RESUMEN
Microcephaly with simplified gyral pattern (MSG) is an intrinsic genetic central nervous system disorder, characterized by microcephaly (a reduction of brain volume) and a simplified gyral pattern (a reduced number of gyri and shallow sulci associated with normal cortical thickness and neuroanatomical architecture), related to a reduced number of neuronal progenitors in the germinal matrix. We report the first prenatal series of MSG and define the prenatal imaging pattern, which should inform diagnosis and guide prenatal counseling in cases of fetal microcephaly. In this single-center retrospective study of fetuses with MSG, we assessed features on ultrasound and magnetic resonance imaging (MRI), as well as genetic and neuropathological/postnatal data. We included eight patients who had been referred following observation of microcephaly. Ultrasound examination confirmed microcephaly, with a mean growth delay in head circumference of 3.4 weeks, associated with both a lack of gyration and a lack of opercularization of the Sylvian fissure and without any extracephalic anomaly. Fetal brain MRI confirmed lack of gyration with normal cortical thickness and normal intensity of the white matter in all cases. These MRI features led to exclusion of migration/corticogenesis disorders (lissencephaly/polymicrogyria), instead suggesting MSG. The posterior fossa was normal in seven of the eight cases. The corpus callosum was thin in four cases, hypoplastic in two and dysgenetic in two. In four cases, the pregnancy was terminated. The diagnosis of MSG was confirmed from neuropathological and postnatal MRI data. MSG was associated with a genetic diagnosis of RTTN (n = 1) and ASPM (n = 2) biallelic variants in three of the six cases in which genetic work-up was performed. Mild or moderate intellectual deficit with speech delay was present in the three surviving children who were at least 5 years of age at their last examination, without seizures. In conclusion, in the presence of isolated fetal microcephaly with lack of gyration on ultrasound, fetal cerebral MRI is key to diagnosing MSG, which, in the majority of cases, affects the supratentorial space exclusively, and to ruling out other cortical malformations that show a similar sonographic pattern. In addition to imaging, genetic assessment may guide prenatal counseling, since the prenatal prognosis of MSG is different from that of both diffuse polymicrogyria and lissencephaly. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Asunto(s)
Lisencefalia , Microcefalia , Malformaciones del Sistema Nervioso , Polimicrogiria , Niño , Femenino , Embarazo , Humanos , Microcefalia/diagnóstico por imagen , Estudios Retrospectivos , Diagnóstico Prenatal , Imagen por Resonancia Magnética/métodos , Ultrasonografía Prenatal/métodosAsunto(s)
Quistes , Quistes/diagnóstico por imagen , Quistes/cirugía , Femenino , Humanos , Embarazo , Diagnóstico PrenatalRESUMEN
OBJECTIVES: To describe clinical and molecular findings in a French multicenter cohort of fetuses with prenatal diagnosis of congenital abnormality and suspicion of a localized overgrowth disorder (LOD) suggestive of genetic variants in the PI3K-AKT-mTOR signaling pathway. METHODS: We analyzed retrospectively data obtained between 1 January 2013 and 1 May 2020 from fetuses with brain and/or limb overgrowth referred for molecular diagnosis of PI3K-AKT-mTOR pathway genes by next-generation sequencing (NGS) using pathological tissue obtained by fetal autopsy. We also assessed the diagnostic yield of amniotic fluid. RESULTS: During the study period, 21 subjects with LOD suspected of being secondary to a genetic variant of the PI3K-AKT-mTOR pathway were referred for analysis. Of these, 17 fetuses had brain overgrowth, including six with isolated megalencephaly (MEG) and 11 with hemimegalencephaly (HMEG). Of the six with MEG, germline variants were identified in four cases, in either PIK3R2, AKT3 or MTOR, and a postzygotic PIK3R2 variant was found in the other two cases. Of the 11 with HMEG, a postzygotic PIK3CA variant was found in three fetuses with extracerebral features of PIK3CA-related overgrowth spectrum, and in seven fetuses with isolated HMEG. No pathogenic variant was identified in the 11th case with HMEG. Four fetuses with limb overgrowth also had one or more lymphatic malformations (LM) and harbored a postzygotic PIK3CA variant. NGS on cultured amniocytes performed in 10 cases, of which nine had been found positive on analysis of pathological fetal tissue, showed variants in four, in either PIK3CA, PIK3R2 or AKT3. CONCLUSIONS: Isolated MEG or HMEG may lead to identification of genetic variants in the PI3K-AKT-mTOR signaling pathway. Cases of limb overgrowth and LM or isolated HMEG are likely associated with PIK3CA variants. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Asunto(s)
Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Humanos , Mutación , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Estudios Retrospectivos , Transducción de Señal/genética , Serina-Treonina Quinasas TOR/genéticaRESUMEN
To illustrate the prenatal cerebral imaging features associated with tubulinopathy, we report on five affected fetuses from unrelated families, with a de-novo heterozygous variant in a tubulin gene (TUBA1A, TUBB2B or TUBB3). We identified two distinct prenatal imaging patterns related to tubulinopathy: a severe form, characterized by enlarged germinal matrices, microlissencephaly and a kinked brainstem; and a mild form which has not been reported previously in the prenatal literature. The latter form is associated with non-specific features, including an asymmetric brainstem, corpus callosal dysgenesis, a lack of Sylvian fissure operculization and distortion of the anterior part of the interhemispheric fissure with subsequent impacted medial borders of the frontal lobes, the combination of which, in the absence of additional extracerebral anomalies, is highly suggestive of tubulinopathy. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.
Asunto(s)
Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/embriología , Malformaciones del Desarrollo Cortical/diagnóstico por imagen , Malformaciones del Desarrollo Cortical/embriología , Ultrasonografía Prenatal , Tronco Encefálico/anomalías , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/embriología , Corteza Cerebral/anomalías , Femenino , Feto/anomalías , Feto/diagnóstico por imagen , Feto/embriología , Variación Genética , Humanos , Malformaciones del Desarrollo Cortical/genética , Ilustración Médica , Microcefalia/diagnóstico por imagen , Microcefalia/embriología , Embarazo , Tubulina (Proteína)/genéticaAsunto(s)
Neoplasias Encefálicas/patología , Tumores Neuroectodérmicos/diagnóstico por imagen , Adulto , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/embriología , Fosa Craneal Posterior , Errores Diagnósticos , Imagen de Difusión por Resonancia Magnética , Resultado Fatal , Femenino , Humanos , Hidrocefalia/diagnóstico , Lactante , Recién Nacido , Tumores Neuroectodérmicos/embriología , Tumores Neuroectodérmicos/patología , EmbarazoRESUMEN
PURPOSE: Developmental and epileptic encephalopathies (DEEs) are severe clinical conditions characterized by stagnation or decline of cognitive and behavioral abilities preceded, accompanied or followed by seizures. Because DEEs are clinically and genetically heterogeneous, next-generation sequencing, especially exome sequencing (ES), is becoming a first-tier strategy to identify the molecular etiologies of these disorders. METHODS: We combined ES analysis and international data sharing. RESULTS: We identified 11 unrelated individuals with DEE and de novo heterozygous truncating variants in the interferon regulatory factor 2-binding protein-like gene (IRF2BPL). The 11 individuals allowed for delineation of a consistent neurodevelopmental disorder characterized by mostly normal initial psychomotor development followed by severe global neurological regression and epilepsy with nonspecific electroencephalogram (EEG) abnormalities and variable central nervous system (CNS) anomalies. IRF2BPL, also known as enhanced at puberty protein 1 (EAP1), encodes a transcriptional regulator containing a C-terminal RING-finger domain common to E3 ubiquitin ligases. This domain is required for its repressive and transactivating transcriptional properties. The variants identified are expected to encode a protein lacking the C-terminal RING-finger domain. CONCLUSIONS: These data support the causative role of truncating IRF2BPL variants in pediatric neurodegeneration and expand the spectrum of transcriptional regulators identified as molecular factors implicated in genetic developmental and epileptic encephalopathies.
Asunto(s)
Proteínas Portadoras/genética , Epilepsia/genética , Trastornos del Neurodesarrollo/genética , Proteínas Nucleares/genética , Convulsiones/genética , Adolescente , Adulto , Sistema Nervioso Central/diagnóstico por imagen , Sistema Nervioso Central/patología , Niño , Electroencefalografía , Epilepsia/diagnóstico por imagen , Epilepsia/fisiopatología , Femenino , Heterocigoto , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Mutación , Trastornos del Neurodesarrollo/diagnóstico por imagen , Trastornos del Neurodesarrollo/fisiopatología , Fenotipo , Convulsiones/diagnóstico por imagen , Convulsiones/fisiopatología , Secuenciación del Exoma , Adulto JovenAsunto(s)
Codón sin Sentido , Coloboma/genética , Proteínas Hedgehog/genética , Discapacidad Intelectual/genética , Microcefalia/genética , Fenotipo , Niño , Coloboma/diagnóstico , Facies , Predisposición Genética a la Enfermedad , Humanos , Discapacidad Intelectual/diagnóstico , Imagen por Resonancia Magnética , Masculino , Microcefalia/diagnóstico , Linaje , Secuenciación del ExomaAsunto(s)
Malformaciones Arteriovenosas/diagnóstico por imagen , Capilares/anomalías , Mancha Vino de Oporto/diagnóstico por imagen , Diagnóstico Prenatal , Enfermedades Cutáneas Vasculares/diagnóstico por imagen , Adulto , Malformaciones Arteriovenosas/genética , Malformaciones Arteriovenosas/patología , Capilares/diagnóstico por imagen , Capilares/patología , Femenino , Pruebas Genéticas , Humanos , Recién Nacido , Mancha Vino de Oporto/genética , Mancha Vino de Oporto/patología , Embarazo , Enfermedades Cutáneas Vasculares/genética , Enfermedades Cutáneas Vasculares/patologíaRESUMEN
We report the first series of cases of pericallosal curvilinear lipoma (CL) diagnosed prenatally and highlight the limitations in identifying a specific prenatal imaging pattern using ultrasound and magnetic resonance imaging (MRI). In all five of our cases, on ultrasound, the main feature leading to referral was a short corpus callosum. This subtle callosal dysgenesis was associated with a band of hyperechogenicity surrounding the corpus callosum, mimicking the pericallosal sulcus, which increased in size during the third trimester in three of the four cases in which sonographic follow-up was performed. On T2-weighted MRI, this band showed typical hypointensity in all cases; in contrast, on T1-weighted imaging, in only one case was there hyperintensity, suggestive of fat, as seen typically in the postnatal period. For appropriate prenatal counseling regarding outcome, it is important to identify or rule out CL when mild corpus callosal dysgenesis is observed. One should be aware of subtle diagnostic findings, such as a thin band of echogenicity surrounding the corpus callosum that is seen as a band of hypointensity on T2-weighted fetal MRI, and which may increase in size during gestation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Asunto(s)
Agenesia del Cuerpo Calloso/diagnóstico por imagen , Neoplasias Encefálicas/diagnóstico por imagen , Cuerpo Calloso/diagnóstico por imagen , Lipoma/diagnóstico por imagen , Imagen por Resonancia Magnética , Ultrasonografía Prenatal , Adulto , Agenesia del Cuerpo Calloso/embriología , Agenesia del Cuerpo Calloso/patología , Neoplasias Encefálicas/congénito , Neoplasias Encefálicas/embriología , Cuerpo Calloso/embriología , Cuerpo Calloso/patología , Femenino , Asesoramiento Genético , Humanos , Recién Nacido , Lipoma/congénito , Lipoma/embriología , Masculino , EmbarazoAsunto(s)
Criocirugía , Mano/cirugía , Hemangioendotelioma/cirugía , Neoplasias de los Tejidos Blandos/cirugía , Adolescente , Femenino , Hemangioendotelioma/diagnóstico por imagen , Humanos , Dolor/etiología , Dolor/cirugía , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Ultrasonografía IntervencionalRESUMEN
Taybi-Linder syndrome (TALS, OMIM 210710) is a rare autosomal recessive disorder belonging to the group of microcephalic osteodysplastic primordial dwarfisms (MOPD). This syndrome is characterized by short stature, skeletal anomalies, severe microcephaly with brain malformations and facial dysmorphism, and is caused by mutations in RNU4ATAC. RNU4ATAC is transcribed into a non-coding small nuclear RNA which is a critical component of the minor spliceosome. We report here four foetuses and four unrelated patients with RNU4ATAC mutations. We provide antenatal descriptions of this rare syndrome including unusual features found in two twin foetuses with compound heterozygosity for two rare mutations who presented with mild intrauterine growth retardation and atypical dysmorphic facial features. We also carried out a literature review of the patients described up to now with RNU4ATAC mutations, affected either with TALS or Roifman syndrome, a recently described allelic disorder.
Asunto(s)
Anomalías Múltiples/genética , Cardiomiopatías/genética , Enanismo/genética , Retardo del Crecimiento Fetal/genética , Síndromes de Inmunodeficiencia/genética , Discapacidad Intelectual Ligada al Cromosoma X/genética , Microcefalia/genética , Osteocondrodisplasias/genética , ARN Nuclear Pequeño/genética , Enfermedades de la Retina/genética , Anomalías Múltiples/fisiopatología , Alelos , Cardiomiopatías/fisiopatología , Niño , Preescolar , Enanismo/fisiopatología , Femenino , Retardo del Crecimiento Fetal/fisiopatología , Feto , Humanos , Síndromes de Inmunodeficiencia/fisiopatología , Lactante , Recién Nacido , Masculino , Discapacidad Intelectual Ligada al Cromosoma X/fisiopatología , Microcefalia/fisiopatología , Mutación , Osteocondrodisplasias/fisiopatología , Fenotipo , Enfermedades de Inmunodeficiencia Primaria , Enfermedades de la Retina/fisiopatología , Empalmosomas/genéticaRESUMEN
OBJECTIVE: The aim of the study was to evaluate feasibility and reproducibility of fetal transcerebellar diameter measurement during second and third trimester ultrasound mass screening by junior and senior physicians. MATERIALS AND METHODS: A monocentric prospective study was conducted at the tertiary care teaching hospital in Lyon, including patients undergoing their second or third trimester planned ultrasound exam. For each patient, a resident and a senior practitioner measured each fetal transcerebellar diameter, during a blinded experiment, according to the transcerebellar plane described by the International Society of Ultrasound in Obstetrics and Gynecology. Images have been scored on 4 criteria. The inter-observer variability for transcerebellar diameter and image quality was assessed using an intra-class correlation coefficient. Image quality has been analyzed according to pregnancy term and to fetal presentation. RESULTS: Sixty-six patients were included, 44 patients before and 22 patients after 30 weeks. Inter-observer variability of transcerebellar diameter measurement was 0.4%. Inter-observer variability of image quality was 13.5%. Image quality was not significantly different between seniors and residents (P=0.06). Gestational age and fetal presentation did not affect significantly image quality (P=0.42) and (P=0.64) respectively. CONCLUSION: Transcerebellar diameter measurement during mass screening is simple and reliable. Posterior fossa abnormalities can be explored through its measurement.
Asunto(s)
Cerebelo/embriología , Ultrasonografía Prenatal , Cerebelo/diagnóstico por imagen , Estudios de Factibilidad , Femenino , Edad Gestacional , Humanos , Presentación en Trabajo de Parto , Tamizaje Masivo , Variaciones Dependientes del Observador , Embarazo , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
We report a specific sonographic cerebral pattern of cobblestone lissencephaly (CL) that has not been described previously. This pattern was encountered in four index cases and allowed prenatal diagnosis of CL associated with Walker-Warburg syndrome. The pattern included both an outer echogenic band with reduced pericerebral space, corresponding to an infra- and supratentorial extracortical layer of neuroglial overmigration on pathological examination, and a 'Z'-shaped appearance of the brainstem. This pattern was found as early as 14 weeks' gestation in one of our cases.
Asunto(s)
Lisencefalia de Cobblestone/diagnóstico por imagen , Síndrome de Walker-Warburg/diagnóstico por imagen , Adulto , Ecoencefalografía , Femenino , Humanos , Embarazo , Primer Trimestre del Embarazo , Segundo Trimestre del Embarazo , Ultrasonografía PrenatalRESUMEN
Management of vascular malformations and vascular tumors has recently been maximized by the establishment of an accurate clinical and histological classification and by the development of multidisciplinary expert consultations. Head and neck localizations of venous malformations are common, thus maxillo-facial surgeons should be aware of the characteristics of this pathology and the principles of its management. Diagnosis is mainly clinical and must be certified by Doppler-ultrasonography and contrast enhanced magnetic resonance imaging with T2 fat-saturation sequence. Therapeutic decision depends on the volume of the lesion, and on functional, cosmetic and psychological complaints. Sclerotherapy is now the preferred treatment of head and neck venous malformations. It is performed in specialized interventional radiology units by intralesional injections of sclerosing solution under fluoroscopic guidance. Surgery is useful in some cases, either on its own or following sclerotherapy. In case of bulky lesion, it is necessary to search for and prevent a severe coagulopathy before planning any intervention.