correlate the most common sonographically detectable markers with certain type of chromosomal disorder diagnosed by available karyotyping procedures. STUDY DESIGN: During the 3 year study period fetal karyotyping was performed in 1055 patients for a variety of clinical indication. Twenty one percent (21% ; 222/1055) of procedures were done because of sonographically detectable structural disorders related to phenotype expression of chromosomopathies. Sonographic examinations and karyotyping procedures were performed between the 10th and 36th week. The average maternal age was 27 years, unselected. RESULTS: The fetal karyotype was abnormal in 13.5% of cases (30/222). Within the group of single marker, 11.6% (7/60) of karyotypes were abnormal. Multiple markers of chromosomal abnormalities resulted in 14.2% (23/162) of abnormal karyotypes. The most frequent chromosomal disorder detected in sonographic screening is trisomy 18 (50% ; 15/30). The data on the frequency of different types of chromosomal abnormalities are given. CONCLUSIONS: The incidence of chromosomal abnormalities for ultrasonographically detectable malformations is much higher than the incidence reported in screening studies based on maternal age or biochemical screening. Trisomy 21 showed the relative lack of variety in phenotypic expression, and nuchal translucency screening has to be accepted rationally. Associated numerous major and minor malformations were the most prominent factors leading to the diagnosis of chromosomopathies, particularly trisomy 18.