Enlarged cisterna magna in the third trimester as a clue to fetal trisomy 18.

Six of 19 fetuses with trisomy 18 confirmed by late karyotyping in the third trimester were found to have an enlarged cisterna magna (10 mm or more). For trisomy 18 conceptuses, there is a significant excess of females in both fetuses and livebirths; however, we found this ratio to be reversed in the third-trimester trisomy 18 fetuses with an enlarged cisterna magna (5 males vs. 1 female), indicating males are more likely to have this associated defect. Each of the 6 cases was associated with other trisomy markers including intrauterine growth retardation and polyhydramnios. Since a significant proportion of pregnancies may escape early prenatal care and some potentially detectable fetal abnormalities may be missed on early ultrasound and/or by maternal serum screenings, prenatal detection of an enlarged cisterna magna associated with intrauterine growth retardation and/or polyhydramnios in late gestation should prompt complete genetic counseling, rapid karyotyping and a careful search for other congenital anomalies.

Sirenomelia with an uncommon osseous fusion associated with a neural tube defect.

A sireniform infant presented with an uncommon osseous fusion of the lower limbs characterised by a fused femur, a partially fused tibia and sympus dipus with rudimentary digits and metatarsals. Associated abnormalities included sacral agenesis, a deformed pelvis, anorectal atresia, renal agenesis, cystic renal dysplasia, agenesis of the uterus and urinary bladder, ambiguous external genitalia, a single umbilical artery, a lumbosacral neural tube defect, and ventriculomegaly secondary to a Chiari II malformation. The pathogenesis of concurrent sirenomelia and neural tube defect is discussed.

Prenatal diagnosis of de novo proximal interstitial deletion of 14q associated with cebocephaly.

We report on the prenatal diagnosis of a case of cebocephaly, alobar holoprosencephaly, and microcephaly associated with a de novo proximal interstitial deletion of the long arm of chromosome 14: del(14)(q13q21.1) or (q13q21.2). This is the third case of holoprosencephaly in association with a deletion in this region. The present report concerns the association between prenatal craniofacial development, a holoprosencephaly locus, and the chromosomal segment 14q13.

Prenatal diagnosis of partial trisomy 12 and partial trisomy 21 due to a 3:1 segregation of maternal reciprocal translocation t(12;21) (p13.3;q21).

We describe the prenatal diagnosis and fetal phenotype of partial trisomy 12 (p13.3-pter) and partial trisomy 21 (pter-q21) due to a 3:1 segregation with tertiary aneuploidy transmitted from a maternal reciprocal translocation 12;21. Genetic amniocentesis of a 39-year-old gravida 2, para 1 woman at 19 weeks' gestation due to advanced maternal age revealed an unusual karyotype of 47,XY,+der(21)t(12;21)(p13.3;q21)mat. The pregnancy was terminated at 24 gestational weeks. The proband postnatally displayed by dysmorphic features of a round flat face with prominent cheeks and high forehead, upward slanting palpebral fissures, epicanthic folds, hypertelorism, a short nose, a broad and depressed nasal bridge, anteverted nares, a deformed philtrum, an open mouth, thin upper vermilion and broad everted lower lip, low-set ears with prominent anthelix and deep concha, broad hands with simian creases, a short neck, and cryptorchidism. The association of the involved chromosomal segments with the phenotype of Down's syndrome and trisomy 12p syndrome is discussed.

Prenatal diagnosis of a deletion of 18q in a fetus associated with multiple-marker screen positive results.

We report here the observations of positive maternal serum screening tests for Down syndrome, cytogenetic and molecular analysis, and dysmorphic fetal features in a pregnancy with 18q-syndrome. A 33-year-old primigravida was referred for genetic counselling because of multiple-marker screen positive results. At 14 weeks' gestation, the woman had a Down syndrome risk of 1:107 calculated from a maternal serum alpha-fetoprotein (MSAFP) level of 1.49 multiples of the median (MOM), a total human chorionic gonadotrophin (hCG) level of 2.42 MOM, and a serum unconjugated oestriol (uE3) level of 0.55 MOM. At 17 weeks' gestation, a repeat test showed a Down syndrome risk of 1:10 calculated from an MSAFP level of 1.09 MOM and a free beta-hCG level of 12.3 MOM. Genetic amniocentesis revealed a de novo deletion of 18q22.2-qter. Intrauterine fetal death occurred at 21 weeks' gestation. At birth, the fetus manifested clinical findings of the 18q-syndrome. The phenotype was correlated with the extent of the deletion. Linkage analysis of the family confirmed the extent and paternal origin of the deletion.

Perinatal features of omphalocele-exstrophy-imperforate anus-spinal defects (OEIS complex) associated with large meningomyeloceles and severe limb defects.

Omphalocele-Exstrophy-Imperforate anus-Spinal defects (OEIS complex), a combination of omphalocele, exstrophy of the bladder, an imperforate anus and spinal defects, arises from a single localized defect in the early development of the mesoderm that will later contribute to infraumbilical mesenchyme, cloacal septum, and caudal vertebrae. In this report, we document the perinatal features of two cases of OEIS complex associated with meningomyeloceles and severe lower limb defects, and discuss the prenatal diagnosis, inheritance, and differential diagnosis of this association of malformations. Although long-term survival can be achieved by successful corrective surgery, the associated structural defects such as large meningomyelocele and severe limb aplasia or hypoplasia, as seen in our patient, can influence the patient's quality of life. We would like to emphasize that an accurate prenatal diagnosis of OEIS complex and associated malformations is important for the detailed counseling of the family as well as appropriate perinatal management by the obstetricians, pediatric surgeons, urologists, neurosurgeons, and neonatologists.

Prenatal diagnosis of cephalothoracopagus janiceps monosymmetros.

We report a case of cephalothoracopagus janiceps monosymmetros that was diagnosed prenatally by ultrasound at 23 weeks' gestation. Obstetric ultrasound demonstrated conjoined female twins with a single fused cranial vault irregular in contour, duplicated cerebra, one face, two eyeballs, a fused thorax, two hearts, two thoracic spines, eight limbs, and polyhydramnios. The pregnancy was terminated and all the features described prenatally were observed at necropsy. The asymmetrical fused faces consisted of a ventral humanoid face with micrognathia, microphthalmia, low-set ears, a normal nose, and an opposite reduced face with partial facial features of a central narrowed fissure and paired synotic ears. The conjoined twins had fused umbilical cords, omphalocoele, and a single oesophagus, stomach, and duodenum, but duplicated pancreases, spleens, and central nervous, cardiopulmonary, hepatic, and genito-urinary systems. The common gastrointestinal tract bifurcated at the level of the jejunum. Our case documents a very uncommon variety of asymmetrical cephalothoracopagus janiceps with duplicated central nervous systems.

Skeletal deformities of acardius anceps: the gross and imaging features.

A morphology based imaging review is presented of the characteristic skeletal deformities associated with acardius anceps in three acardiac twins. These fetuses demonstrated poorly developed skulls, limb reduction defects, and phocomelia of the upper limbs, as well as narrow thoracic cages with or without the complete development of ribs, clavicles, scapulae, and cervical, thoracic, or lumbar vertebrae. However, their lower limbs and pelvic girdles were almost normal. The authors conclude that skeletal development is likely to be jeopardized in the area adjacent to the heart and in the cephalic portion of the body in fetuses with acardius anceps, and suggest vascular deficiency and hypoperfusion as pathogenetic mechanisms in this type of skeletal deformity.

Cebocephaly, alobar holoprosencephaly, spina bifida, and sirenomelia in a stillbirth.

Cebocephaly and sirenomelia are uncommon birth defects. Their association is extremely rare; however, the presence of spina bifida with both conditions is not unexpected. We report on a female still-birth with cebocephaly, alobar holoprosencephaly, cleft palate, lumbar spina bifida, sirenomelia, a single umbilical artery, and a 46,XX karyotype, but without maternal diabetes mellitus. Our case adds to the examples of overlapping cephalic and caudal defects, possibly related to vulnerability of the midline developmental field or axial mesodermal dysplasia spectrum.

Cutis marmorata telangiectatica congenita associated with an elevated maternal serum human chorionic gonadotrophin level and transitory isolated fetal ascites.

A 34-year-old woman with an abnormal maternal serum screening result and a Down syndrome risk of 1:60 calculated from a maternal serum alpha-fetoprotein (AFP) value of 1.4 multiples of the median (MoM) and a human chorionic gonadotrophin (hCG) level of 4.32 MoM at 18 weeks' gestation was found to have isolated fetal ascites at 23 weeks' gestation. Spontaneous resolution occurred 10 weeks after the initial presentation. After birth, the neonate had generalized cutis marmorata telangiectatica congenita (CMTC), large vascular plaques on the scalp with superficial ulceration and crusts, a small atrial septal defect, a patent ductus arteriosus, hepatomegaly, micrognathia, seizures, an abnormal electroencephalogram, congenital retinal detachment, glaucoma and widely spaced toes. Our patient illustrates that CMTC in utero may be associated with a markedly elevated maternal serum hCG level as well as transitory isolated fetal ascites. However, such associations can be coincidental and further collaborative studies and cases will be necessary before it can be determined that a disproportionately elevated hCG level and transitory isolated fetal ascites are predictive of CMTC in utero.

Progressive fetal axillary cystic lymphangioma with coexistent naevus flammeus.

We report the rare occurrence of a progressive fetal axillary cystic lymphangioma coexistent with an overlying naevus flammeus. The fetus at 22 weeks' gestation was found to have a 37 x 35 mm left axillary multiloculated mass without colour-flow imaging. Amniocentesis showed a normal 46,XX karyotype. Multiple fine-needle aspirations of the mass in the second and third trimesters obtained blood-stained chocolate-coloured fluid containing numerous erythrocytes and lymphocytes but proved ineffective in lessening the progressive growth of the mass. The mother underwent caesarean delivery and a healthy neonate was born with a 141 x 81 mm left axillary cystic lymphangioma and a 50 x 35 mm coexistent naevus flammeus. The neonate was well after simple excision of the lesions. Although cystic lymphangiomas arising in the axilla enlarge progressively during fetal life, our case suggests a good prognosis and except for genetic evaluation, no prenatal intervention is required.

In utero urinary bladder perforation, urinary ascites, and bilateral contained urinomas secondary to posterior urethral valves: clinical and imaging findings.

We report on a rare in utero appearance of urinary bladder perforation, urinary ascites, and bilateral contained urinomas secondary to posterior urethral valves. The findings on prenatal sonography, postnatal voiding cystourethrography, and magnetic resonance imaging are described.

Prenatal diagnosis, pathology, and genetic study of fetus in fetu.

We report the prenatal diagnosis, pathology, cytogenetics, and molecular studies of a retroperitoneal fetus in fetu. Prenatal ultrasonography of the host fetus in the third trimester showed an anencephalic, acardiac mass with identifiable extremities and spine within an intra-abdominal cystic mass. Pathological examination revealed a fetiform mass weighing 20 g with four extremities, digits, vertebral bodies, an oral cavity with developing teeth, primitive male external genitalia, a urinary bladder, a cloaca with an external opening, large intestines, a membranous capsule, and an umbilical cord with one artery, one vein, and Wharton's jelly. Histological examination demonstrated nerve bundles in the fibrocollagenous tissue below the cuboidal surface epithelium of the membranous capsule, and absence of lamina elastica interna and vasa vasorum in the single artery of the umbilical cord. Both the host infant and the fetus in fetu had a normal 46,XY karyotype. Molecular analysis using informative genetic markers showed no genetic difference between the host infant and the fetiform mass. We report this case as an unusual example of fetus in fetu in co-existence with an amnion-like membrane containing nerve bundles and with a well-formed umbilical cord. We demonstrate that fetus in fetu can be diagnosed prenatally if the fetiform mass has well-developed limbs and spine. We emphasize the necessity for suspicion of fetus in fetu when a well-defined encapsulated cystic mass with calcified solid components is detected prenatally in a fetus by ultrasonography.

First report of distal obstructive uropathy and prune-belly syndrome in an infant with amniotic band syndrome.

We describe the first report of distal obstructive uropathy and prune-belly syndrome in an infant with amniotic band syndrome. Prenatal ultrasonographic examination in the third trimester revealed intermittent oligohydramnios, bilateral hydronephrosis, and megacystis. Postnatally, the infant was found to have a scalp defect, a skin pedicle, pseudosyndactyly and constriction rings on the hands, marked distention of the abdomen, a fibrous band attached to the proximal urethra causing urethral stricture, a swollen penile shaft, bilateral talipes equinovarus, and syndactyly of the feet. Multiple fibrous amniotic bands could be identified in the placenta. Our case shows that fetal distal obstructive uropathy can be associated with the congenital constriction band syndrome.

Prenatal diagnosis of supernumerary der(22)t(11;22) associated with the Dandy-Walker malformation in a fetus.

We present the first report of prenatally diagnosed Dandy-Walker malformation with the karyotype of partial trisomy 11 and 22 due to familial translocation t(11;22)(q23;q11) inherited in three generations. We demonstrate that the Dandy-Walker malformation can be an associated congenital malformation of supernumerary der(22)t(11;22) syndrome and emphasize the importance of chromosomal analysis and genetic counselling in the obstetric management of prenatally diagnosed Dandy-Walker malformation.

Prenatal diagnosis of asphyxiating thoracic dysplasia (Jeune syndrome).

Asphyxiating thoracic dysplasia (ATD), or Jeune syndrome, is an uncommon autosomal recessive skeletal disorder characterized by a small thorax, varying degrees of rhizomelic brachymelia, polydactyly, pelvic abnormalities, and renal anomalies. We describe prenatal sonographic examinations in the third trimester of a fetus with abnormal small thorax, short limbs, polyhydramnios, and absence of fetal respiratory movements. At 36 weeks gestation, the fetal biparietal diameter was 93 mm, compatible with 37 weeks; the long-bone lengths measured < 5th percentile; the thoracic circumference (TC) measured 230 mm (< 5th percentile); the abdominal circumference (AC) measured 286 mm (25th percentile), and the TC/AC ratio was 0.80 (lower limit of normal). Our case shows that, although a discrepancy between gestational age and TC is prominent, TC/AC ratio may reach lower limit of normal in cases of fetal ATD, when fetal growth is compromised.

Prenatal diagnosis of terminal deletion 7q and partial trisomy 3p in fetuses with holoprosencephaly.

Chromosome aberrations, mendelian mutations and exogenous agents can cause holoprosencephaly. Therefore, etiologic evaluation of holoprosencephaly is necessary for obstetricians and genetic counselors, once a prenatal diagnosis of holoprosencephaly has been made. We present four pregnancies in three women in which routine sonographic examinations led to the prenatal diagnosis of holoprosencephaly. Prenatal cytogenetic analysis and fluorescence in situ hybridization demonstrated a 46,XY,del(7)(pter-->q32:) and a 46,XY,der(2)t(2;3)(q37;p21)pat karyotype respectively in two fetuses with cyclopia, and a 46,XX,der(2)t(2;3)(q37;p21)pat and a 46,XX,der(7)t(3;7)(p23;q36) karyotype respectively in two fetuses with premaxillary agenesis. In conclusion, terminal deletion 7q and partial trisomy 3p in holoprosencephalic fetuses indicates that genes contributing to craniofacial development reside in these critical regions. Proper prognostic evaluation in further pregnancies requires expertise in cytogenetics and genetic counseling.

A concealed penis mimicking penile agenesis in an infant with trisomy 13.

Penile agenesis results from failure in the development of the genital tubercle and is rarely associated with chromosomal abnormalities. We report on an echographic prenatal diagnosis of penile agenesis associated with trisomy 13. At birth, the contour of the penile shaft and the glans could not be seen. However, a careful palpation allowed us to determine that the penile shaft was concealed and normal in size, rather than penile agenesis being present. To our knowledge, a concealed penis associated with trisomy 13 has not previously been described.

Prenatal diagnosis and perinatal aspects of abdominal wall defects.

We retrospectively reviewed 27 cases of omphalocele and 15 cases of gastroschisis occurring among 62, 572 deliveries between 1987 and 1994. All cases had undergone prenatal sonographic examinations at a mean gestational age of 28 weeks. In cases of omphalocele, 59.3% (16/27) of fetuses were associated with multiple malformations and 16% (4/25) had chromosomal abnormalities. Among the 4 cases with an abnormal karyotype, three cases were associated with extracorporeal livers and two cases were associated with umbilical cord cysts. Prenatal ultrasound examinations during the second and third trimesters were able to detect 66.7% (18/27) of the cases of omphalocele and 66.7% (10/15) of the cases of gastroschisis. Failure in correctly diagnosing abdominal wall defects by prenatal ultrasound occurred mostly in cases associated with small defects, ruptured omphalocele, multiple fetal anomalies, intrauterine fetal death, twin pregnancies, or cases referred in late gestation. A comparison of perinatal data between omphalocele and gastroschisis reveals fetuses with omphalocele carry higher risks of associated malformations, chromosomal abnormalities, prematurity, and neonatal death. Although fetuses with gastroschisis have higher incidences of oligohydramnios and small for gestational age, the fetal prognosis after pediatric surgery is good.

Partial duplication of 3q and distal deletion of 11q in a stillbirth with an omphalocele containing the liver, short limbs, and intrauterine growth retardation.

We describe a female stillbirth with duplication of 3q21-->qter and deletion of 11q23-->qter resulting from an unbalanced segregation of a maternal t(3;11) reciprocal translocation. The proband had some of the clinical features consistent with those seen in patients with dup(3q) syndrome or distal del(11q) syndrome. Prenatal sonographic examination showed short limbs, intrauterine growth retardation, and an omphalocele containing the liver.