Ana Vičić

Trisomy 1 in an early pregnancy failure

About half of all human conceptions abort spontaneously even before clinical recognition of the pregnancy [Boklage, 1990]. Furthermore, approximately 10–15% of clinically recognized pregnancies end in spontaneous abortion, mostly before the end of the first trimester [NyboAndersen et al., 2000]. Fifty to 70% of these early miscarriages are caused by chromosome abnormalities with the most common abnormality observed being trisomy, accounting for about 60% of all abnormal karyotypes [Philip and Kalousek, 2002]. To date, trisomies of all chromosomes have been observed, and the most rare trisomy is trisomy 1 [Hassold and Jacobs, 1984; Banzai et al., 2004]. Although, cytogenetic analysis of preimplantation embryos, donated from patients undergoing in vitro fertilization (IVF), showed that trisomy 1 does occur [Bahçe et al., 1999], so far only three cases with a full trisomy 1 in a clinically recognized pregnancy have been reported. In these three cases pregnancies were terminated before 9th week of gestation with a blighted ovum [Hanna et al., 1997; Dunn et al., 2001; Banzai et al., 2004]. Herein we present the fourth report of a full trisomy 1 in an early pregnancy failure. This 27-year-old G3PO female was referred for sonographic examination which demonstrated the presence of gestational sac and yolk sac, but the absence of embryonic pole development and fetal heart beat. The diagnosis was blighted ovum and dilatation and curettage (D&C) was performed at 51 days post-last menstrual period (LMP). Products of conception were sent to our laboratory for cytogenetic analysis. Chorionic villi, isolated from products of conception, were cultured and cytogenetic analysis by G-banding showed a 47,XX, þ1,inv(9)(p11q13) karyotype (Fig. 1). Her family history was negative, except for two previous spontaneous abortions. The first, at the age of 25, and the second, at the age of 26, terminated at 9 and 7 weeks of gestation, respectively. Since the couple had infertility, cytogenetic analysis of their blood samples was performed. The father’s karyotype was normal, 46,XY, and the mother’s was 46,XX,inv(9)(p11q13), showing that the variant pericentric inversion of chromosome 9, present in conceptus, was of maternal origin. Autosomal trisomies are found in more than half chromosomally abnormal spontaneous abortions. The most commonly seen is trisomy 16 which accounts for approximately 30% of all trisomies found in miscarriages [Hassold and Jacobs, 1984]. In contrast, trisomy 1 is the rarest, since it has been identified, in only four cases, including our report [Hanna et al., 1997; Dunn et al., 2001; Banzai et al., 2004]. The origin of autosomal trisomies is, in most cases, nondisjunction during maternal meiosis. Although, theoretically all chromosomes should have equal frequency of nondisjunction, Hassold and Jacobs [1984] suggest that the rate of nondisjunction varies among chromosomes and that chromosome 16 has the highest rate among autosomes. Furthermore, chromosomal analysis of human oocytes showed that chromosomes of some groups (A and C) have lower frequency of nondisjunction than expected [Pellestor et al., 2005]. Thus, lower rate of nondisjunction of chromosome 1 could be one of the reasons why trisomy 1 is so infrequent. Although, rarely found in spontaneous abortions, cytogenetic analysis of embryos from patients undergoing IVF showed that trisomy 1 occurs in greater rate in preimplanted embryos [Bahçe et al., 1999]. However, analysis of embryo development showed that chromosomally abnormal embryos, especially those with monosomies and rare trisomies, are

Prenatal diagnosis of sex chromosome aneuploidies and disorders of sex development – a retrospective analysis of 11-year data

Abstract 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.

Prenatal diagnosis of Down syndrome: A 13-year retrospective study

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.

Prednosti i ograničenja invazivne prenatalne dijagnostike

Prenatalna dijagnostika kromosomskih poremećaja podrazumijeva citogenetičku analizu stanica ploda dobivenih jednom od rutinskih invazivnih tehnika biopsijom korionskih resica, placentocentezom, amniocentezom ili kordocentezeom. Izbor tipa invazivne dijagnostike ovisi ponajprije o individualnoj procjeni čimbenika rizika za rađanje kromosomski bolesnog djeteta, a zatim i o riziku lošeg ishoda, odnosno gubitka trudnoće kao najteže komplikacije invazivnog zahvata. Problemi koji se mogu javiti u prenatalnoj dijagnostici kromosomskih poremećaja su pojava kromosomskog mozaicizma te razlikovanje pravog od pseudomozaicizma, rizik neuočavanja suptilnih kromosomskih razmještanja zbog ograničenja razlučivanja svjetlosnog mikroskopa, nemogućnost detekcije kriptičkih mozaičnih oblika te zagađenje majčinim stanicama. U tim se slučajevima uz klasičnu citogenetičku analizu provodi i neka od metoda molekularne dijagnostike. Poseban izazov u prenatalnoj dijagnostici su blizanačke trudnoće. Uvođenjem metoda potpomognute oplodnje i novih protokola stimulacije, značajno se povećao broj višeplodnih trudnoća. Razlikovanje monozigotnih od dizigotnih blizanaca kod dikorijalnih diamnijskih blizanaca istog spola može se precizno odrediti usporednom analizom mikrosatelitnih lokusa. Mehanizmima kao što je postzigotno nerazdvajanje može doći do nastajanja različitih kromosomskih statusa, čak i kod monozigotnih blizanaca. Zato je amniocenteza tehnika izbora, a uzorci se trebaju uzeti iz svake amnijske vreće, posebice ako jedan ili oba blizanca imaju ultrazvučno dijagnosticirane abnormalnosti.

Prenatally detected interstitial deletion 13q12.3–q22 in a fetus with a cystic hygroma

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.