RESUMEN
We identify a population of Protogenin-positive (PRTG+ve) MYChigh NESTINlow stem cells in the four-week-old human embryonic hindbrain that subsequently localizes to the ventricular zone of the rhombic lip (RLVZ). Oncogenic transformation of early Prtg+ve rhombic lip stem cells initiates group 3 medulloblastoma (Gr3-MB)-like tumors. PRTG+ve stem cells grow adjacent to a human-specific interposed vascular plexus in the RLVZ, a phenotype that is recapitulated in Gr3-MB but not in other types of medulloblastoma. Co-culture of Gr3-MB with endothelial cells promotes tumor stem cell growth, with the endothelial cells adopting an immature phenotype. Targeting the PRTGhigh compartment of Gr3-MB in vivo using either the diphtheria toxin system or chimeric antigen receptor T cells constitutes effective therapy. Human Gr3-MBs likely arise from early embryonic RLVZ PRTG+ve stem cells inhabiting a specific perivascular niche. Targeting the PRTGhigh compartment and/or the perivascular niche represents an approach to treat children with Gr3-MB.
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Meduloblastoma , Células Madre Neoplásicas , Humanos , Meduloblastoma/patología , Meduloblastoma/metabolismo , Animales , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Ratones , Rombencéfalo/metabolismo , Rombencéfalo/embriología , Neoplasias Cerebelosas/metabolismo , Neoplasias Cerebelosas/patología , Células Endoteliales/metabolismo , Nicho de Células Madre , Células Madre/metabolismo , Técnicas de Cocultivo , Estructuras Embrionarias , Metencéfalo/embriologíaRESUMEN
Eosinophilic/T-cell chorionic vasculitis (ETCV) is an idiopathic lesion composed of eosinophils, CD3+ T lymphocytes, and histiocytes. In twins, ETCV may affect only one chorionic plate, a feature defined as "discordant". We present a case of ETCV discordance in a diamniotic dichorionic placenta at 38 weeks of gestation, in which the female twin was small for gestational age, weighing 2670 g (25th percentile). The corresponding placental territory presented ETCV in two close chorionic vessels with concordance of the fetal inflammatory response. Immunohistochemistry showed an abundance of CD3+/CD4+/CD25+T lymphocytes, CD68 PG M1+ macrophages, and scattered CD8+ T cells with focal TIA-1 positivity. Granzyme B, CD20 B lymphocytes, and CD56 natural killer cells were negative. High-grade villitis of unknown etiology (VUE) was additionally found and displayed comparable ETCV findings, except for an equivalent ratio of CD4+/CD8+ T cells, but TIA-1 was focally expressed. VUE was associated with chronic histiocytic intervillositis (CHI). The combination of ETCV, VUE, and CHI may have been responsible for reduced fetal growth. Concordance was observed in the ETCV and TIA-1 expression, both in ETCV and in VUE, which is a maternal response. These findings may suggest a common antigen or chemokine pathway to which both mother and fetus accordingly responded.
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Enfermedades Placentarias , Vasculitis , Femenino , Embarazo , Humanos , Placenta/metabolismo , Enfermedades Placentarias/metabolismo , Corion/metabolismo , Linfocitos T CD8-positivos , Vellosidades Coriónicas/metabolismoRESUMEN
Background: Walker-Warburg syndrome (WWS) (OMIM #236670) is an autosomal recessive disorder characterized by congenital muscular dystrophy, hydrocephalus, cobblestone lissencephaly, and retinal dysplasia. The main genes involved are: POMT1, POMT2, POMGNT1, FKTN, LARGE1, and FKRP. Case report: We present a fetus with WWS showing at ultrasound severe triventricular hydrocephalus. Pregnancy was legally terminated at 21 weeks +2 days of gestation. In vivo and postmortem magnetic resonance revealed corpus callosum agenesis and cerebellar hypoplasia. Cobblestone lissencephaly was observed at post-mortem. Next generation sequencing (NGS) of 193 genes, performed on fetal DNA extracted from amniocytes, detected two heterozygous mutations in the POMT2 gene. The c.1238G > C p.(Arg413Pro) mutation was paternally inherited and is known to be pathogenic. The c.553G > A p.(Gly185Arg) mutation was maternally inherited and has not been previously described. Conclusion: Compound heterozygous mutations in the POMT2 gene caused a severe cerebral fetal phenotype diagnosed prenatally at midgestation allowing therapeutic pregnancy termination.
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Lisencefalia de Cobblestone , Hidrocefalia , Síndrome de Walker-Warburg , Humanos , Femenino , Embarazo , Síndrome de Walker-Warburg/diagnóstico , Síndrome de Walker-Warburg/genética , Mutación Missense , Lisencefalia de Cobblestone/genética , Mutación , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/genética , Presentación en Trabajo de Parto , Pentosiltransferasa/genéticaRESUMEN
Dandy-Walker malformation (DWM) and Cerebellar vermis hypoplasia (CVH) are commonly recognized human cerebellar malformations diagnosed following ultrasound and antenatal or postnatal MRI. Specific radiological criteria are used to distinguish them, yet little is known about their differential developmental disease mechanisms. We acquired prenatal cases diagnosed as DWM and CVH and studied cerebellar morphobiometry followed by histological and immunohistochemical analyses. This was supplemented by laser capture microdissection and RNA-sequencing of the cerebellar rhombic lip, a transient progenitor zone, to assess the altered transcriptome of DWM vs control samples. Our radiological findings confirm that the cases studied fall within the accepted biometric range of DWM. Our histopathological analysis points to reduced foliation and inferior vermian hypoplasia as common features in all examined DWM cases. We also find that the rhombic lip, a dorsal stem cell zone that drives the growth and maintenance of the posterior vermis is specifically disrupted in DWM, with reduced proliferation and self-renewal of the progenitor pool, and altered vasculature, all confirmed by transcriptomics analysis. We propose a unified model for the developmental pathogenesis of DWM. We hypothesize that rhombic lip development is disrupted through either aberrant vascularization and/or direct insult which causes reduced proliferation and failed expansion of the rhombic lip progenitor pool leading to disproportionate hypoplasia and dysplasia of the inferior vermis. Timing of insult to the developing rhombic lip (before or after 14 PCW) dictates the extent of hypoplasia and distinguishes DWM from CVH.
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Cerebelo/anomalías , Síndrome de Dandy-Walker/embriología , Síndrome de Dandy-Walker/patología , Desarrollo Fetal/fisiología , Feto/patología , Malformaciones del Sistema Nervioso/embriología , Malformaciones del Sistema Nervioso/patología , Estudios de Casos y Controles , Cerebelo/embriología , Cerebelo/patología , Discapacidades del Desarrollo/patología , Humanos , Recién NacidoRESUMEN
PURPOSE: The aims of this study were to characterize isolated and non-isolated forms of corpus callosum dysgenesis (CCD) at fetal magnetic resonance imaging (MRI) and to identify early predictors of associated anomalies. METHODS: We retrospectively analyzed 104 fetuses with CCD undergoing MRI between 2006 and 2016. Corpus callosum, cavum septi pellucidi, biometry, presence of ventriculomegaly, gyration anomalies, cranio-encephalic abnormalities and body malformations were evaluated. Results of genetic tests were also recorded. RESULTS: At MRI, isolated CCD was 26.9%, the rest being associated to other abnormalities. In the isolated group, median gestational age at MRI was lower in complete agenesis than in hypoplasia (22 vs 28 weeks). In the group with additional findings, cortical dysplasia was the most frequently associated feature (P = 0.008), with a more frequent occurrence in complete agenesis (70%) versus other forms; mesial frontal lobes were more often involved than other cortical regions (P = 0.006), with polymicrogyria as the most frequent cortical malformation (40%). Multivariate analysis confirmed the association between complete agenesis and cortical dysplasia (odds ratio = 7.29, 95% confidence interval 1.51-35.21). CONCLUSIONS: CCD is often complicated by other intra-cranial and extra-cranial findings (cortical dysplasias as the most prevalent) that significantly affect the postnatal prognosis. The present study showed CCD with associated anomalies as more frequent than isolated (73.1%). In isolated forms, severe ventriculomegaly was a reliable herald of future appearance of associated features. © 2016 John Wiley & Sons, Ltd.
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Anomalías Múltiples/diagnóstico , Agenesia del Cuerpo Calloso/diagnóstico , Imagen por Resonancia Magnética , Diagnóstico Prenatal/métodos , Anomalías Múltiples/epidemiología , Adulto , Agenesia del Cuerpo Calloso/epidemiología , Estudios Transversales , Femenino , Edad Gestacional , Humanos , Masculino , Embarazo , Pronóstico , Estudios RetrospectivosRESUMEN
Autosomal aneuploidies associate with multiple minor skeletal defects, which, in fetuses, are best appreciated post-mortem after specific anatomic preparations. The present study was aimed to define patterns of skeletal anomalies in autosomal aneuploidies at standard radiology in second trimester fetuses by comparing findings in and among genotypes and gestational ages. Aneuploid fetuses were selected for availability of radiographs of various axial and non-axial structures, mainly homeotic transformations, vertebral clefts, vertebral segmentation and ossification defects, absent/hypoplastic nasal bone, premature talar calcifications, and selected appendicular anomalies. Eighty six fetuses with trisomy 21, 39 with trisomy 18, eight with trisomy 13, six with triploidy, and six with rare autosomal aneuploidies were identified, 75.2% showing an abnormal costo-vertebral pattern, mostly cervical ribs, absence of the 12th thoracic ribs and posterior homeotic change. Clefting was observed along the entire spine, especially sagittal lumbar clefts, and coronal thoracic clefts. Four different types of vertebral clefting were identified, including type 1 (butterfly), type 2 (incomplete inferior), type 3 (incomplete superior), and type 4 (complete). Attenuation of clefting by gestational age was observed in trisomy 21 and 18. These findings define more clearly the pattern of perturbed morphogenesis in aneuploidy as a type of amplified developmental instability with pleiotropic effects on skeletogenesis.
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Aneuploidia , Huesos/anomalías , Trastornos de los Cromosomas/diagnóstico , Síndrome de Down/diagnóstico , Trisomía/diagnóstico , Aborto Eugénico , Autopsia , Huesos/diagnóstico por imagen , Huesos/metabolismo , Trastornos de los Cromosomas/diagnóstico por imagen , Trastornos de los Cromosomas/genética , Trastornos de los Cromosomas/patología , Cromosomas Humanos Par 13/genética , Cromosomas Humanos Par 18/genética , Síndrome de Down/diagnóstico por imagen , Síndrome de Down/genética , Síndrome de Down/patología , Femenino , Feto , Edad Gestacional , Humanos , Masculino , Osteogénesis/genética , Embarazo , Segundo Trimestre del Embarazo , Diagnóstico Prenatal , Estudios Retrospectivos , Trisomía/genética , Trisomía/patología , Síndrome de la Trisomía 13 , Síndrome de la Trisomía 18RESUMEN
BACKGROUND: Oropharyngeal teratoma may occur by itself or together with other craniofacial malformations, most commonly cleft palate. Oropharyngeal teratoma may be also seen in association with frontonasal dysplasia and/or various degrees of craniofacial duplication. The nosology of these sporadic disorders is poorly defined. CASE AND REVIEW: We report on a 22-week fetus with a protruding nasopharyngeal teratoma, partial oral duplication, anencephaly, multiple costo-vertebral segmentation defects, and cervical diplomyelia. A review of the literature identified 48 patients published from 1931 to 2013 with co-existing clefting and duplication anomalies of the cephalic pole. Thoracic and abdominal midline anomalies were reported 13 times. CONCLUSION: The term "craniofacial teratoma syndrome" is introduced to define this phenotype as a recognizable developmental field defect of the cephalic pole. Developmental pathogenesis is discussed with a focus on pleiotropy and stereotaxis. The observation of midline findings suggestive of holoprosencephaly in a few previously reported cases suggests a role for the sonic hedgehog signaling pathway in this malformation pattern.
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Anomalías Múltiples/patología , Anencefalia/patología , Vértebras Cervicales/anomalías , Feto/patología , Anomalías de la Boca/patología , Neoplasias Orofaríngeas/patología , Teratoma/patología , Humanos , Síndrome , Terminología como AsuntoRESUMEN
OBJECTIVE: The study aims to demonstrate the value of the 'tail sign' in the assessment of Dandy-Walker malformation. METHODS: A total of 31 fetal magnetic resonance imaging (MRI), performed before 24 weeks of gestation after second-line ultrasound examination between May 2013 and September 2014, were examined retrospectively. All MRI examinations were performed using a 1.5 Tesla magnet without maternal sedation. RESULTS: Magnetic resonance imaging diagnosed 15/31 cases of Dandy-Walker malformation, 6/31 of vermian partial caudal agenesis, 2/31 of vermian hypoplasia, 4/31 of vermian malrotation, 2/31 of Walker-Warburg syndrome, 1/31 of Blake pouch cyst and 1/31 of rhombencephalosynapsis. All data were compared with fetopsy results, fetal MRI after the 30th week or postnatal MRI; the follow-up depended on the maternal decision to terminate or continue pregnancy. In our review study, we found the presence of the 'tail sign'; this sign was visible only in Dandy-Walker malformation and Walker-Warburg syndrome. CONCLUSION: The 'tail sign' could be helpful in the difficult differential diagnosis between Dandy-Walker, vermian malrotation, vermian hypoplasia and vermian partial agenesis.
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Síndrome de Dandy-Walker/diagnóstico , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética , Embarazo , Diagnóstico Prenatal , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: The purpose of this study is to define the role of foetal magnetic resonance imaging (MRI) in evaluating cerebral ischaemic-haemorrhagic lesions and the extension of parenchymal injuries. STUDY DESIGN: From September 2006 to September 2010, 271 foetal MRI have been performed on cases referred to us for ultrasound suspect of brain abnormalities or cytomegalovirus infection and Toxoplasma serum conversion. Foetal MRI was performed with a 1.5-T magnet system without mother sedation. RESULTS: Foetal MRI detected ischaemic-haemorrhagic lesions in 14 of 271 foetuses, consisting of 5% incidence. MRI confirmed the diagnosis in three of 14 cases with ultrasonography (US) suspect of ischaemic-haemorrhagic lesions associated with ventriculomegaly. In one of 14 cases with US findings of cerebellar haemorrhage, MRI confirmed the diagnosis and provided additional information regarding the parenchymal ischaemic injury. In eight of 14 cases with US suspect of ventriculomegaly (3), corpus callosum agenesis (2), hypoplasia of cerebellar vermis (1), holoprosencephaly (1) and spina bifida (1), MRI detected ischaemic and haemorrhagic lesions unidentified at US examination. In two of 14 foetuses with US suspect of intracerebral space-occupying lesion, MRI modified the diagnosis to extra-axial haematoma associated with dural sinus malformation. Results were compared with post-mortem findings or afterbirth imaging follow-up. CONCLUSIONS: Foetal MRI is an additional imaging modality in the diagnosis of cerebral ischemic-haemorrhagic lesions, and it is useful in providing further information on the extension of the parenchymal injury and associated abnormalities, thus improving delivery management.
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Isquemia Encefálica/embriología , Hemorragia Cerebral/embriología , Enfermedades Fetales/diagnóstico , Imagen por Resonancia Magnética , Diagnóstico Prenatal/métodos , Anomalías Múltiples , Adulto , Agenesia del Cuerpo Calloso/diagnóstico , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/patología , Enfermedades Cerebelosas/diagnóstico , Cerebelo/anomalías , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/patología , Infecciones por Citomegalovirus/diagnóstico , Anomalías del Ojo/diagnóstico , Femenino , Enfermedades Fetales/patología , Edad Gestacional , Holoprosencefalia/diagnóstico , Humanos , Enfermedades Renales Quísticas/diagnóstico , Embarazo , Retina/anomalías , Disrafia Espinal/diagnósticoRESUMEN
Sirenomelia and VACTERL association are defects of blastogenesis of unknown cause. Although they appear clinically distinct, some epidemiological and experimental studies suggest a common pathogenetic mechanism. We report on the reproductive history of a 28-year-old obese, diabetic mother who had three pregnancies. The first resulted in the birth of a sirenomelic child, the second in a miscarriage, while the third was terminated for fetal malformations, diagnosed post-mortem as VACTERL association. This observation supports the relationship between sirenomelia and VACTERL, which probably represent the two ends of the same phenotypic spectrum. Their occurrence in the same sibship also indicates a possible common cause. The coexistence with maternal diabetes seems more than a chance occurrence and the constellation of malformations observed in the present family may be explained as the pleiotropic effect of the same teratogenic agent interacting with genetic predisposition to diabetes and/or obesity.
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Anomalías Múltiples/patología , Diabetes Gestacional/patología , Ectromelia/complicaciones , Anomalías Múltiples/diagnóstico por imagen , Adulto , Ectromelia/diagnóstico por imagen , Resultado Fatal , Femenino , Feto/anomalías , Feto/diagnóstico por imagen , Humanos , Recién Nacido , Masculino , Embarazo , RadiografíaRESUMEN
INTRODUCTION: KIAA0586 variants have been associated to short-rib thoracic dysplasia, an autosomal recessive skeletal ciliopathy characterized by a narrow thorax, short limbs, and radiological skeletal abnormalities. PATIENT CONCERNS: Patients 1 and 2 were two Roma Gypsy siblings presenting thoracic dysplasia and a combination of oral cavity anomalies. DIAGNOSIS: A custom NGS gene panel, including genes associated to skeletal ciliopathies, identified the homozygous KIAA0586 splicing variant c.1815G>A (p.Gln605Gln) in both siblings, confirming the clinical diagnosis of short-rib-polydactyly. INTERVENTION: Patients were transferred to neonatal intensive care unit and received life-support treatment. OUTCOMES: Patients 1 and 2 died after few hours and 1 month of birth, respectively, because of respiratory failure related with the disease. CONCLUSION: We report two patients affected by short-rib polydactyly syndrome and overlapping phenotype with oral-facial-digital syndrome associated with the c.1815G>A variant in KIAA0586, suggesting a quite peculiar genotype-phenotype correlation.
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Proteínas de Ciclo Celular/genética , Síndromes Orofaciodigitales/complicaciones , Síndromes Orofaciodigitales/genética , Síndrome de Costilla Pequeña y Polidactilia/complicaciones , Síndrome de Costilla Pequeña y Polidactilia/genética , Ciliopatías , Humanos , Recién Nacido , Italia , Masculino , Fenotipo , Romaní , HermanosRESUMEN
Craniosynostosis is an etiologically heterogeneous malformation, which may present as an isolated finding or in association with other anomalies. The concurrence of craniosynostosis together with specific central nervous system, abdominal, genital, and limb malformations defines the Fontaine-Farriaux syndrome, described so far in only two patients. We report on a stillborn who mainly presented severe intrauterine growth retardation, bilateral coronal synostosis, generalized nail hypo/aplasia more evident on the posterior side, tapered digits, mild cutaneous syndactyly, abdominal muscle hypoplasia, micropenis and bilateral cryptorchidism. Skeletal radiographs revealed universal platyspondyly and necropsy findings comprised intestinal malrotation, abnormal cortical gyral formation, periventricular heterotopia, and cerebellar hypoplasia. Comparison between the present and the two previously described patients demonstrates that our case shows a combination of features strikingly resembling the original description. Conversely, the second reported patient shows a very atypical phenotype and is, most probably, affected by a distinct clinical entity. The triad of craniosynostosis, anonychia, and abdominal muscle hypo/aplasia emerges as the most consistent core phenotype, although skeletal and brain anomalies are relevant ancillary findings. An in-depth differential diagnosis with other partially overlapping conditions is carried out.
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Anomalías Múltiples/diagnóstico , Craneosinostosis/complicaciones , Craneosinostosis/diagnóstico , Cavidad Abdominal/anomalías , Cavidad Abdominal/patología , Anomalías Múltiples/patología , Adulto , Enfermedades del Desarrollo Óseo/complicaciones , Enfermedades del Desarrollo Óseo/patología , Enfermedades del Sistema Nervioso Central/congénito , Enfermedades del Sistema Nervioso Central/patología , Craneosinostosis/patología , Femenino , Humanos , Recién Nacido , Uñas Malformadas/complicaciones , Uñas Malformadas/patología , Mortinato , SíndromeRESUMEN
Endometrial cancer is the most common neoplasia of the female reproductive system, with the highest incidence among uterine malignancies, and is rarely associated with pregnancy. Thirty-five cases of pregnancy-associated endometrial cancer have been reported in literature, of which ours represents the 20th case diagnosed during the first trimester. A 39-year-old woman, gravida 4, para 2, was diagnosed with a focal, well- to moderately differentiated endometrial adenocarcinoma (International Federation of Gynecology and Obstetrics stage IA and grades G1 and G2) after dilatation and curettage (D&C) for a spontaneous abortion. The patient underwent progestational therapy and follow-up hysteroscopies and D&C to preserve fertility; she is alive and well 18 months after diagnosis. Recurrence of endometrial cancer coexisting with early pregnancy has not been reported in the literature. Conservative therapy for early endometrial cancer, diagnosed at the time of pregnancy, may be an option. Routine histologic examination after D&C performed for spontaneous abortion seems advisable.
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Adenocarcinoma/diagnóstico , Neoplasias Endometriales/diagnóstico , Complicaciones Neoplásicas del Embarazo/diagnóstico , Adulto , Femenino , Humanos , Hallazgos Incidentales , Embarazo , Primer Trimestre del Embarazo , Factores de TiempoRESUMEN
We present histological and molecular analyses of the developing human cerebellum from 30 days after conception to 9 months after birth. Differences in developmental patterns between humans and mice include spatiotemporal expansion of both ventricular and rhombic lip primary progenitor zones to include subventricular zones containing basal progenitors. The human rhombic lip persists longer through cerebellar development than in the mouse and undergoes morphological changes to form a progenitor pool in the posterior lobule, which is not seen in other organisms, not even in the nonhuman primate the macaque. Disruptions in human rhombic lip development are associated with posterior cerebellar vermis hypoplasia and Dandy-Walker malformation. The presence of these species-specific neural progenitor populations refines our insight into human cerebellar developmental disorders.
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Cerebelo/embriología , Cerebelo/crecimiento & desarrollo , Células Madre/citología , Animales , Síndrome de Dandy-Walker , Humanos , Ratones , Malformaciones del Sistema Nervioso , Análisis Espacio-Temporal , Especificidad de la Especie , TranscriptomaRESUMEN
Nager syndrome, or acrofacial dysostosis type 1 (AFD1), is a rare multiple malformation syndrome characterized by hypoplasia of first and second branchial arches derivatives and appendicular anomalies with variable involvement of the radial/axial ray. In 2012, AFD1 has been associated with dominant mutations in SF3B4. We report a 22-week-old fetus with AFD1 associated with diaphragmatic hernia due to a previously unreported SF3B4 mutation (c.35-2A>G). Defective diaphragmatic development is a rare manifestation in AFD1 as it is described in only 2 previous cases, with molecular confirmation in 1 of them. Our molecular finding adds a novel pathogenic splicing variant to the SF3B4 mutational spectrum and contributes to defining its prenatal/fetal phenotype.
RESUMEN
Subependymal heterotopia (SEH) is a neuronal migration disorder characterized by nodules of gray matter along the lateral ventricular walls and often associated with other brain malformations. We present two cases of SEH associated with ventriculomegaly and cerebellar abnormalities diagnosed by fetal magnetic resonance imaging (MRI) at 20 and 23 weeks' gestation respectively. Fetal MRI findings of this association of abnormalities have never been reported in literature. This report emphasizes the role of fetal MRI in recognition of subependymal heterotopia and other associated brain anomalies at early age of gestation along with its importance for a more targeted counseling and management strategies.
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Encefalopatías/diagnóstico , Encéfalo/anomalías , Enfermedades Fetales/diagnóstico , Malformaciones del Desarrollo Cortical del Grupo II/diagnóstico , Adulto , Cerebelo/anomalías , Femenino , Humanos , Hidrocefalia/diagnóstico , Imagen por Resonancia Magnética/métodos , Diagnóstico Prenatal/métodosRESUMEN
BACKGROUND: Thrombocytopenia-absent radius syndrome is a rare autosomal recessive disorder characterized by megakaryocytic thrombocytopenia and longitudinal limb deficiencies mostly affecting the radial ray. Most patients are compound heterozygotes for a 200 kb interstitial microdeletion in 1q21.1 and a hypomorphic allele in RBM8A, mapping in the deleted segment. At the moment, the complete molecular characterization of thrombocytopenia-absent radius syndrome is limited to a handful of patients mostly ascertained in the pediatric age CASE PRESENTATION: We report on a fetus with bilateral upper limb deficiency found at standard prenatal ultrasound examination. The fetus had bilateral radial agenesis and humeral hypo/aplasia with intact thumbs, micrognathia and urinary anomalies, indicating thrombocytopenia-absent radius syndrome. Molecular studies demonstrated compound heterozygosity for the 1q21.1 microdeletion and the RBM8A rs139428292 variant at the hemizygous state, inherited from the mother and father, respectively CONCLUSION: The molecular information allowed prenatal diagnosis in the following pregnancy resulting in the birth of a healthy carrier female. A review was carried out with the attempt to the trace the fetal ultrasound presentation of thrombocytopenia-absent radius syndrome and discussing opportunities for second-tier molecular studies within a multidisciplinary setting.
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Anomalías Múltiples/genética , Alelos , Feto/patología , Heterocigoto , Megalencefalia/genética , Diagnóstico Prenatal , Proteínas de Unión al ARN/genética , Trombocitopenia/genética , Deformidades Congénitas de las Extremidades Superiores/genética , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/patología , Adulto , Autopsia , Deleción Cromosómica , Cromosomas Humanos Par 1/diagnóstico por imagen , Cromosomas Humanos Par 1/genética , Hibridación Genómica Comparativa , Síndromes Congénitos de Insuficiencia de la Médula Ósea , Resultado Fatal , Femenino , Feto/metabolismo , Humanos , Masculino , Megalencefalia/diagnóstico por imagen , Megalencefalia/patología , Linaje , Embarazo , Radiografía , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/patología , Síndrome , Trombocitopenia/diagnóstico por imagen , Trombocitopenia/patología , Deformidades Congénitas de las Extremidades Superiores/diagnóstico por imagen , Deformidades Congénitas de las Extremidades Superiores/patologíaRESUMEN
OBJECTIVE: To evaluate histomorphometric vascular characteristics from samples obtained by chorionic villus sampling (CVS) in pregnancies with low serum pregnancy-associated plasma protein-A (PAPP-A) levels and to relate these findings to three-dimensional (3D) placental volume and power Doppler vascularization. METHODS: Immediately before CVS, placental 3D-power Doppler ultrasonography was performed at 11 + 0 to 13 + 6 weeks in 12 pregnancies with PAPP-A concentrations <0.3 multiples of median (MoM) as well as in 11 control women. Using a standardized setting placental volume, vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured. Histomorphometric parameters of villi were blindly evaluated with a video-computerized-image-analysis system. RESULTS: Pregnancies with low PAPP-A showed a significantly reduced number of capillary vessels per villus cross-section (p = 0.005) and a smaller capillary diameter (p = 0.041). Placental vascular indices were significantly related to the number of fetal capillary vessels per villus (VI: r = 0.51, p = 0.03; FI: r = 0.48, p = 0.04; VFI: r = 0.56, p = 0.01). CONCLUSIONS: Differences in placental vascularization are present in first trimester in pregnancies with low PAPP-A and they are associated to altered 3D placental Doppler indices.
Asunto(s)
Vellosidades Coriónicas/anatomía & histología , Placenta/irrigación sanguínea , Placenta/diagnóstico por imagen , Primer Trimestre del Embarazo/sangre , Proteína Plasmática A Asociada al Embarazo/metabolismo , Ultrasonografía Prenatal/métodos , Vellosidades Coriónicas/diagnóstico por imagen , Vellosidades Coriónicas/ultraestructura , Muestra de la Vellosidad Coriónica , Femenino , Edad Gestacional , Humanos , Recién Nacido , Circulación Placentaria/fisiología , Embarazo , Primer Trimestre del Embarazo/metabolismo , Proteína Plasmática A Asociada al Embarazo/análisis , Ultrasonografía Doppler/métodosRESUMEN
We report the clinical features and pathological findings in 9 cases of intrapartum and early neonatal death associated with embolism of brain tissue to the pulmonary and systemic circulation following difficult delivery. All except 1 of the cases in this series were born at, or near to, term, were vertex presentations, and were normally grown. All followed instrumental delivery and in 5, at least one mode of assisted delivery had failed. Whilst some evidence of cranial trauma was present in 7 cases, only 3 had skull fractures and 7 showed intracranial hemorrhage, although this was described as minor in 3. Emboli of brain tissue were identified in the pulmonary circulation in all cases. Fragments of brain were also seen in vessels of other organs, in particular the heart, in 6 cases. Emboli were highlighted by immunostaining for glial fibrillary acid protein. Brain emboli should be sought in all post mortems of unexplained intrapartum or early neonatal death following difficult delivery, even in the absence of overt cranial trauma. Disseminated intravascular coagulation is a frequent association. Extensive sampling for histology, particularly of the lungs and coronary vessels, is essential if this condition is not to be missed.