Prenatal diagnosis of intestinal nonrotation using magnetic resonance imaging: Is it possible?

BACKGROUND: Malrotation of the bowel refers to any variation in the rotation and fixation of the gastrointestinal tract during the first trimester and is most commonly detected postnatally. Nonrotation of the bowel and incomplete rotation of the bowel are subtypes of malrotation. OBJECTIVE: To determine if the nonrotation subtype of malrotation of the bowel can be detected on prenatal magnetic resonance imaging (MRI). MATERIALS AND METHODS: Cases from 2012 to 2018 with nonrotation of the bowel without obstruction confirmed by imaging, surgery and/or autopsy were compared to prenatal imaging. Prenatal imaging was retrospectively reviewed to determine if prenatal diagnosis of malrotation could be made. Exclusion criteria included diaphragmatic hernia, omphalocele and gastroschisis. RESULTS: Ten cases of nonrotation diagnosed postnatally by upper gastrointestinal series (upper GI)/small bowel follow-through (SBFT) or autopsy had prenatal MRI. Prenatal MR studies were performed for assessment of heterotaxy syndrome with congenital heart disease (6/10), congenital heart disease with additional anomalies (suspected VACTERL [vertebral, anorectal, cardiac, tracheoesophageal, renal, limb] and suspected lung agenesis, ventriculomegaly) (3/10) and skeletal dysplasia (1/10). Eight upper GI/SBFT cases demonstrated nonrotation of the bowel without obstruction with the small bowel completely on one side of the abdomen contralateral to the stomach and the colon ipsilateral to the stomach; four cases were confirmed by surgery. The small bowel in one upper GI/SBFT case was unilateral contralateral to the stomach with a meandering colon. One case had nonrotation diagnosed at autopsy. There were no cases of postnatal midgut volvulus. Retrospective review of the 10 cases had prenatal MRI performed between 23 and 37 weeks of gestation. The coronal plane was the most optimal plane to assess the position of the stomach, small bowel and colon in relationship to each other. The small bowel was best assessed on T2-weighted images while the colon was best assessed on T1-weighted images. A nonrotated position of the small bowel was present in all 10 fetal MRI cases mirroring postnatal findings, with the small bowel contralateral to the stomach in 9/10 cases and ipsilateral to the stomach (in the right abdomen) in 1/10 cases. The colon was visualized by prenatal MRI in 9/10 cases, with 1 case limited due to a lack of T1-weighted imaging. A nonrotated position of the colon contralateral to the small bowel was present in 7/9 cases. In 2/9 cases, the colon was wandering, positioned on both sides of the midline. Colonic position in all nine cases matched postnatal findings. No cases presented with prenatal bowel obstruction. CONCLUSION: Detection of nonrotation of the bowel is possible on prenatal MRI.

Pediatric contrast-enhanced ultrasound: shedding light on the pursuit of approval in the United States.

For two decades, pediatric contrast US has been well accepted throughout Europe and other parts of the world outside the United States because of its high diagnostic efficacy and extremely favorable safety profile. This includes intravenous (IV) administration, contrast-enhanced US (CEUS) and the intravesical application, contrast-enhanced voiding urosonography (ceVUS). However, the breakthrough for pediatric contrast US in the United States did not come until 2016, when the U.S. Food and Drug Administration (FDA) approved the first pediatric indication for a US contrast agent. This initial approval covered the use of Lumason (Bracco Diagnostics, Monroe Township, NJ) for the evaluation of focal liver lesions via IV administration in children. A second pediatric indication followed shortly thereafter, when the FDA extended the use of Lumason for assessing known or suspected vesicoureteral reflux via intravesical application in children. Both initial pediatric approvals were granted without prospective pediatric clinical trials, based instead on published literature describing favorable safety and efficacy in children. Three years later, in 2019, the FDA approved Lumason for pediatric echocardiography following a clinical trial involving a total of 12 subjects at 2 sites. The story of how we achieved these FDA approvals spans more than a decade and involves the extraordinary dedication of two professional societies, namely the International Contrast Ultrasound Society (ICUS) and the Society for Pediatric Radiology (SPR). Credit also must be given to the FDA staff for their commitment to the welfare of children and their openness to compelling evidence that contrast US is a safe, reliable, radiation-free imaging option for our pediatric patients. Understanding the history of this approval process will impact the practical application of US contrast agents, particularly when expanding off-label indications in the pediatric population. This article describes the background of the FDA's approval of pediatric contrast US applications to better illuminate the potential pathways to approvals of future indications.

Fourteen-year follow-up of a child with acroscyphodysplasia with emphasis on the need for multidisciplinary management: a case report.

BACKGROUND: Acroscyphodysplasia has been described as a phenotypic variant of acrodysostosis type 2 and pseudohypoparathyroidism. In acrodysostosis, skeletal features can include brachydactyly, facial hypoplasia, cone-shaped epiphyses, short stature, and advanced bone age. To date, reports on this disorder have focused on phenotypic findings, endocrine changes, and genetic variation. We present a 14-year overview of a patient, from birth to skeletal maturity, with acroscyphodysplasia, noting the significant orthopaedic challenges and the need for a multidisciplinary team, including specialists in genetics, orthopaedics, endocrinology, and otolaryngology, to optimize long-term outcomes. CASE PRESENTATION: The patient presented as a newborn with dysmorphic facial features, including severe midface hypoplasia, malar flattening, nasal stenosis, and feeding difficulties. Radiologic findings were initially subtle, and a skeletal survey performed at age 7 months was initially considered normal. Genetic evaluation revealed a variant in PDE4D and subsequent pseudohypoparathyroidism. The patient presented to the department of orthopaedics, at age 2 years 9 months with a leg length discrepancy, right knee contracture, and severely crouched gait. Radiographs demonstrated cone-shaped epiphyses of the right distal femur and proximal tibia, but no evidence of growth plate changes in the left leg. The child developed early posterior epiphyseal arrest on the right side and required multiple surgical interventions to achieve neutral extension. Her left distal femur developed late posterior physeal arrest and secondary contracture without evidence of schypho deformity, which improved with anterior screw epiphysiodesis. The child required numerous orthopaedic surgical interventions to achieve full knee extension bilaterally. At age 13 years 11 months, she was an independent ambulator with erect posture. The child underwent numerous otolaryngology procedures and will require significant ongoing care. She has moderate intellectual disability. DISCUSSION AND CONCLUSIONS: Key challenges in the management of this case included the subtle changes on initial skeletal survey and the marked asymmetry of her deformity. While cone-shaped epiphyses are a hallmark of acrodysostosis, posterior tethering/growth arrest of the posterior distal femur has not been previously reported. Correction of the secondary knee contracture was essential to improve ambulation. Children with acroscyphodysplasia require a multidisciplinary approach, including radiology, genetics, orthopaedics, otolaryngology, and endocrinology specialties.

Fetal acute cerebral vasoreactivity to maternal hyperoxia in low-risk pregnancies: a cross-sectional study.

OBJECTIVE: To establish whether fetal cerebral vasoreactivity (CVRO2 ), following maternal hyperoxia, is predicted by fetal cerebral and uteroplacental Doppler pulsatility indices (PI) at baseline, fetal pulmonary vasoreactivity to oxygen (PVRO2 ), gestational age (GA), or sex. METHODS: Pulsatility index of middle (MCA), anterior (ACA), posterior cerebral (PCA), umbilical (UA), uterine (UtA), and branch of the pulmonary arteries (PA) were obtained, by ultrasound, before (baseline), during (hyperoxia) and after 15 minutes of maternal administration of 8 L/min of 100% oxygen, through a non-rebreathing face mask, in normal singleton pregnancies within 20 to 38 weeks' gestation. CVRO2 was defined as changes greater than zero in z score of PI of the cerebral arteries from baseline to hyperoxia. Logistic modeling was applied to identify CVRO2 predictors. RESULTS: A total of 97 pregnancies were eligible. In the overall population, median z scores of PI of MCA, ACA, and PCA did not differ between study phases. Based on the logistic model, baseline z scores for cerebral PI and GA were the best predictors of CVRO2 . CONCLUSIONS: In low-risk pregnancies, fetal CVRO2 to hyperoxia does not occur uniformly but depends on cerebral PI and GA at baseline. These findings may provide useful reference points when oxygen is administered in high-risk pregnancies.

The key role of the pediatric radiologist in developing a multidisciplinary fetal center.

With the demand for fetal imaging and fetal care programs on the rise, the authors of this manuscript review the components of building a successful fetal imaging center. Creating an environment that engages a multidisciplinary team, utilizing a central coordinator to review clinical and psychosocial aspects of each patient, and ensuring ongoing research and quality control are essential components to the success of growing a program.

Normal size of the fetal adrenal gland on prenatal magnetic resonance imaging.

BACKGROUND: The adrenal gland plays a vital role in fetal growth. Many disease states such as congenital adrenal hyperplasia, hemorrhage and tumors can lead to morphological changes in the gland. Ultrasound measurements of normal adrenal sizes in the fetus reported in the literature have shown a trend of increasing size with gestational age. There is no literature available on standard fetal adrenal sizes or detailed appearance by fetal MRI. OBJECTIVE: The purpose of this study was to provide MR data on the size and signal characteristics of the fetal adrenal gland throughout the second and third trimesters. MATERIALS AND METHODS: In this retrospective review, we selected 185 prenatal MRIs obtained from Jan. 1, 2014, to May 31, 2017, with normal abdominal findings for inclusion. The adrenal glands were identified in coronal, sagittal or axial T2-W planes and coronal T1-W plane when available. We measured the length and thickness of the medial and lateral limbs of the right and left adrenal glands and recorded signal intensity on T1-W and T2-W sequences, gender and gestational age in each case. RESULTS: The gestational age (GA) ranged 18-37 weeks. Visibility of the adrenal glands on T2-W images was high (90.3-97.2%) up to 30 weeks of GA but declined afterward (47.5-62.2% at 31-37 weeks). Visibility on T1-W images increased with GA, ranging from 21.4% visibility at 18-22 weeks and increasing to 40% at 35-37 weeks. Mean lengths of the adrenal gland limbs steadily increased from 8.2 mm at 18-22 weeks to 11.0 mm at 35-37 weeks. In the second trimester, adrenal glands were low in signal intensity on T2-W images and were surrounded by hyperintense perirenal fatty tissue. In the third trimester, the glands became less distinct, with increasing signal and obliteration of perirenal tissue. The glands were moderately hyperintense on T1-W images throughout pregnancy, with increasing visibility as pregnancy progressed. CONCLUSION: Normal sizes and signal intensities for adrenal glands are reported. Visibility of adrenal glands on T2-W images was 90.3-97.2% up to 30 weeks but declined thereafter. Visibility on T1-W images increased in the third trimester. Adrenal gland sizes increased with gestational age.

Coordination of the Fetal Medicine Institute and the Cleft and Craniofacial Center: Application to Early Management of Infants With Cleft Lip and Palate.

BACKGROUND/PURPOSE: The primary objective of this study is to describe the authors' experience at the Children's National Health System with the coordination of the Fetal Medicine Institute and the Cleft and Craniofacial Center. This collaboration highlights the accuracy and completeness of prenatal diagnosis of cleft abnormalities with expedient postnatal management. METHODS: With Institutional Review Board approval, the authors retrospectively reviewed 74 patients referred for potential orofacial cleft and 44 met the inclusion criteria. Follow-up fetal ultrasonography is typically performed and three-dimensional imaging was performed when feasible. If questionable anomalies or facial findings are present on these studies, the authors proceed with fetal magnetic resonance imaging. A thorough consultation is held with the cleft team, resulting in a comprehensive plan of care. Postnatal examination confirmed the correct prenatal diagnosis in nearly all patients. RESULTS: Sensitivity and specificity for isolated unilateral cleft lip were 89% and 100%, respectively; for unilateral cleft lip and palate, sensitivity and specificity were 82% and 90%, respectively; for bilateral cleft lip and palate, sensitivity and specificity were 97% and 90%, respectively. Initial postnatal evaluation by the cleft surgeon occurred at an average age of 21 days after birth. All patients who were candidates for presurgical orthodontia were treated at an appropriate young age (mean: 66.5 days). CONCLUSIONS: Coordinated prenatal evaluation of patients with cleft lip/palate by multidisciplinary centers plays an important role in the care of these complex patients. The results of the authors' study demonstrated high sensitivity and specificity for the prenatal diagnosis of cleft lip/palate, leading to timely postnatal evaluation and treatment.

Team counseling in prenatal evaluation: the partnership of the radiologist and genetic counselor.

Fetal medicine programs within children's hospitals have been developed to ensure access to pediatric specialists across multiple disciplines. The cases that present to these programs are usually complex and require involvement of a multidisciplinary care team. Although some providers on the team limit their focus to their pediatric specialty when counseling patients, the radiologist and genetic counselor have a distinct perspective allowing them to take the larger picture into account in the evaluation of the fetus. As first responders, they come together to review images and identify which consultants are most appropriate to counsel the families, and they can help guide patient discussions. In this paper we demonstrate how the combined expertise of the genetic counselor and pediatric radiologist can facilitate more accurate diagnoses and guide the appropriate management of complex fetal anomalies.

Imaging of congenital central nervous system infections.

Congenital central nervous system (CNS) infections are a cause of significant morbidity and mortality. The recent Zika virus outbreak raised awareness of congenital CNS infections. Imaging can be effective in diagnosing the presence and severity of infection. In this paper we review the clinical presentations and imaging characteristics of several common and less common congenital CNS infections.

Severe nasomaxillary hypoplasia (Binder phenotype) on prenatal US/MRI: an important marker for the prenatal diagnosis of chondrodysplasia punctata.

BACKGROUND: Chondrodysplasia punctata is a skeletal dysplasia caused by a diverse spectrum of etiologies, with outcomes ranging from antenatal demise to a normal life span. Prenatal detection can be challenging. OBJECTIVE: To review a series of cases of chondrodysplasia punctata associated with nasomaxillary hypoplasia, known as the Binder phenotype, and to highlight prenatal ultrasound and MRI findings, as well as postnatal MRI and radiographic findings. MATERIALS AND METHODS: We retrospectively reviewed ultrasound, MRI and radiographic imaging findings in postnatally confirmed cases of chondrodysplasia punctata from 2001 to 2017. We analyzed prenatal findings and correlated them with maternal history, postnatal imaging, phenotype, genetics and outcome. RESULTS: We identified eight cases, all with prenatal US and six of eight with prenatal MRI between 18 weeks and 32 weeks of gestational age. Reasons for referral included midface hypoplasia in four cases; family history in one case; intrauterine growth restriction in one case; short long-bones, intrauterine growth restriction and multicystic kidney in one case; and multiple anomalies in one case. In six cases, postnatal radiographs were performed. In four cases, postnatal spine MRI imaging was performed. The diagnosis of chondrodysplasia punctata was suggested in prenatal reports in six of eight fetuses. Seven of eight fetuses had Binder phenotype with severe nasomaxillary hypoplasia. Limb length was mildly symmetrically short in four of eight cases and normal in four of eight fetuses. Two of eight fetuses had epiphyseal stippling identified prenatally by US; this was present postnatally in six neonates on radiographs. Hand and foot abnormalities of brachytelephalangy were not detected on the prenatal US or MRI but were present in six of eigth fetuses on postnatal radiographs or physical exam. Four of eight fetuses had prenatal spine irregularity on US from subtle stippling. Six of eight had spine stippling on postnatal radiographs. One fetus had cervicothoracic kyphosis on prenatal US and MRI, and this was postnatally present in one additional neonate. One case had prenatally suspected C1 spinal stenosis with possible cord compression, and this was confirmed postnatally by MRI. There was a maternal history of systemic lupus erythematosus in two and hyperemesis gravidarum in one. Outcomes included one termination and seven survivors. CONCLUSION: Chondrodysplasia punctata can be identified prenatally but findings are often subtle. The diagnosis should be considered when a fetus presents with a hypoplastic midface known as the Binder phenotype. Maternal history of lupus, or other autoimmune diseases or hyperemesis gravidarum can help support the diagnosis.

Fetal intracranial hemorrhage: role of fetal MRI.

OBJECTIVE: To date, prenatal diagnosis of intracranial hemorrhage (ICH) is mainly based on ultrasound (US) findings rather than magnetic resonance imaging (MRI). We aimed to investigate the role of MRI in the diagnosis of fetal ICH among pregnancies referred to fetal MRI and to characterize the topography of fetal ICH using MRI. METHODS: We retrospectively identified fetal ICH cases diagnosed by MRI from 2008 to 2015 and reviewed their prenatal and postnatal medical records. RESULTS: Of the 2638 MRIs performed during the study period, 36 had ICH (median age 27 weeks). The most common US indication for MRI was a suspected cerebral anomaly (86%): 20 (55%) fetuses were referred for ventriculomegaly, 8 (22%) for ICH, and the other 8 had a variety of different indications. We distinguished two broad topographic patterns: (1) those related to hemorrhage of the periventricular germinal matrix (GMH, n = 24; 67%) and (2) those not related to GMH (non-GMH, n = 12; 33%). GMH fetuses were referred to MRI later (median 28 vs 22 weeks, p = 0.005). Intrauterine demise was more frequent in non-GMH (58% vs 4%, p < 0.001). CONCLUSION: Magnetic resonance imaging is an important tool in prenatal diagnosis of ICH, especially when US describes nonspecific intracranial abnormalities. GMH occurs more frequently and later in pregnancy than non-GMH. © 2017 John Wiley & Sons, Ltd.

Prenatal congenital vertical talus (rocker bottom foot): a marker for multisystem anomalies.

BACKGROUND: Congenital vertical talus is a rare foot anomaly characterized by a prominent calcaneus and rigid forefoot dorsiflexion. While congenital vertical talus has been associated with anomalies such as trisomy 18, myelomeningocele and arthrogryposis, postnatal series have reported cases of isolated congenital vertical talus. OBJECTIVE: The purpose of our study was to determine the incidence of isolated congenital vertical talus prenatally and identify the most common anomalies associated with this finding. MATERIALS AND METHODS: A retrospective review was performed of congenital vertical talus cases identified in our fetal center from 2006 to 2015. The prenatal US and MR imaging appearance of congenital vertical talus was evaluated and differentiation from congenital talipes equinovarus was assessed. Studies were evaluated for additional abnormalities affecting the central nervous system, face, limbs, viscera, growth and amniotic fluid. Imaging findings were recorded and correlated with outcomes when available. RESULTS: Twenty-four cases of congenital vertical talus were identified prenatally (gestational age: 19-36 weeks). All 24 had prenatal US and 21 also underwent fetal MRI on the same day. There were no isolated cases of congenital vertical talus in this series; all 24 had additional anomalies identified prenatally. Sixteen cases had bilateral congenital vertical talus (67%). Additional anomalies were identified in the brain (15), spine (11), face (6), abdominal wall (3), heart (8) and other limbs (12). Chromosomal abnormalities were identified in 6 of 20 patients who underwent genetic testing. Overall, US held some advantage in detecting the abnormality: in 10 cases, US depicted congenital vertical talus more clearly than MRI; in 8 cases, US and MRI were equal in detection and in 3 cases, MRI was superior. In 9/15 cases with intracranial abnormalities, MRI was superior to US in demonstrating structural anomalies. Outcomes included termination (11), intrauterine fetal demise (1), stillbirth or immediate neonatal demise (5), lost to follow-up (1), and 6 survivors with postnatal follow-up. CONCLUSION: In our series, there were no cases of isolated congenital vertical talus, with additional anomalies variably affecting multiple systems including the brain, spine, face, viscera and limbs. When congenital vertical talus is identified prenatally, a thorough search for additional anomalies is indicated. Fetal MRI can be a useful adjunct in confirming the diagnosis and further delineating additional anomalies, particularly in the brain and spine.

Prenatal magnetic resonance and ultrasonographic findings in small-bowel obstruction: imaging clues and postnatal outcomes.

BACKGROUND: Prenatal small-bowel obstruction can result from single or multiple atresias, and it can be an isolated abnormality or part of a syndrome. It is sometimes the first manifestation of cystic fibrosis. Accurate prediction of the level of obstruction and length of bowel affected can be difficult, presenting a challenge for counseling families and planning perinatal management. OBJECTIVE: To review the prenatal US and MRI findings of small-bowel obstruction and to assess whether fetal MRI adds information that could improve prenatal counseling and perinatal management. MATERIALS AND METHODS: We retrospectively reviewed 12 prenatally diagnosed cases of small-bowel obstruction evaluated by both US and MRI from 2005 to 2015. We analyzed gestational age at evaluation, US and MRI findings, gestational age at delivery and postnatal outcomes. RESULTS: The final diagnoses were jejunal atresia (7), ileal atresia (1), cystic fibrosis (3) and combined jejunal and anal atresia (1). Four of the eight with jejunal atresia were found to have multiple small-bowel atresias. Prenatal perforation was noted in three. We identified a trend of increasing complexity of bowel contents corresponding to progressively distal level of obstruction, as indicated by increasing US echogenicity and high T1 signal on MRI. Seven cases of jejunal atresia and one case of ileal atresia demonstrated small ascending, transverse and descending colon (microcolon) with filling of a normal-diameter rectum. In contrast, all three fetuses with cystic fibrosis and the fetus with jejunal-anal atresia demonstrated microcolon as well as abnormal paucity or absence of rectal meconium. Polyhydramnios was present in nine. Eight were delivered prematurely, of whom seven had polyhydramnios. The fetus with jejunal and anal atresia died in utero. Postnatally, three had short gut syndrome, all resulting from multiple jejunal atresias; these three were among a subset of four fetuses whose bowel diameter measured more than 3 cm. Eight infants had no further gastrointestinal complications. The presence of multiple atresias was not predicted by prenatal US or MRI. CONCLUSION: MR provides useful additional information regarding meconium distribution in the small bowel, which helps to clarify the level of obstruction. MR was additionally useful in the assessment of colon and rectal contents, serving as a fetal enema. Abnormally diminished meconium in the rectum suggests cystic fibrosis or combined small-bowel and colonic obstruction, information that is useful in counseling and preparing for postnatal care.

Ultrasound and MR imaging findings in prenatal diagnosis of craniosynostosis syndromes.

BACKGROUND: Craniosynostosis syndromes are uncommonly encountered in the prenatal period. Identification is challenging but important for family counseling and perinatal management. OBJECTIVE: This series examines prenatal findings in craniosynostosis syndromes, comparing the complementary roles of US and MRI and emphasizing clues easily missed in the second trimester. MATERIALS AND METHODS: Six prenatal cases evaluated from 2002 through 2011 were retrospectively reviewed. Referral history, gestational age, and sonographic and MRI findings were reviewed by three pediatric radiologists. Abnormalities of the calvarium, hands, feet, face, airway and central nervous system were compared between modalities. RESULTS: The diagnosis was Apert syndrome in three, Pfeiffer syndrome in two and Carpenter syndrome in one. The gestational age at evaluation ranged from 21 to 33 weeks. All six were evaluated by MRI and US, with two undergoing repeat evaluation in the third trimester, yielding a total of eight MRIs and US exams. The referral history suggested cloverleaf skull in two cases but did not suggest craniosynostosis syndrome in any case. In four, the referral suggested central nervous system (CNS) findings that were not confirmed by MRI; additional CNS findings were discovered in the remaining two. In four cases, developing turricephaly resulted in a characteristic "lampshade" contour of the fetal head. Hypertelorism and proptosis were present in five, with proptosis better appreciated by MRI. Digit abnormalities were present in all, seen equally well by MRI and US. Lung abnormalities in the second trimester in one fetus resolved by the third trimester. CONCLUSION: Prenatal diagnosis of craniosynostosis syndromes is difficult prior to the third trimester. MRI and US have complementary roles in evaluation of these patients.

Prenatal counseling tools for the pediatric radiologist as part of a multidisciplinary team.

Fetal abnormalities are present in 3-5% of all pregnancies, leading to increased anxiety and the need for important discussions between patients and their care providers. Regardless of the severity of the anomaly, receiving the information can be traumatic for the pregnant patient and her partner. Most physicians who aren't trained to provide prenatal counseling understandably feel uncomfortable with the uncertainty and complex issues that arise in such high-stress counseling sessions. Genetic counselors are specifically trained to counsel patients in the setting of a fetal abnormality; however additional input from pediatric radiologists and other pediatric specialists is invaluable to parents in these situations and such input is an essential part of a team approach to prenatal counseling. The goal of this article is to provide a basic approach to counseling in the prenatal setting for pediatric radiologists and other specialists.

Prenatal evaluation of atelencephaly.

Atelencephaly is a rare lethal congenital brain malformation characterized by underdevelopment of the prosencephalon and is often accompanied by the facial features seen in some cases of holoprosencephaly, such as cyclopia. We report a case of atelencephaly in the fetus with characteristic ultrasound findings. In addition, we report the findings on fetal MRI, which have not been previously described in the literature.

Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta.

A recessive form of severe osteogenesis imperfecta that is not caused by mutations in type I collagen has long been suspected. Mutations in human CRTAP (cartilage-associated protein) causing recessive bone disease have been reported. CRTAP forms a complex with cyclophilin B and prolyl 3-hydroxylase 1, which is encoded by LEPRE1 and hydroxylates one residue in type I collagen, alpha1(I)Pro986. We present the first five cases of a new recessive bone disorder resulting from null LEPRE1 alleles; its phenotype overlaps with lethal/severe osteogenesis imperfecta but has distinctive features. Furthermore, a mutant allele from West Africa, also found in African Americans, occurs in four of five cases. All proband LEPRE1 mutations led to premature termination codons and minimal mRNA and protein. Proband collagen had minimal 3-hydroxylation of alpha1(I)Pro986 but excess lysyl hydroxylation and glycosylation along the collagen helix. Proband collagen secretion was moderately delayed, but total collagen secretion was increased. Prolyl 3-hydroxylase 1 is therefore crucial for bone development and collagen helix formation.

Fallopian tube torsion in the pediatric age group: radiologic evaluation.

Fallopian tube torsion is a rare but important cause of acute pelvic pain in young adolescent girls. It is a surgical emergency treated with either detorsion or salpingectomy. The imaging findings can be nonspecific and challenging. However, an accurate early diagnosis is essential for prompt surgical treatment. Our objective was to review whether imaging findings can be specific enough to suggest the diagnosis of tubal torsion prospectively in the appropriate clinical setting. An Institutional Review Board-approved retrospective review of our imaging database from 2005 to 2012 revealed 10 surgically proven cases of fallopian tube torsion. All cases had sonography performed; 5 cases had additional multidetector computed tomography. All 10 patients (9-17 years) presented with acute pelvic pain. Sonographic findings included dilated tubular structures in 6 of 10 cases: adjacent to a normal ipsilateral ovary in 5 of 6 and adjacent to a benign ovarian teratoma in 1. In 4 cases, no dilated tube was identified; 3 of 4 had a cystic mass separate from the ovaries, and 1 had the imaging appearance of a multicystic ovary. Computed tomographic findings in the 5 cases that underwent multidetector computed tomography included a dilated tubular structure in 3 of 5; 2 of 5 had a cystic adnexal mass identified. Although rare, tubal torsion should be considered in female adolescents with acute pelvic pain. Sonography should be the first imaging choice. When a tubular structure or a midline cystic mass associated with a normal ipsilateral ovary is noted, tubal torsion should be considered in the differential diagnosis.

Neurodevelopmental Outcomes of Normocephalic Colombian Children with Antenatal Zika Virus Exposure at School Entry.

The long-term neurodevelopmental effects of antenatal Zika virus (ZIKV) exposure in children without congenital Zika syndrome (CZS) remain unclear, as few children have been examined to the age of school entry level. A total of 51 Colombian children with antenatal ZIKV exposure without CZS and 70 unexposed controls were evaluated at 4-5 years of age using the Behavior Rating Inventory of Executive Function (BRIEF), the Pediatric Evaluation of Disability Inventory (PEDI-CAT), the Bracken School Readiness Assessment (BSRA), and the Movement Assessment Battery for Children (MABC). The mean ages at evaluation were 5.3 and 5.2 years for cases and controls, respectively. Elevated BRIEF scores in Shift and Emotional Control may suggest lower emotional regulation in cases. A greater number of cases were reported by parents to have behavior and mood problems. BSRA and PEDI-CAT activity scores were unexpectedly higher in cases, most likely related to the COVID-19 pandemic and a delayed school entry among the controls. Although PEDI-CAT mobility scores were lower in cases, there were no differences in motor scores on the MABC. Of 40 cases with neonatal neuroimaging, neurodevelopment in 17 with mild non-specific findings was no different from 23 cases with normal neuroimaging. Normocephalic children with ZIKV exposure have positive developmental trajectories at 4-5 years of age but differ from controls in measures of emotional regulation and adaptive mobility, necessitating continued follow-up.