Yu Peng Liu

Autosomal recessive polycystic kidney disease: appearance on fetal MRI

Routine antenatal US of a 25-year-old woman at 34 weeks’ gestation demonstrated oligohydramnios, enlarged echogenic fetal kidneys and an empty urinary bladder. Autosomal recessive polycystic kidney disease (ARPKD) with poor prognosis was diagnosed. Because oligohydramnios impaired US imaging, a complementary MR study was performed. Fetal MRI using single-shot fast spin-echo (SSFSE) sequences demonstrated hypointensity of the lungs, oligohydramnios, symmetrical nephromegaly, and nonvisualization of renal pelves and urinary bladder. The enlarged well-demarcated kidneys with increased signal intensity suggested a high water content of the renal parenchyma, consistent with numerous dilated collecting ducts; a few tiny hyperintense cysts were also noted in both kidneys (Fig. 1) and the diagnosis of ARPKD was confirmed. Unfortunately, the baby died during delivery. The diagnosis of ARPKD was confirmed at autopsy. ARPKD is the most common heritable cystic renal disease occurring in infancy and childhood [1]. The primary modality for prenatal diagnosis in ARPKD is US, but there are difficulties in evaluating fetal anatomy when there is maternal obesity or oligohydramnios, which is common with urinary tract malformations [2]. Under these circumstances, fetal MRI with fast scanning techniques plays a complementary role in confirming the diagnosis and identifying other associated abnormalities [3].

Ventriculomegaly, Intrauterine Growth Restriction, and Congenital Heart Defects as Salient Prenatal Sonographic Findings of Miller-Dieker Lissencephaly Syndrome Associated With Monosomy 17p (17p13.2 → pter) in a Fetus

OBJECTIVEnTo present the prenatal sonographic findings of Miller-Dieker lissencephaly syndrome (MDLS) associated with monosomy 17p (17p13.2 --> pter) in a fetus.nnnCASE REPORTnA 25-year-old, gravida 3, para 1, woman was referred to Mackay Memorial Hospital at 36 weeks gestation because of ventriculomegaly, intrauterine growth restriction, and congenital heart defects detected by ultrasound. The pregnancy was uneventful until 32 weeks of gestation when ventriculomegaly was first noted. Level II ultrasound at 36 weeks gestation showed a fetal biometry equivalent to 32 weeks, tetralogy of Fallot, and bilateral ventriculomegaly. At 38 weeks gestation, a 2,308-g female baby was delivered with facial dysmorphism. A presumptive diagnosis of DiGeorge syndrome was made. However, no del22q11 could be detected by rapid fluorescence in situ hybridization analysis. Cytogenetic analysis of the cord blood revealed a 46,XX,del(17)(p13.2) karyotype. Brain ultrasound showed paucity of gyral and sulcal development. Computed tomography scans showed tetralogy of Fallot. Magnetic resonance imaging of the brain showed lissencephaly and colpocephaly. The final diagnosis was MDLS.nnnCONCLUSIONnVentriculomegaly and intrauterine growth restriction are important prenatal ultrasound markers of MDLS. Prenatal diagnosis of conotruncal heart defects in association with ventriculomegaly and intrauterine growth restriction should include a detailed investigation of MDLS in addition to DiGeorge syndrome.

Rapid aneuploidy diagnosis of trisomy 18 by array comparative genomic hybridization using uncultured amniocytes in a pregnancy with fetal arachnoid cyst detected in late second trimester

Department of Medicine, Mackay Medical College, New Taipei City, Taiwan Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan Department of Biotechnology, Asia University, Taichung, Taiwan e School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan f Institute of Clinical and Community Health Nursing, National Yang-Ming University, Taipei, Taiwan Department of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, Taipei, Taiwan Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Hsinchu, Taiwan Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan Department of Medical Research, China Medical University Hospital, Taichung, Taiwan Department of Radiology, Mackay Memorial Hospital Hsinchu Branch, Hsinchu, Taiwan Mackay Medicine, Nursing and Management College, Taipei, Taiwan Department of Bioengineering, Tatung University, Taipei, Taiwan

Prenatal Diagnosis of Rhabdomyomas and Cerebral Tuberous Sclerosis by Magnetic Resonance Imaging in One Fetus of a Dizygotic Twin Pregnancy Associated With a Frameshift Mutation in the TSC2 Gene

A 28-year-old woman, gravida 3, para 0, was referred to our hospital at 30 weeks of gestation for evaluation of cardiac tumors in one fetus of a twin pregnancy. The woman had not undergone any assisted reproductive technology. She and her husband were healthy and had no family history of tuberous sclerosis complex (TSC) or cardiac tumors. Previous sonographic examination had revealed a dichorionic and diamniotic twin pregnancy. Detailed sonographic examination of the fetuses demonstrated a normal heart in one male co-twin and multiple rhabdomyomas in the left ventricle (LV) in the other male co-twin. The affected co-twin had six intracardiac tumors, including three tumors measuring 1.87× 1.42 cm, 1.12×1.04 cm and 0.84×1.00 cm, respectively in the inlet of the LV, a 1.41 × 0.74-cm tumor in the apex of the LV, and a 0.52 × 1.12-cm tumor in the LV side of the interventricular septum near the apex. There was no significant regurgitation and color Doppler mapping showed adequate flow in the LV and right ventricle. Ultrafast magnetic resonance imaging revealed small subependymal tubers (Figure 1A) and cardiac rhabdomyomas arising from the interventricular septum and the lateral wall of the LV (Figure 1B) in the affected co-twin. Fetal growth and amniotic fluid volume were normal. The unaffected co-twin (2,344 g) and affected co-twin (2,818 g) were delivered uneventfully by cesarean section at 37 weeks of gestation because of malpresentation. Neonatal computed tomography scans of the affected infant demonstrated small subependymal tubers (Figure 2A) and intracardiac rhabdomyomas in the LV (Figure 2B). The results of brain and renal ultrasound were unremarkable. The infant’s ventricular outlet was not obstructed, and his cardiac function remained within normal limits. Cytogenetic analysis of cord blood from the twins revealed a karyotype of 46,XY. A zygosity test showed dizygosity. Molecular analysis of cord blood from the affected co-twin revealed a de novo frameshift mutation in the TSC2 gene or TSC2 exon 33 c.4472_ 4473delAA (Figure 3). No such mutation was detected by DNA analysis in the parents or the unaffected co-twin. The affected infant was doing well at 2 years of age, with no episodes of seizures or cardiac discomfort. The cardiac tumors persisted but became smaller in size. Prenatal magnetic resonance imaging has been shown to be a useful adjunct to ultrasound for the precise determination of the extent of cerebral involvement in TSC [1–4]. TSC is caused by mutations in the tumor suppressor genes TSC1 and TSC2. The TSC1 gene (OMIM 605284) maps to chromosome 9q34 and encodes the protein hamartin, while the TSC2 gene (OMIM 191092) maps to chromosome 16p13.3 and PRENATAL DIAGNOSIS OF RHABDOMYOMAS AND CEREBRAL TUBEROUS SCLEROSIS BY MAGNETIC RESONANCE IMAGING IN ONE FETUS OF A DIZYGOTIC TWIN PREGNANCY ASSOCIATED WITH A FRAMESHIFT MUTATION IN THE TSC2 GENE

Persistent cloaca presenting with a perineal cyst: Prenatal ultrasound and magnetic resonance imaging findings

A 40-year-old, primigravid woman presented at 23 weeks of gestation for evaluation of an extra-abdominal echogenic cystic mass of the fetus. Amniocentesis revealed a karyotype of 46,XX. Prenatal ultrasound showed a two-vessel umbilical cord, hydrocolpos, and distended bladder, urethra, and colon, and a perineal cystic mass. The kidneys and amniotic fluid amount were normal. Fetal magnetic resonance imaging revealed ascites, hydrocolpos, distended urinary bladder and colon, high rectum, and a perineal cyst. The fetus postnatally manifested persistent cloaca. The perineum was distended and smooth, without patent anal, vaginal, and urethral openings. The external genitalia were ambiguous with no labia majora, labia minora, or clitoris. The perineal cyst had a very small single orifice. We suggest that cloacal anomalies be considered in any female fetus with hydrocolpos, distended bladder and colon, ascites, and a perineal cyst.

Chromosome 15q overgrowth syndrome: Prenatal diagnosis, molecular cytogenetic characterization, and perinatal findings in a fetus with dup(15)(q26.2q26.3)

OBJECTIVEnTo present molecular cytogenetic characterization of a prenatally detected duplication of 15q26.2→q26.3 in a fetus with overgrowth.nnnCASE REPORTnA 34-year-old para 0 woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a derivative chromosome 15, or der(15), with additional material at the end of the long arm of one chromosome 15. Parental karyotypes were normal. Fetal overgrowth was first noted at 21 weeks of gestation. Repeated amniocentesis was performed at 22 weeks of gestation. Array comparative genomic hybridization revealed a 4.71-Mb duplication from 15q26.2 to 15q26.3 encompassing the IGF1R gene. Fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone probes specific for 15q26.2-q26.3 and the subtelomeric region of 15q showed a direct duplication and no terminal deletion in the der(15). Polymorphic DNA marker analysis determined a paternal origin of the duplication of 15q. Level II ultrasound at 23 weeks of gestation revealed a fetal biometry equivalent to 26 weeks. The pregnancy was subsequently terminated, and a 1062-g (>99(th) centile) malformed fetus was delivered at 24 weeks of gestation with craniofacial dysmorphism, craniosynostosis, and overgrowth.nnnCONCLUSIONnThe present case provides evidence for prenatal overgrowth, craniosynostosis, and characteristic facial dysmorphism in association with a duplication of 15q26.2→q26.3 and a duplication of the IGF1R gene. Prenatal diagnosis of fetal overgrowth should include a differential diagnosis of the chromosome 15q overgrowth syndrome.

Prenatal Diagnosis of Persistent Cloaca With Hydrometrocolpos and Ascites by Magnetic Resonance Imaging in One Fetus of a Dizygotic Twin Pregnancy

A 34-year-old primigravid woman presented at 29 weeks of gestation for evaluation of fetal ascites and an intraabdominal echogenic cystic mass (Figure 1) in one twin of a twin pregnancy. The woman had not undergone any assisted reproductive technology. Aspiration of the ascites and the cystic mass revealed multiple epithelial cells and cytogenetic analysis demonstrated a 46,XX karyotype in the affected co-twin. Ultrasound following aspiration showed a distended vagina connecting to the uterine cavity and compressing the urinary bladder (Figure 2). Ultrafast magnetic resonance imaging (MRI) of the affected co-twin revealed massive ascites, a compressed urinary bladder, a distended vagina, a dilated uterus, and a dilated distal colon, consistent with a diagnosis of persistent cloaca with hydrometrocolpos and ascites (Figure 3). The unaffected co-twin (1,306 g) and affected co-twin (2,108 g) were delivered uneventfully by cesarean section at 31 weeks of gestation. Both twins had a karyotype of 46,XX. A zygosity test determined dizygosity. The affected co-twin had meconium peritonitis, urinary ascites, and a persistent cloaca. The urinary, genital, and intestinal tracts converged into a cloacal canal with a single opening at the perineum. The ascites was caused by drainage of the urine into the abdominal cavity via the vagina, the uterus and the Fallopian tubes, as well as by irritation of the peritoneum by urine and meconium. Hydrometrocolpos was caused by fluid accumulation resulting from distal vaginal obstruction through backward pressure from the cloacal canal. The hydrometrocolpos compressed the bladder causing partial bladder outlet obstruction. Dilation of the distal colon was caused by direct compression from the hydrometrocolpos and narrowing of the rectal communication. The affected infant was doing well at 1 year and 6 months of age, after corrective reconstructive surgery. A persistent cloaca results from failure or maldevelopment of the urorectal septum that divides the urogenital sinus and anorectal canal [1]. Hydrometrocolpos

Prenatal Magnetic Resonance Imaging, Ultrasound Imaging Findings and Genetic Analysis of Concomitant Rhabdomyomas and Cerebral Tuberous Sclerosis

A 32-year-old, gravida 3, para 1, woman had an uncomplicated pregnancy until 29 weeks’ gestation when multiple fetal cardiac tumors were detected on routine ultrasound. She had experienced one abortion. Her first child was a 3-year-old healthy boy. This was her third pregnancy. She and her husband were healthy and did not have any family history of tuberous sclerosis complex (TSC) or cardiac tumors. Detailed sonographic examination of the fetal heart demonstrated seven cardiac rhabdomyomas including a 0.89 × 0.44 cm tumor in the lowest part of the interventricular septum (IVS) near the apex, a 0.84 × 0.64 cm tumor in the upper part of the IVS near the crus, a 0.34 × 0.20 cm tumor in the middle part of the IVS, two tumors measuring 0.37 × 0.30 cm and 0.30 × 0.18 cm in the lateral wall of the left ventricle, a 0.49 × 0.33 cm tumor in the lateral wall of the left ventricle near the aortic valve, and a 0.35 × 0.24 cm tumor in the lateral wall of the left atrium (Figure 1). Detailed sonographic examination of the fetal brain also demonstrated several suspicious echogenic foci around the cerebral ventricles (Figure 2). Ultrafast magnetic resonance imaging (MRI) revealed small subependymal

Galloway-Mowat syndrome: Prenatal ultrasound and perinatal magnetic resonance imaging findings

OBJECTIVEnTo present prenatal ultrasound and perinatal magnetic resonance imaging (MRI) findings of Galloway-Mowat syndrome.nnnCASE REPORTnA 31-year-old woman, gravida 3, para 2, was referred for genetic counseling at 29 weeks of gestation because of abnormal ultrasound findings and a previous child with Galloway-Mowat syndrome. During this pregnancy, microcephaly, intrauterine growth restriction (IUGR), and oligohydramnios were first noted at 27 weeks of gestation. Repeated ultrasounds showed microcephaly, IUGR, and oligohydramnios. MRI performed at 32 weeks of gestation showed reduced sulcation of the brain, pachygyria, poor myelination of the white matter, and cerebellar atrophy. A diagnosis of recurrent Galloway-Mowat syndrome was made. At 40 weeks of gestation, a 2,496-g female baby was delivered with microcephaly, a narrow slopping forehead, epicanthic folds, microphthalmos, a highly arched palate, a small midface, a beaked nose, thin lips, large low-set floppy ears, clenched hands, and arachnodactyly. Postnatal MRI findings were consistent with the prenatal diagnosis. Renal ultrasound showed enlarged bilateral kidneys with increased echogenicity. At the age of 2 weeks, the infant became edematous and developed nephrotic syndrome.nnnCONCLUSIONnMicrocephaly, IUGR, and oligohydramnios are significant ultrasound triad of fetal Galloway-Mowat syndrome. Prenatal ultrasound diagnosis of microcephaly, IUGR, and oligohydramnios in late second trimester or in early third trimester should alert clinicians to the possibility of Galloway-Mowat syndrome and prompt a detailed search of abnormal sulcation, cortical gyral maldevelopment, and cerebellar atrophy by fetal ultrafast MRI.

APERT SYNDROME ASSOCIATED WITH UPPER AIRWAY OBSTRUCTION AND GASTROESOPHAGEAL REFLUX INDUCING POLYHYDRAMNIOS IN THE THIRD TRIMESTER

Here, we present the case of a female infant, the firstchild of a 32-year-old woman and a 45-year-old man,who were healthy and non-consanguineous. The familyhistory was unremarkable. The infant was delivered at37 weeks’ gestation with a birth weight of 2,834g. Shehad midface hypoplasia, cleft palate, low-set ears, andbilateral syndactyly of the hands and feet (Figures 1–3).She had a 46,XX karyotype. DNA testing for Apert syn-drome revealed a heterozygous c.755 C >G, TCG >TGGtransversion leading to a Ser252Trp (S252W) mutationin the fibroblast growth factor receptor 2 (