The utility of the fronto-temporal horn ratio on cranial ultrasound in premature newborns: a ventriculomegaly marker.

BACKGROUND: The aims of this study were to find the normal value of fronto-temporal horn ratio (FTHR) as a marker of ventriculomegaly on cranial ultrasound (CUS) in premature newborns and the relation to white matter injury (WMI) and cerebral palsy (CP). METHODS: This is a retrospective study of newborns admitted between 2011 and 2014. Inclusion criteria were: (1) gestation <29 weeks, (2) birth weight ≤1500 g, (3) referred within 7 days of life, (4) at least two CUS preformed, (5) brain magnetic resonance imaging (MRI) at term age-equivalent. Intraventricular hemorrhage (IVH) grade was identified and FTHR was measured on all CUS. WMI on MRI was evaluated through (1) injury score (Kidokoro 2013) and (2) fractional anisotropy (FA) on the MRI diffusion tensor imaging. CP was estimated using the gross motor function classification system (GMFCS). RESULTS: One hundred neonates met the inclusion criteria: 37 with no IVH, 36 with IVH grade 1-2, and 27 with IVH grade 3-4. The FTHR cut-point of 0.51 had the highest sensitivity and specificity for moderate-to-severe WMI. In the IVH grade 3-4 group, the elevated FTHR correlated with lower FA and higher GMFCS. CONCLUSIONS: FTHR is a useful quantitative biomarker of ventriculomegaly in preterm newborns. It may help standardize ventricular measurement and direct intervention. IMPACT: The fronto-temporal horn ratio has the potential to become a standardized tool that can provide an actionable measure to direct intervention for post-hemorrhagic ventricular dilation. This current study will provide the basis of a future clinical trial to optimize intervention timing to decrease the risk of white matter injury in this vulnerable population.

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.

Risk Factors for Brain Injury in Newborns Treated with Extracorporeal Membrane Oxygenation.

OBJECTIVE: This study aimed to assess the association of clinical risk factors with severity of magnetic resonance imaging (MRI) brain injury in neonatal extracorporeal membrane oxygenation (ECMO) patients. STUDY DESIGN: This is a single-center retrospective study conducted at an outborn level IV neonatal intensive care unit in a free-standing academic children's hospital. Clinical and MRI data from neonates treated with ECMO between 2005 and 2015 were reviewed. MRI injury was graded by two radiologists according to a modified scoring system that assesses parenchymal injury, extra-axial hemorrhage, and cerebrospinal fluid spaces. MRI severity was classified as none (score = 0), mild/moderate (score = 1-13.5), and severe (score ≥ 14). The relationship between selected risk factors and MRI severity was assessed by Chi-square, analysis of variance, and Kruskal-Wallis tests where appropriate. Combinative predictive ability of significant risk factors was assessed by logistic regression analyses. RESULTS: MRI data were assessed in 81 neonates treated with ECMO. Veno-arterial (VA) patients had more severe injury compared with veno-venous patients. There was a trend toward less severe injury over time. After controlling for covariates, duration of ECMO remained significantly associated with brain injury, and the risk for severe injury was significantly increased in patients on ECMO beyond 210 hours. CONCLUSION: Risk for brain injury is increased with VA ECMO and with longer duration of ECMO. Improvements in care may be leading to decreasing incidence of brain injury in neonatal ECMO patients. KEY POINTS: · Veno-arterial ECMO is associated with more brain injury by MRI compared with veno-venous ECMO.. · Longer duration of ECMO is significantly associated with severe brain injury by MRI.. · Risk for neurologic injury may be decreasing over time with advances in neonatal ECMO..

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.

Variability in antenatal prognostication of fetal diaphragmatic hernia across the North American Fetal Therapy Network (NAFTNet).

OBJECTIVE: To evaluate variability in antenatal sonographic prognostication of congenital diaphragmatic hernia (CDH) within the North American Fetal Therapy Network (NAFTNet). METHODS: NAFTNet centre were invited to complete a questionnaire and participate in videoconference calls, during which participants were observed while measuring lung area by ultrasound using the anteroposterior (AP) method, longest method, and trace method. Each center identified 1-2 experienced fetal medicine specialist(s) or medical imaging specialists locally to participate in the study. Practices were compared among NAFTNet centre within and without the fetal endoscopic tracheal occlusion (FETO) consortium. RESULTS: Nineteen participants from 9 FETO center and 30 participants from 17 non-FETO center completed the survey and 31 participants were interviewed and observed while measuring sonographic lung area. All Centres measured observed-to-expected lung-to-head ratio (o/e LHR) or LHR for CDH prognostication. Image selection criteria for lung area measurement were consistent, including an axial section of the chest with clear lung borders and a 4-chamber cardiac view. Lung area measurement methods varied across NAFTNet, with most centre using longest (4/9 FETO vs. 13/29 non-FETO) or trace (3/9 FETO vs. 11/29 non-FETO) method. Centres differed in expected reference ranges for o/e LHR determination and whether the lowest, highest or average o/e LHR was utilized. CONCLUSION: Variability in antenatal sonographic prognostication of CDH was identified across NAFTNet, indicating a need for consensus-based standardization.

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.

Techniques for minimizing sedation in pediatric MRI.

MRI is used widely in infants and young children. However, in these young cases deep sedation or general anesthesia is often required to minimize motion artifacts during MRI examinations. Although the benefits of MR typically outweigh the potential risks of sedation when delivered by an experienced team, there are increasing concerns regarding the affect of sedation on young children. There continues to be a push to develop various strategies that can minimize the need for sedation. The present review summarizes several technical and clinical approaches that can help decrease the need for sedation in the pediatric patient. Optimization of the MRI environment, the role of child life specialists, feed-and-bundle and distraction techniques, noise-reduction methods, artificial intelligence, and MRI advances to decrease both scan times and motion artifacts will be discussed. Level of Evidence: 5 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019.

In vivo textural and morphometric analysis of placental development in healthy & growth-restricted pregnancies using magnetic resonance imaging.

BACKGROUND: The objective of this study was to characterize structural changes in the healthy in vivo placenta by applying morphometric and textural analysis using magnetic resonance imaging (MRI), and to explore features that may be able to distinguish placental insufficiency in fetal growth restriction (FGR). METHODS: Women with healthy pregnancies or pregnancies complicated by FGR underwent MRI between 20 and 40 weeks gestation. Measures of placental morphometry (volume, elongation, depth) and digital texture (voxel-wise geometric and signal-intensity analysis) were calculated from T2W MR images. RESULTS: We studied 66 pregnant women (32 healthy controls, 34 FGR); during the study period, placentas undergo significant increases in size; signal intensity remains relatively constant, however there is increasing variation in spatial arrangements, suggestive of progressive microstructural heterogeneity. In FGR, placental size is smaller, with great homogeneity of signal intensity and spatial arrangements. CONCLUSION: We report quantitative textural and morphometric changes in the in vivo placenta in healthy controls over the second half of pregnancy. These MRI features demonstrate important differences in placental development in the setting of placental insufficiency that relate to onset and severity of FGR, as well as neonatal outcome.

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.

In vivo placental MRI shape and textural features predict fetal growth restriction and postnatal outcome.

PURPOSE: To investigate the ability of three-dimensional (3D) MRI placental shape and textural features to predict fetal growth restriction (FGR) and birth weight (BW) for both healthy and FGR fetuses. MATERIALS AND METHODS: We recruited two groups of pregnant volunteers between 18 and 39 weeks of gestation; 46 healthy subjects and 34 FGR. Both groups underwent fetal MR imaging on a 1.5 Tesla GE scanner using an eight-channel receiver coil. We acquired T2-weighted images on either the coronal or the axial plane to obtain MR volumes with a slice thickness of either 4 or 8 mm covering the full placenta. Placental shape features (volume, thickness, elongation) were combined with textural features; first order textural features (mean, variance, kurtosis, and skewness of placental gray levels), as well as, textural features computed on the gray level co-occurrence and run-length matrices characterizing placental homogeneity, symmetry, and coarseness. The features were used in two machine learning frameworks to predict FGR and BW. RESULTS: The proposed machine-learning based method using shape and textural features identified FGR pregnancies with 86% accuracy, 77% precision and 86% recall. BW estimations were 0.3 ± 13.4% (mean percentage error ± standard error) for healthy fetuses and -2.6 ± 15.9% for FGR. CONCLUSION: The proposed FGR identification and BW estimation methods using in utero placental shape and textural features computed on 3D MR images demonstrated high accuracy in our healthy and high-risk cohorts. Future studies to assess the evolution of each feature with regard to placental development are currently underway. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:449-458.

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.

X-linked hypomyelination with spondylometaphyseal dysplasia (H-SMD) associated with mutations in AIFM1.

An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, and recent genetic characterization in two families with a common AIFM1 mutation. In our study, 12 patients (6 families) with H-SMD were identified and underwent comprehensive assessment accompanied by whole-exome sequencing (WES). Pedigree analysis in all families was consistent with X-linked recessive inheritance. Presentation typically occurred between 12 and 36 months. In addition to the two disease-defining features of spondylometaphyseal dysplasia and hypomyelination on MRI, common clinical signs and symptoms included motor deterioration, spasticity, tremor, ataxia, dysarthria, cognitive defects, pulmonary hypertension, nystagmus, and vision loss due to retinopathy. The course of the disease was slowly progressive. All patients had maternally inherited or de novo mutations in or near exon 7 of AIFM1, within a region of 70 bp, including synonymous and intronic changes. AIFM1 mutations have previously been associated with neurologic presentations as varied as intellectual disability, hearing loss, neuropathy, and striatal necrosis, while AIFM1 mutations in this small region present with a distinct phenotype implicating bone. Analysis of cell lines derived from four patients identified significant reductions in AIFM1 mRNA and protein levels in osteoblasts. We hypothesize that AIFM1 functions in bone metabolism and myelination and is responsible for the unique phenotype in this condition.

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.