Molecular cytogenetic characterization of 1q42.3q44 deletion and 8q24.3 duplication in a fetus with single umbilical artery and ventricular septal defects.

OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic characterization of a chromosome 1q42.3q44 deletion and 8q24.3 duplication in a fetus with single umbilical artery and ventricular septal defects, and we discuss the genotype-phenotype correlation. CASE REPORT: Here, we describe a fetus with abnormal sonography findings showing a single umbilical artery and ventricular septal defects. Conventional karyotyping initially described the fetus as 46,XX,1q? and molecular cytogenetic analysis (CMA) revealed a 13-Mb deletion and 4.6-Mb duplication of regions 1q42.3q44 and 8q24.3, respectively. The father's karyotype was 46,XY. The mother's karyotype was 46,XX,t(1;8)(q42;q24). Therefore, the karyotype of the fetus was identified as 46,XX,der(1)t(1;8)(q42;q24) mat. After genetic counseling, the couple chose to terminate the pregnancy. We suggest that the ACTN2, RYR2 and PUF60 genes may be responsible for the ultrasound abnormalities observed in the fetus. CONCLUSION: To the best of our knowledge, this is the first report of a 1q deletion and 8q duplication identified by prenatal detection. The application of karyotype analysis and CMA provides more accurate characterization for unidentified chromosomal anomalies, and benefits appropriate genetic counseling in the clinic.

Prenatal diagnosis of familial 2p15 microduplication associated with pulmonary artery stenosis, single umbilical artery and left foot postaxial polydactyly on fetal ultrasound.

OBJECTIVE: We present prenatal diagnosis of familial 2p15 microduplication associated with pulmonary artery stenosis, single umbilical artery and left foot postaxial polydactyly on fetal ultrasound. CASE REPORT: A 34-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed the karyotype of 46,XX. Prenatal ultrasound examination at 21 weeks of gestation showed pulmonary artery stenosis, single umbilical artery and left foot postaxial polydactyly. Repeat amniocentesis was performed at 22 weeks of gestation and array comparative genomic hybridization (aCGH) analysis on the DNAs extracted from amniocytes revealed the result of arr 2p15 (61, 495, 220-62,885,679) × 3.0 [GRCh37 (hg19)] with a 1.391-Mb 2p15 duplication encompassing seven Online Mendelian Inheritance in Man (OMIM) genes of USP34, XPO1, FAM161A, CCT4, COMMD1, B3GNT2 and TMEM17. aCGH analysis on the DNAs extracted from parental bloods confirmed a familial transmission from a normal carrier mother who had no phenotypic abnormality. A 3270-g female baby was delivered at term with mild pulmonary artery stenosis and left foot postaxial polydactyly. The infant had normal physical and psychomotor development when follow-up at age of one year. CONCLUSION: Prenatal diagnosis of fetal structural abnormalities should include aCGH analysis in addition to conventional cytogenetic analysis.

Pulmonary Infantile Hemangioma Mimicking a Congenital Cystic Adenomatoid Malformation.

Infantile hemangioma (IH) is the most common benign vascular tumor of infancy, occurring predominantly in the head and neck. It is characterized by specific endothelial expression of glucose transporter-1 (GLUT-1) and involution with time, spontaneous or on beta-blockers treatment. Although some predisposing factors are known, the exact pathogenesis remains unclear. We report a case of pulmonary IH GLUT-1 positive, initially suspected as a cystic pulmonary airway malformation, in a child presenting with both cardiac and renal malformations. The clinical, radiological, pathological, and genetics findings are discussed with a review of the literature. Although pulmonary IH is a rare lesion, it should be suspected when facing a pulmonary cystic mass in a child.

Single umbilical artery and reproduction losses in Slovak population: relation to karyotype and fetal anomalies.

AIM: The purpose of this study was to monitor the association between single umbilical artery (SUA), chromosomal abnormalities and associated anomalies during the routine examination of spontaneous or induced miscarriages and premature births. METHODS: During 1992-2015 we morphologically and cytogenetically examined a series of 4098 samples. For 1330 cases the number of umbilical cord vessels could be reported. RESULTS: The presence of single umbilical artery was identified in 67 fetuses of 1330 pregnancies (5.04 %); 36 of the 67 fetuses (53.7 %) had additional congenital malformations. The cultures were unsuccessful in 29 of 67 cases (43.3 %). 38 cases (56.7 %) were successfully karyotyped; 20 out of them had a normal karyotype and 18 had chromosomal anomalies including trisomy 18 (n = 4), trisomy 13 (n = 3), trisomy 21 (n = 2), trisomy 11 (n = 1), triploidy (n = 3), monosomy X (n = 3) and structural chromosomal aberrations (n = 2). CONCLUSION: Isolated SUA is not at increased risk of chromosomal abnormalities and generally does not endanger pregnancy. All chromosomally abnormal embryos and fetuses had associated congenital anomalies. The most frequently associated congenital anomalies were in the musculoskeletal system, central nervous system and genitourinary tract (Tab. 4, Ref. 44).

Demographic and perinatal outcome data of fetuses with SUA/PRUV.

AIM: Identify structural anomalies and adverse pregnancy outcomes accompanying single umbilical artery (SUA) and persistent right umbilical vein (PRUV) and to investigate whether SUA and PRUV are associated with chromosomal abnormalities and if these defects warrant invasive antenatal diagnosis. METHODS: We retrospectively analyzed pregnancies with an antenatal diagnosis of SUA/PRUV from the International Peace Maternity and Child Health Hospital (IPMCHH) database. Data of structural malformations, fetal karyotyping, and pregnancy outcomes were analyzed. RESULTS: Results revealed that 13.9 and 7% of SUA and PRUV cases, respectively, had malformations. Furthermore, 60% of the malformations accompanying SUA were isolated congenital heart disease (CHD), and 50% of the malformations accompanying PRUV were multiple malformations including CHD. All primarily diagnosed isolated PRUV (iPRUV) cases and 92.6% of primarily diagnosed iSUA cases had normal fetal echocardiography. Cases of iSUA and iPRUV with indications of invasive antenatal diagnosis showed no chromosomal abnormalities. The emergency cesarean section rate did not differ between the study population and the IPMCHH general population (p = .184). CONCLUSION: Patients of SUA and PRUV diagnosed in secondary hospitals should be referred to tertiary medical center for further ultrasonography. SUA and PRUV are not indicators for invasive antenatal diagnosis and selective cesarean section.

Embryonic hypocellularity, blastogenetic malformations, and fetal growth restriction.

An association between congenital malformations and fetal growth restriction (FGR) can be largely explained by a relationship with early embryonic hypocellularity. The malformations include the VACTERL association, which is exceptional as a Mendelian syndrome, but is commonly associated with monozygotic twinning, maternal diabetes, and some forms of aneuploidy, all characterized by a small embryo early in development. Parsimony suggests that these different links to VACTERL are related to the hypocellularity as a single common factor, rather than as an expression of three independent pathogenetic processes. A distinct non-genetic pathogenesis is further supported by increased frequencies in the same conditions of a single umbilical artery (SUA), which is also unusual in Mendelian disorders. SUA often involves the atrophy of one artery, which may be facilitated by altered hemodynamics in a smaller embryo, providing a direct link to hypocellularity. Hypocellularity may also explain a possible connection between VACTERL and certain mitochondrial disorders, where reduced energy might slow early cell division and growth, reducing the size of the embryo. © 2016 Wiley Periodicals, Inc.

The effects of isolated single umbilical artery on first and second trimester aneuploidy screening test parameters.

OBJECTIVE: Reliability of first and second trimester screening tests largely depends on accurate estimation of maternal serum marker values. Reduced reliability could lead redundant invasive tests or misdiagnosis. Adjustments of serum marker values for confounding factors like insulin-dependent diabetes, maternal weight or maternal rhesus status are essential. We aimed to investigate whether isolated single umbilical artery alters first and second trimester test parameters or not. METHODS: Routine detailed obstetric ultrasonographies performed were retrospectively screened for this study. Among spontaneously conceived singleton pregnancies, women who were found to have single umbilical artery without any additional structural anomalies or aneuploidies were selected. First and second trimester screening test results were accessible for 98 and 102 of the cases with isolated single umbilical artery, respectively. RESULTS: Among first trimester screening test parameters, PAPP-A (pregnancy-associated plasma protein A) MoMs were found significantly higher in isolated single umbilical artery group. AFP MoMs were found significantly elevated in isolated single umbilical artery group in second trimester quadruple tests. CONCLUSION: Existence of single umbilical artery could alter the estimation of MoM values of maternal serum markers. Reliability of prenatal screening tests could be improved by adjusting these parameters in accordance with isolated single umbilical artery.

De novo unbalanced translocation resulting in monosomy for distal 5p (5p14.1 → pter) and 14q (14q32.31 → qter) associated with fetal nuchal edema, microcephaly, intrauterine growth restriction, and single umbilical artery: prenatal diagnosis and molecular cytogenetic characterization.

OBJECTIVE: To present prenatal diagnosis of partial monosomy 5p (5p14.1 → pter) and partial monosomy 14q (14q32.31 → qter). MATERIALS AND METHODS: A 33-year-old woman underwent amniocentesis at 20 weeks of gestation because of abnormal fetal ultrasound. Amniocentesis revealed a dicentric chromosome of dic(5;14). Level II ultrasound at 23 weeks of gestation revealed a fetus with intrauterine growth restriction, microcephaly, nuchal edema, a single umbilical artery, and fetal biometry equivalent to 19 weeks. At 23 weeks of gestation, she requested repeated amniocentesis. Whole-genome array comparative genomic hybridization on uncultured amniocytes was performed. Quantitative fluorescent polymerase chain reaction analysis was performed on uncultured cord blood and parental blood. A fetus was delivered with microcephaly, low-set ears, hypertelorism, depressed nasal bridge, increased nuchal fold, and a single umbilical artery. RESULTS: The fetal karyotype was 45,XX,dic(5;14)(p14.1;q32.31)dn. Whole-genome array comparative genomic hybridization analysis on uncultured amniocytes detected arr 5p15.33p14.1 (36,238-28,798,509)×1 and arr 14q32.31q32.33 (101,508,967-107,349,540)×1. Quantitative fluorescent polymerase chain reaction assays showed that the aberrant dic(5;14) was from paternal origin. CONCLUSION: Concomitant occurrence of monosomy for distal 5p and distal 14q my present nuchal edema, microcephaly, IUGR, and single umbilical artery on prenatal ultrasound.

Chromosome 18q-syndrome and 1p terminal duplication in a patient with bilateral vesico-ureteral reflux: case report and literature revision.

BACKGROUND: Vesico-ureteral reflux (VUR) is a dynamic event in which a retrograde flow of urine is present into the upper tracts. VUR may occur isolated or in association with other congenital abnormalities or as part of syndromic entities. We present a patient with a bilateral primary VUR, syndromic disease caused by a large deletion of 18q (18q21.3-qter) and terminal duplication of 1p (1p36.32-p36.33). CASE REPORT: The patient was 8 years old female with a disease including moderate growth retardation, psychomotor retardation, facial dysmorphism, single umbilical artery, umbilical hernia, urachal remnant, bilateral congenital clubfeet and renal-urinary disease. Chromosomal analysis and Array-CGH revealed two heterozygous chromosomal rearrangements: 1p terminal duplication and de novo 18q terminal deletion. She referred to our clinic to evaluation of bilateral hydronephrosis and right renal cortex thinning. Voiding cystourethrography demonstrated bilateral grade IV VUR and dimercaptosuccinic acid renal scintigraphy confirmed right renal cortex thinning and showed a cortical uptake of 75% of the left kidney and 25% of the right kidney. The patient underwent ureterovesical reimplantation after failure of 3 endoscopic submeatal Deflux injections with VUR resolution. CONCLUSIONS: This is the first report involving a patient with 18q-syndrome and contemporary presence of 1p chromosomal terminal duplication. The coexistence of two chromosomal rearrangements complicates the clinical picture and creates a chimeric disorder (marked by characteristics of both chromosomal anomalies). Kidney problems, primarily VUR is reported in 15% of patients affected by 18-q syndrome and no cases is reported in the literature regarding a correlation between VUR and 1p36 chromosomal duplication.