Nonisolated diaphragmatic hernia in Simpson-Golabi-Behmel syndrome.

OBJECTIVE: Congenital diaphragmatic hernia (CDH) is associated with Simpson-Golabi-Behmel syndrome (SGBS), but few cases diagnosed prenatally have been reported. The aim of this series is to highlight the association of nonisolated CDH with SGBS type I on prenatal ultrasound and emphasize the importance of genetic testing, fetal autopsy, and family history in confirming this diagnosis. METHOD: Retrospective review of 3 cases of SGBS type I in a single tertiary care centre. Family history, fetal ultrasound, autopsy findings, and genetic testing for GPC3 was performed for each case. RESULTS: Fetal ultrasound findings in the second trimester were CDH, omphalocele, increased nuchal fold, renal anomaly, and cleft lip and palate. Fetal autopsy confirmed the prenatal ultrasound findings and also showed dysmorphic facial features and premalignant lesions on renal and gonadal histology. Microarray and DNA analysis of the GPC3 gene confirmed the diagnosis of SGBS type I in each case. CONCLUSION: Nonisolated CDH in a male fetus suggests a diagnosis of SGBS type I. Fetal autopsy, pedigree analysis, and genetic testing for GPC3 are all essential to confirming the diagnosis. The histological findings of ovotestes and nephroblastomatosis indicate that cancer predisposition is established early in fetal life.

Prospective study of intracranial translucency and the posterior brain in normal fetuses at the 11- to 13-week scan.

OBJECTIVES: To evaluate the ability of sonographers to prospectively identify intracranial translucency and posterior brain structures at 11 to 13 weeks and to evaluate measurement reproducibility of brain stem and brain stem-occipital bone diameters on stored images. METHODS: After specific training for intracranial translucency visualization, 10 nonphysician sonographers prospectively identified intracranial translucency at the 11- to 13-week scan, noting whether intracranial translucency was present, absent, or uncertain. If absent/uncertain, they documented the reason as spina bifida or an inadequate image (with reasons for the inadequate image). Measurements of brain stem and brain stem-occipital bone diameters were performed on stored images. Fifty randomly selected cases were reviewed for intraobserver and interobserver variability. RESULTS: In 313 singleton pregnancies, the posterior brain including intracranial translucency was evaluated; 293 (93.6%) had known pregnancy outcomes. None had open spina bifida, but 7 had chromosomal or congenital abnormalities. In the remaining 286 normal fetuses, intracranial translucency was seen in 275 (96%) and uncertain in 11 (4%), due to inadequate images (top 3 reasons were fetal position [n = 8], obesity [n = 5], and retroverted uterus [n = 4]). Fetal position and gestational age were significantly associated with intracranial translucency visualization (P < .05). Intraobserver and interobserver agreement rates were moderate for measurements of brain stem diameter (intraclass correlation coefficients, 0.59 and 0.57) and substantial for brain stem-occipital bone diameter (intraclass correlation coefficients, 0.76 and 0.61). Bland-Altman analysis revealed negligible intraobserver and interobserver differences in brain stem and brain stem-occipital bone diameter measurements. CONCLUSIONS: Intracranial translucency can be prospectively identified by trained sonographers in 96% of normal fetuses at 11 to 13 weeks. Measurements of brain stem and brain stem-occipital bone diameters are reproducible.

Fetal ventriculomegaly secondary to isolated large choroid plexus cysts: prenatal findings and postnatal outcome.

OBJECTIVE: To report the prenatal findings and postnatal outcome of fetal ventriculomegaly associated with isolated large choroid plexus cysts (CPCs). METHOD: Cases of isolated fetal ventriculomegaly and large CPCs (>10 mm) were identified through a search of patient records from 2003 to 2006. Ultrasound (US) findings were reviewed: unilateral or bilateral ventriculomegaly, ventricular size, size of CPCs, and changes on serial scans. Correlation was made with fetal magnetic resonance imaging (MRI), pregnancy outcome, and long-term follow-up. RESULTS: Six cases of isolated large CPCs (12-30 mm) with ventriculomegaly (11-17 mm) were detected on US at 18 to 26 weeks of gestation. Serial prenatal US showed the CPCs resolved (one case) or decreased in size (five cases). Ventricular size became normal during pregnancy in five cases and decreased in size in one case. Fetal MRI performed in three cases showed no additional findings. Five patients had amniocentesis which showed normal karyotype. There was one termination of pregnancy (the fetus showed no abnormality on external examination). There were five healthy newborns, with follow-up to 4.5 years of age (one), 5.5 years (one), and 6 years (three). All had normal physical and developmental outcome. CONCLUSION: Large isolated CPCs may transiently dilate the fetal cerebral ventricles. Follow-up to 6 years has shown normal growth and development.

Fetal anatomic survey using three-dimensional ultrasound in conjunction with first-trimester nuchal translucency screening.

OBJECTIVE: To determine the visualization rates of fetal anatomic structures by three-dimensional ultrasound (3DUS) at 12-13 weeks of gestation. STUDY DESIGN: This was a prospective observational study of women presenting for nuchal translucency ultrasound. Five 3D volumes of the fetus were acquired transabdominally. Two investigators independently reviewed the stored volumes offline following a standardized protocol. RESULTS: One hundred singleton fetuses were examined. The mean time for 3D volumes acquisition was 4.8 min; and for 3D review 17 min. Anatomic structures were seen as follows: cranium, lateral cerebral ventricles and abdominal wall 100%; stomach, vertebrae, upper and lower limbs >or= 94%; face 71%, bladder 58%, both kidneys 39%, skin overlying spine 26% and heart 18%. Agreement between two observers ranged from 100% (for head, abdominal wall and lower limbs) to 43% (for visualization of skin overlying spine). A complete basic anatomic survey was achieved in 11.4% of the 12-week fetuses and 33.3% of the 13-week fetuses (p-value = 0.038). CONCLUSIONS: First-trimester transabdominal 3DUS was adequate for assessment of the head, abdominal wall, stomach, limbs and vertebral alignment. It was less effective for evaluating the heart and intactness of the skin over the spine.

Malformations of the fetal dural sinuses.

BACKGROUND: Dural sinus malformation (DSM) is a term used to describe congenital vascular malformations characterized by massive dilation of one or more dural sinuses: these dilatations are typically associated with arteriovenous shunts. Such malformations can present antenatally but their early natural history and anatomy is poorly defined. METHODS: We reviewed five years of autopsy experience and retrieved three primary vascular malformations of the fetal dural sinuses with ultrasound, magnetic resonance imaging (MRI) and post-mortem correlation. RESULTS: Fetal ultrasound and MRI obtained between 19 and 23 weeks gestational age demonstrated in all cases dilation of the dural sinuses. In two cases vascular thromboses were present in either the dilated dural sinus (one of three) or the associated arteriovenous fistula (one of three). All cases were autopsied at 22-23 weeks gestational age. In one there was imaging and autopsy evidence of remodeling of the dural sinuses associated with a pial arteriovenous fistula. In two cases, no arteriovenous malformation was identified on initial imaging, but only became evident at autopsy. One case showed morphological overlap with vein of Galen aneurysmal malformation, with a midline arteriovenous shunt and vein of Galen ectasia. The other demonstrated a perisylvian dural arteriovenous fistula. CONCLUSION: In utero thrombosis of feeding vascular malformations or of the dural sinus malformation may be prominent. The early in utero developmental trajectory of dural sinus malformation (DSM) is poorly defined and deserves further study.

MRI and (1)H MRS of the breast: presence of a choline peak as malignancy marker is related to K21 value of the tumor in patients with invasive ductal carcinoma.

To assess which specific morphologic features, enhancement patterns, or pharmacokinetic parameters on breast Magnetic Resonance Imaging (MRI) could predict a false-negative outcome of Proton MR Spectroscopy ((1)H MRS) exam in patients with invasive breast cancer. Sixteen patients with invasive ductal carcinoma of the breast were prospectively included and underwent both, contrast-enhanced breast MRI and (1)H MRS examination of the breast. The MR images were reviewed and the lesions morphologic features, enhancement patterns and pharmacokinetic parameters (k21-value) were scored according to the ACR BI-RADS-MRI lexicon criteria. For the in vivo MRS studies, each spectrum was evaluated for the presence of choline based on consensus reading. Breast MRI and (1)H MRS data were compared to histopathologic findings. In vivo (1)H MRS detected a choline peak in 14/16 (88%) cancers. A false-negative (1)H MRS study occurred in 2/16 (14%) cancer patients. K21 values differed between both groups: the 14 choline positive cancers had k21 values ranging from 0.01 to 0.20/second (mean 0.083/second), whereas the two choline-negative cancers showed k21 values of 0.03 and 0.05/second, respectively (mean 0.040/second). Also enhancement kinetics did differ between both groups; typically both cancers that were choline-negative showed a late phase plateau (100%), whereas this was only shown in 5/14 (36%) of the choline positive cases. There was no difference between both groups with regard to morphologic features on MRI. This study showed that false-negative (1)H MRS examinations do occur in breast cancer patients, and that the presence of a choline peak on (1)H MRS as malignancy marker is related to the k21 value of the invasive tumor being imaged.

Prenatal US and MR imaging findings of lissencephaly: review of fetal cerebral sulcal development.

The cerebral cortex develops in three overlapping stages: cell proliferation, neuronal migration, and cortical organization. Abnormal neuronal migration may result in lissencephaly, which is characterized by either the absence (agyria) or the paucity (pachygyria) of cerebral convolutions. The two main clinicopathologic types of lissencephaly may be differentiated according to their prenatal imaging features. Other cranial and extracranial abnormalities also may occur in association with lissencephaly. The prognosis is often poor, but prenatal diagnosis allows appropriate counseling and optimization of obstetric management. Familiarity with the normal ultrasonographic (US) and magnetic resonance (MR) imaging appearances of the fetal cerebral cortex at various stages of gestation is essential for the early detection of abnormal sulcal development. The primary fissures and sulci that can be examined with prenatal US and MR imaging include the parieto-occipital fissure, calcarine fissure, cingulate sulcus, convexity sulci, and sylvian fissure and insula.

Detection of fetal structural abnormalities with US during early pregnancy.

Ultrasonography (US) is performed during early pregnancy for dating, determination of the number of fetuses, assessment of early complications, and increasingly for evaluation of the fetus, including measurement of the thickness of the nuchal translucency (NT). Measurement of NT thickness between 11 and 14 weeks gestation, combined with maternal age and maternal serum biochemistry, can be an effective method of screening for trisomy 21 and other chromosomal abnormalities. Furthermore, an increased NT thickness in the presence of a normal karyotype is associated with an increased frequency of structural defects and genetic syndromes. Therefore, this finding is an indication for a more detailed anatomic survey of the fetus. Besides nuchal abnormalities, a wide range of other congenital anomalies can be diagnosed with US at 11-14 weeks gestation, including defects of the central nervous system, heart, anterior abdominal wall, urinary tract, and skeleton. The anatomic survey can be performed with a standardized protocol by using transabdominal US and, when necessary, transvaginal US. A thorough knowledge of the US features of normal fetal development is necessary to avoid potential diagnostic pitfalls.

Colour Doppler ultrasound assessment of the normal neonatal hip.

OBJECTIVE: To determine the morphology and hemodynamic characteristics of the arterial vessels of the proximal femur according to specific anatomic regions in asymptomatic neonates in 2 pediatric-based health care institutions. METHODS: Forty-three neonates (29 female, 14 male; age range, 2 d-3 mo; median age, 3 d) were enrolled in the study. Thirty-two (37%) of 86 hips were classified as Graf type IIA joints (mean alpha angle, 56.0 degrees +/- 2.7 degrees ), and 54 (63%) were classified as type I joints (mean alpha angle, 65.0 degrees +/- 4.6 degrees ). RESULTS: Colour and spectral Doppler imaging identified vessels running along the acetabular labrum, epiphyseal vessels, and femoral neck. We showed 4 different patterns of vascularity of the hips: radial, parallel, mixed radial-parallel, and indeterminate, however, they were not related to the hip maturity (P = .3, coronal plane; P = .62, transverse plane) or to the amount of colour pixels identified in each region (P = .35). The mean number of pixels in the ligamentum teres region was significantly higher than that in other regions of interest (P = .03). Except for the acetabular labrum arteries, Doppler spectrum waveforms of proximal femur arteries presented with low resistivity. There was a tendency towards females' acetabular arteries presenting with lower peak systolic velocities than males' acetabular arteries (P = .06). CONCLUSIONS: Colour Doppler spectrum waveforms and intensity of vascularity in normal neonatal hips differ according to the anatomic region under evaluation. This observation deserves further investigation on its role on the physiopathogenesis of neonatal hip disorders.

First trimester ultrasound diagnosis of lethal multiple pterygium syndrome.

OBJECTIVE: Diagnosis of lethal multiple pterygium syndrome in the first trimester of pregnancy. METHODS: A 38-year-old woman attended our ultrasound (US) clinic at 11.2 weeks gestation. She has had two previous stillbirths affected by lethal multiple pterygium syndrome. Transabdominal and transvaginal US were performed and identified a recurrence. Autopsy findings are compared to the fetal US findings. RESULTS: Fetal US showed a markedly increased nuchal translucency, fixed flexion deformities of the elbows and knees bilaterally, cutaneous webs across both elbow joints and absent fetal movements. The patient decided to terminate the pregnancy and a D&C was performed. Pathology of intact fetal parts showed flexion deformity of the right elbow with a cutaneous web, and ulnar deviation of the right wrist. CONCLUSION: Increased nuchal translucency, absent limb movements, multiple joint contractures and cutaneous webs on US allowed the diagnosis of lethal multiple pterygium syndromes in the first trimester of pregnancy.

X-Linked dominant chondrodysplasia punctata: prenatal diagnosis and autopsy findings.

OBJECTIVE: To report our experience of the prenatal diagnosis of X-linked dominant chondrodysplasia punctata (CDPX2) and highlight its variable phenotypic presentation. METHODS: We report the sonographic features of three female fetuses affected with CDPX2. The ultrasound, radiographic and pathological findings were compared. RESULTS: Family 1: Two affected pregnancies, both terminated. Fetus 1: Presented with epiphyseal stippling involving the vertebrae, upper and lower limbs, asymmetric shortening of the long bones and flat facial profile. Fetus 2: Prenatal findings included premature epiphyseal stippling, paravertebral cartilaginous calcific foci, mild shortening of the long bones and flat facies. Mutation analysis of the mother and both fetuses revealed mutation in the emopamil-binding protein (EBP) gene. Family 2: Prenatal sonography showed scattered epiphyseal stippling, minimal vertebral segmentation anomalies, mild asymmetric limb shortening and flat facies. Female infant delivered at 39 weeks of gestation. Biochemical analysis in all three fetuses showed increased levels of serum 8(9)-cholestenol consistent with delta (8), delta (7)-isomerase deficiency and CDPX2. CONCLUSION: Prenatal diagnosis of CDPX2 is difficult because of marked phenotypic variation. Epiphyseal stippling, ectopic paravertebral calcifications, asymmetric shortening of long bones and dysmorphic flattened facies are crucial for prenatal diagnosis. DNA analysis of the CDPX2 gene and biochemical determination of the serum 8(9)-cholestenol level are important for diagnosis, especially if future pregnancies are planned.

Ultrasound detection of fetal anomalies in conjunction with first-trimester nuchal translucency screening: a feasibility study.

OBJECTIVE: The purpose of this study was to determine the effectiveness of a fetal anatomy survey in conjunction with first-trimester nuchal translucency (NT) screening ultrasound in an unselected pregnant population performed by sonographers. STUDY DESIGN: This was a prospective observational study of women presenting for NT screening for chromosomal defects. An anatomic survey was performed after a standardized protocol with a maximum scan time of 30 minutes. RESULTS: Three hundred twenty-five singleton fetuses (11+0 to 13+6 weeks) were examined and pregnancy outcome was available for 300 (92.3%) of cases. In 89 (24.6%) cases, transvaginal ultrasound was performed. The following fetal structures were seen in 95% of cases: cranium and intracranial anatomy, face, cord insertion, stomach, and all 4 limbs. The bladder was visualized in 89.5% of cases, the cardiac 4 chamber view in 84%, and the spine in only 45% of cases. Complete anatomy was seen in 109 (33%). Crown rump length greater than 55 mm and sonographer experience were important factors contributing to anatomic visibility. Of a total of 6 congenital defects in this cohort, 1 was detected in the first trimester (neural tube defect), 4 at the 18- to 20-week anatomic scan, and 1 postnatally. CONCLUSION: A complete anatomy survey was successful in 33% of first-trimester fetuses in a time-limited sonographer based screening program. Since some anomalies are not evident in the first trimester, the 18- to 20-week scan remains the gold standard.

Cavum veli interpositi: prenatal diagnosis and postnatal outcome.

We describe the finding of cavum veli interpositi (CVI) on fetal ultrasound and MRI and the postnatal MRI and developmental follow-up in two cases. The first case was diagnosed on fetal ultrasound at 33 weeks' gestation and confirmed on fetal MRI. No abnormalities were detected on postnatal examinations and the brain MRI at 1 year of age showed no changes. At 4 years of age, his growth and development were normal.The second case was diagnosed with CVI on fetal ultrasound and MRI at 33.5 weeks' gestation. Postnatal examination showed no abnormalities, and brain MRI at 8 months of age revealed that the CVI was unchanged, but there was a dilated cavum septum pellucidum and cavum vergae. Her growth and development during the first 4 years of life were normal. CVI is a rare fetal ultrasound finding, which seems to be benign. However, further neurodevelopmental follow-up is needed to confirm this observation.

Transvaginal US and hysterosonography in postmenopausal women with breast cancer receiving tamoxifen: correlation with hysteroscopy and pathologic study.

Tamoxifen citrate therapy increases the prevalence of benign and malignant uterine lesions. At transvaginal ultrasonography (US), the finding of a thickened central endometrial complex, with or without cystic changes, is often nonspecific and may be caused by an endometrial polyp, submucosal leiomyoma (fibroid), endometrial hyperplasia, carcinoma, or cystic atrophy. In addition, because of an increased prevalence of adenomyosis or adenomyosis-like changes in women receiving tamoxifen, proper transvaginal US assessment of endometrial thickness and abnormalities is difficult in some women. Hysterosonography, as an adjunct to transvaginal US, allows identification of intracavitary lesions and focal and diffuse endometrial abnormalities and helps determine whether an abnormality is endometrial or subendometrial. Endometrial polyps may be seen at transvaginal US as nonspecific thickening of the endometrial complex, with or without cystic changes. At hysterosonography, they appear as an echogenic mass with smooth margins. Submucosal leiomyomas may protrude into the endometrial cavity, causing false endometrial thickening at transvaginal US. Hysterosonography shows a round structure arising from the myometrium with a thin, overlying endometrium. At transvaginal US, when the endometrium cannot be accurately measured or when there is a nonspecific thickened central endometrial complex, hysterosonography can provide additional information and can help in the triage for hysteroscopic versus nondirected endometrial biopsy. Correlation of transvaginal US and hysterosonographic findings with hysteroscopic and pathologic findings enhances understanding of these changes, as well as the limitations and potential pitfalls of both imaging techniques.