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Ultrasound in Obstetrics & Gynecology :... Feb 2021Most brain abnormalities are present in the first trimester, but only a few are detected so early in gestation. According to current recommendations for first-trimester... (Review)
Review
Most brain abnormalities are present in the first trimester, but only a few are detected so early in gestation. According to current recommendations for first-trimester ultrasound, the fetal head structures that should be visualized are limited to the cranial bones, the midline falx and the choroid-plexus-filled ventricles. Using this basic approach, almost all cases of acrania, alobar holoprosencephaly and cephalocele are detected. However, the majority of other fetal brain abnormalities remain undiagnosed until the midtrimester. Such anomalies would be potentially detectable if the sonographic study were to be extended to include additional anatomic details not currently included in existing guidelines. The aim of this review article is to describe how best to assess the normal fetal brain by first-trimester expert multiplanar neurosonography and to demonstrate the early sonographic findings that characterize some major fetal brain abnormalities. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Encephalocele; Female; Fetus; Holoprosencephaly; Humans; Nervous System Malformations; Pregnancy; Pregnancy Trimester, First; Ultrasonography, Prenatal
PubMed: 33049801
DOI: 10.1002/uog.23149 -
Life (Basel, Switzerland) May 2022This paper describes the contemporary state of knowledge regarding processes that regulate normal development of the embryonic-fetal central nervous system (CNS). The... (Review)
Review
This paper describes the contemporary state of knowledge regarding processes that regulate normal development of the embryonic-fetal central nervous system (CNS). The processes are described according to the developmental timetable: dorsal induction, ventral induction, neurogenesis, neuronal migration, post-migration neuronal development, and cortical organization. We review the current literature on CNS malformations associated with these regulating processes. We specifically address neural tube defects, holoprosencephaly, malformations of cortical development (including microcephaly, megalencephaly, lissencephaly, cobblestone malformations, gray matter heterotopia, and polymicrogyria), disorders of the corpus callosum, and posterior fossa malformations. Fetal ventriculomegaly, which frequently accompanies these disorders, is also reviewed. Each malformation is described with reference to the etiology, genetic causes, prenatal sonographic imaging, associated anomalies, differential diagnosis, complimentary diagnostic studies, clinical interventions, neurodevelopmental outcome, and life quality.
PubMed: 35743840
DOI: 10.3390/life12060809 -
Brain : a Journal of Neurology Sep 2019Marked by incomplete division of the embryonic forebrain, holoprosencephaly is one of the most common human developmental disorders. Despite decades of phenotype-driven...
Marked by incomplete division of the embryonic forebrain, holoprosencephaly is one of the most common human developmental disorders. Despite decades of phenotype-driven research, 80-90% of aneuploidy-negative holoprosencephaly individuals with a probable genetic aetiology do not have a genetic diagnosis. Here we report holoprosencephaly associated with variants in the two X-linked cohesin complex genes, STAG2 and SMC1A, with loss-of-function variants in 10 individuals and a missense variant in one. Additionally, we report four individuals with variants in the cohesin complex genes that are not X-linked, SMC3 and RAD21. Using whole mount in situ hybridization, we show that STAG2 and SMC1A are expressed in the prosencephalic neural folds during primary neurulation in the mouse, consistent with forebrain morphogenesis and holoprosencephaly pathogenesis. Finally, we found that shRNA knockdown of STAG2 and SMC1A causes aberrant expression of HPE-associated genes ZIC2, GLI2, SMAD3 and FGFR1 in human neural stem cells. These findings show the cohesin complex as an important regulator of median forebrain development and X-linked inheritance patterns in holoprosencephaly.
Topics: Adolescent; Animals; Cell Cycle Proteins; Child; Child, Preschool; Chromosomal Proteins, Non-Histone; Female; Holoprosencephaly; Humans; Infant; Infant, Newborn; Male; Mice; Mice, Inbred C57BL; Cohesins
PubMed: 31334757
DOI: 10.1093/brain/awz210 -
Ultrasound in Obstetrics & Gynecology :... Oct 2019To examine the performance of the routine 11-13-week scan in detecting fetal non-chromosomal abnormalities.
OBJECTIVE
To examine the performance of the routine 11-13-week scan in detecting fetal non-chromosomal abnormalities.
METHODS
This was a retrospective study of prospectively collected data from 100 997 singleton pregnancies attending for a routine ultrasound examination of fetal anatomy, performed according to a standardized protocol, at 11-13 weeks' gestation. All continuing pregnancies had an additional scan at 18-24 weeks and 71 754 had a scan at either 30-34 or 35-37 weeks. The final diagnosis of fetal abnormality was based on the results of postnatal examination in cases of live birth and on the findings of the last ultrasound examination in cases of pregnancy termination, miscarriage or stillbirth. The performance of the 11-13-week scan in the detection of fetal abnormalities was determined.
RESULTS
The study population contained 1720 (1.7%) pregnancies with a fetal abnormality, including 474 (27.6%) detected on the first-trimester scan, 926 (53.8%) detected on the second-trimester scan and 320 (18.6%) detected in the third trimester or postnatally. At 11-13 weeks' gestation, we diagnosed all cases of acrania, alobar holoprosencephaly, encephalocele, tricuspid or pulmonary atresia, pentalogy of Cantrell, ectopia cordis, exomphalos, gastroschisis and body-stalk anomaly and > 50% of cases of open spina bifida, hypoplastic left heart syndrome, atrioventricular septal defect, complex heart defect, left atrial isomerism (interrupted inferior vena cava with normal intracardiac anatomy), lower urinary tract obstruction, absence of extremities, fetal akinesia deformation sequence and lethal skeletal dysplasia. Common abnormalities that were detected in < 10% of cases at 11-13 weeks included ventriculomegaly, agenesis of the corpus callosum, isolated cleft lip, congenital pulmonary airway malformation, ventricular septal defect, abdominal cysts, unilateral renal agenesis or multicystic kidney, hydronephrosis, duplex kidney, hypospadias and talipes.
CONCLUSIONS
A routine 11-13-week scan, carried out according to a standardized protocol, can identify many severe non-chromosomal fetal abnormalities. A summary statistic of the performance of the first-trimester scan is futile because some abnormalities are always detectable, whereas others are either non-detectable or sometimes detectable. To maximize prenatal detection of abnormalities, additional scans in both the second and third trimesters are necessary. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Adult; Congenital Abnormalities; Female; Fetus; Gestational Age; Humans; Nuchal Translucency Measurement; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Prenatal Care; Retrospective Studies; Ultrasonography, Prenatal
PubMed: 31408229
DOI: 10.1002/uog.20844 -
Autopsy & Case Reports 2017
PubMed: 29259929
DOI: 10.4322/acr.2017.033 -
Revista Paulista de Pediatria : Orgao... 2023To evaluate radiological (gestational and perinatal) and neonatal signs of patients with Patau syndrome and semilobar holoprosencephaly, as well as to report the...
OBJECTIVE
To evaluate radiological (gestational and perinatal) and neonatal signs of patients with Patau syndrome and semilobar holoprosencephaly, as well as to report the association of both pathologies.
CASE DESCRIPTION
This case report is about a female infant, born at term with trisomy of the chromosome 13 and semilobar holoprosencephaly, with thalamic fusion and a single cerebral ventricle, in addition to several other changes that worsened the patient's prognosis.
COMMENTS
Chromosome 13 trisomy is a genetic alteration that leads to the symptoms that determines Patau syndrome. In this syndrome, cardiovascular, urogenital, central nervous system, facial structure and intellectual impairment are common, in addition to problems in limb formation, such as decreased humerus and femur length, polydactyly, hypotelorism and low ear implantation. It is estimated, however, that holoprosencephaly is present in only 24 to 45% of the patients with trisomy 13.
Topics: Infant, Newborn; Pregnancy; Infant; Humans; Female; Holoprosencephaly; Trisomy 13 Syndrome; Trisomy; Polydactyly; Mutation; Chromosomes, Human, Pair 13
PubMed: 36921175
DOI: 10.1590/1984-0462/2023/41/2022027 -
American Journal of Medical Genetics.... Jun 2018Nonchromosomal, nonsyndromic holoprosencephaly (NCNS-HPE) has traditionally been considered as a condition of brain and craniofacial maldevelopment. In this review, we... (Review)
Review
Nonchromosomal, nonsyndromic holoprosencephaly (NCNS-HPE) has traditionally been considered as a condition of brain and craniofacial maldevelopment. In this review, we present the results of a comprehensive literature search supporting a wide spectrum of extracephalic manifestations identified in patients with NCNS-HPE. These manifestations have been described in case reports and in large cohorts of patients with "single-gene" mutations, suggesting that the NCNS-HPE phenotype can be more complex than traditionally thought. Likely, a complex network of interacting genetic variants and environmental factors is responsible for these systemic abnormalities that deviate from the usual brain and craniofacial findings in NCNS-HPE. In addition to the systemic consequences of pituitary dysfunction (as a direct result of brain midline defects), here we describe a number of extracephalic findings of NCNS-HPE affecting various organ systems. It is our goal to provide a guide of extracephalic features for clinicians given the important clinical implications of these manifestations for the management and care of patients with HPE and their mutation-positive relatives. The health risks associated with some manifestations (e.g., fatty liver disease) may have historically been neglected in affected families.
Topics: Abnormalities, Multiple; Biomarkers; Disease Susceptibility; Endocrine System Diseases; Genetic Predisposition to Disease; Hedgehog Proteins; Holoprosencephaly; Humans; Mutation; Phenotype; Signal Transduction
PubMed: 29761634
DOI: 10.1002/ajmg.c.31616