Holoprosencephaly in Patau Syndrome.

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.

Holoprosencefalia lobar en un recién nacido / Lobar Holoprosencephaly in A Newborn Infant

Introducción: La holoprosencefalia es la consecuencia directa de cambios genéticos o ambientales específicos que interrumpen la división de la línea media del prosencéfalo embrionario o prosencéfalo. Estas alteraciones pueden condicionar disímiles alteraciones fenotípicas en los seres humanos. Objetivo: Describir las manifestaciones clínicas de pacientes con holoprosencefalia y la conducta clínica y terapéutica en un neonato. Presentación del caso: Hijo de padres no consanguíneos, madre de 35 años de edad con antecedente de cervicitis y gestorragia en la segunda mitad del embarazo, y antecedentes familiares de diabetes mellitus y cardiopatía. El parto se produjo a término a las 37 semanas, distócico por cesárea secundaria a un hematoma retroplacentario. Se obtuvo un recién nacido del sexo masculino con presentación pelviana, peso de 3380 gramos y Apgar 9/9 al nacer. La cesárea se realizó en el Hospital Materno Sur Mariana Grajales Coello (área urbana) de Santiago de Cuba. En el recién nacido se observaron rasgos dismórficos principalmente cráneo-facial. No precisó reanimación, pero a los pocos minutos comenzó con cuadro de dificultad respiratoria e hiposaturación. Conclusiones: En la holoprosencefalia el diagnóstico posnatal se puede realizar mediante las características fenotípicas, las malformaciones faciales y los estudios neuroimagenológicos como el ultrasonido transfontanelar y la tomografía axial computarizada de cráneo. Los pacientes deben evaluarse y seguirse en la evolución por un equipo multidisciplinario de especialidades como otorrinolaringología, máxilo-facial, neuropediatría, consulta de neurodesarrollo, genética, fisiatría e imagenología(AU)

Introduction: Holoprosencephaly is the direct consequence of specific genetic or environmental changes that disrupt midline division of the embryonic prosencephalon or prosencephalon. These alterations can condition dissimilar phenotypic alterations in humans. Objective: To describe the clinical manifestations of patients with holoprosencephaly and the clinical and therapeutic behavior in a neonate. Case presentation: Child of non-consanguineous parents, 35-year-old mother with a history of cervicitis and gestation bleeding in the second half of pregnancy, and family history of diabetes mellitus and heart disease. Delivery was at term, at 37 weeks, dystocic by cesarean section secondary to a retroplacental hematoma. The result was a male newborn with breech presentation, weight 3380 grams and Apgar 9/9 at birth. The cesarean section was performed at the Hospital Materno Sur Mariana Grajales Coello (urban area) of Santiago de Cuba. Dysmorphic features were observed in the newborn, mainly craniofacial dysmorphic ones. He did not require resuscitation, but a few minutes later he presented respiratory distress and hyposaturation. Conclusions: In holoprosencephaly, postnatal diagnosis can be made by phenotypic features, facial malformations and neuroimaging studies such as transfontanellar ultrasound and cranial computed tomography. Patients should be evaluated and followed in evolution by a multidisciplinary team of specialties such as otorhinolaryngology, maxillofacial, neuropediatrics, neurodevelopmental consultation, genetics, physiatry and imaging(AU)

Síndrome del incisivo central maxilar medio único en neonato / Solitary median maxillary central incisor syndrome in neonates / Síndrome do incisivo central maxilar médio solitário em neonatos

Introducción: el síndrome del incisivo central maxilar medio único (SMMCI) es un trastorno de etiología desconocida, con base genética heterogénea, que se caracteriza por la erupción de un único incisivo central en el maxilar y que se puede relacionar con multitud de patologías y síndromes, entre los que destacan las alteraciones de la línea media, obstrucción nasal congénita, disfunción hipofisaria, talla baja y holoprosencefalia. Caso clínico: neonato mujer con síndrome dismórfico no filiado y obstrucción nasal congénita, que es diagnosticada de SMMCI tras consultar en repetidas ocasiones por cuadros de dificultad respiratoria y problemas para alimentarse. Conclusiones: el conocimiento de este raro síndrome es fundamental para la realización de un diagnóstico precoz por parte del equipo pediátrico y obstétrico, ya que un diagnóstico temprano es posible, mejorando la evaluación prenatal ecográfica, así como el adecuado manejo posnatal multidisciplinar posterior de nuestros pacientes.

Introduction: the Solitary Median Maxillary Central Incisor Syndrome (SMMCI) is a disorder of unknown etiology, with a heterogeneous genetic basis, characterized by the eruption of a single central incisor in the maxilla and that can be linked to various pathologies and syndromes, among which the alterations of the midline, congenital nasal obstruction, pituitary dysfunction, short stature and holoprosencephaly stand out. Clinical case: female newborns with unknown dysmorphic syndrome and congenital nasal obstruction, diagnosed with SMMCI after repeated consultations due to respiratory distress and feeding problems. Conclusions: understanding this rare syndrome is essential for an early diagnosis to be carried out by the pediatric and obstetric team, since it will improve the ultrasound prenatal assessment, as well as the adequate subsequent multidisciplinary postnatal patient management procedures.

Introdução: a síndrome do incisivo central maxilar médio solitário (SICMMS) é uma desordem de etiologia desconhecida, com base genética heterogênea, caracterizada pela erupção de um único incisivo central na maxila e que pode estar relacionada a uma infinidade de patologias e síndromes. onde se destacam alterações da linha média, obstrução nasal congênita, disfunção hipofisária, baixa estatura e holoprosencefalia. Caso clínico: recém-nascida com síndrome dismórfica de origem desconhecida e obstrução nasal congênita, diagnosticada com SICMSS após várias consultas por desconforto respiratório e problemas de alimentação. Conclusões: o conhecimento desta rara síndrome é essencial para que a equipe pediátrica e obstétrica possa fazer um diagnóstico precoce, pois ele pode melhorar a avaliação ultrassonográfica pré-natal, bem como o adequado manejo pós-natal multidisciplinar pós-natal dos pacientes.

Variante interhemisférica media de holoprosencefalia: diagnóstico mediante resonancia magnética fetal / The diagnosis of the middle interhemispheric variant of holoprosencephaly with fetal MRI

Las anomalías congénitas del sistema nervioso central constituyen un amplio grupo de malformaciones asociadas a una gran variedad de síndromes genéticos y anomalías cromosómicas, y una de las principales causas de morbimortalidad infantil. Dentro de ellas, la holoprosencefalia conlleva un trastorno de la diferenciación del prosencéfalo, con una falta completa o parcial de división entre los hemisferios cerebrales. Para su diagnóstico prenatal es fundamental la realización de pruebas de imagen y el conocimiento de los posibles hallazgos, debido a que su pronóstico es variable, comenzando normalmente con la ecografía y confirmando lo visualizado con la resonancia magnética.(AU)

Congenital anomalies of the central nervous system comprise a wide spectrum of malformations associated with a wide variety of genetic syndromes and chromosomal anomalies, and they are among the principal causes of morbidity and mortality in infants. Among these anomalies, holoprosencephaly arises from the complete or partial failure of the brain to divide into the cerebral hemispheres. Imaging tests are fundamental for the prenatal diagnosis of holoprosencephaly; the diagnostic process usually starts with sonography and then the findings are refined with fetal MRI. Radiologists need to be familiar with the possible findings because the prognosis varies.(AU)

Sonography of fetal holoprosencephaly: a guide to recognize the lesser varieties.

BACKGROUND: Alobar holoprosencephaly (HPE) is easily detected during a first-trimester screening examination, conversely, recognizing the lesser varieties may be difficult even in the second trimester. OBJECTIVES: To describe the imaging findings of a cohort of fetuses with holoprosencephaly (HPE) and to elucidate the appearances of the different anatomical varieties. MATERIALS AND METHODS: We reviewed medical records and stored images of pregnant women referred to our clinic because of a diagnosis or the suspicion of various forms of HPE. We reported the imaging characteristics, the presence of other associated anomalies, magnetic resonance findings, karyotype and autoptic examinations when available. RESULTS: Alobar forms show great distortion of normal brain anatomy, with a single ventricle detectable during the first trimester of pregnancy. Extracerebral, face and karyotype abnormalities are often associated. In semilobar and lobar forms the septum pellucidum is typically absent in axial planes, with fused frontal horns, while posterior fossa is often normal. At multiplanar neurosonogram, anomalies involving corpus callosum and cortex development can be detected. Face abnormalities are mild in lobar forms: receding forehead, various degrees of hypotelorism and the presence of a single central maxillary incisor are reported. CONCLUSIONS: The alobar forms are detectable since the first trimester, with a peculiar single ventricle and extremely frequent extracerebral and karyotype abnormalities. The semilobar and lobar forms are more challenging and the diagnosis is easily missed in a mid-trimester screening exam unless a careful evaluation of both cavum septi pellucidi and frontal horns as well is conducted.

Application of quantitative fluorescent polymerase chain reaction analysis for the rapid confirmation of trisomy 13 of maternal origin in a pregnancy with fetal holoprosencephaly, cyclopia, polydactyly, omphalocele and cell culture failure.

OBJECTIVE: We present the application of quantitative fluorescent polymerase chain reaction (QF-PCR) for the rapid confirmation of trisomy 13 of maternal origin in a pregnancy with fetal holoprosencephaly (HPE), cyclopia, polydactyly, omphalocele and cell culture failure. CASE REPORT: A 21-year-old, gravida 2, para 0, woman was referred for termination of the pregnancy at 17 weeks of gestation because of the abnormal ultrasound finding of alobar HPE. The pregnancy was subsequently terminated, and a 118-g malformed male fetus was delivered with cyclopia, bilateral postaxial polydactyly of the hands and ruptured omphalocele. Postmortem cell culture of the placental tissue and umbilical cord was not successful. The parental karyotypes were normal. QF-PCR analysis using the polymorphic DNA markers of D13S1810, D13S790 and D13S251 on the DNA extracted from placenta, umbilical cord and parental bloods showed trisomy 13 of maternal origin. CONCLUSION: Perinatal diagnosis of concomitant HPE, polydactyly and omphalocele should raise a suspicion of fetal trisomy 13. QF-PCR analysis is useful for rapid confirmation of trisomy 13 and the parental origin especially under the circumstance of cell culture failure, and the information acquired is very useful for genetic counseling of the parents.

Congenital complete arhinia with alobar holoprosencephaly.

Congenital arhinia is a life-threatening, rare craniofacial disorder, which, when not identified and managed early can cause severe respiratory distress at birth due to upper airway obstruction. Since neonates are obligate nasal breathers, simultaneous sucking and breathing requirement in neonates with arhinia leads to respiratory distress. Inspiration and expiration through the oral passage alone may result in thoracic retraction, thereby further exacerbating respiratory distress. We report a rare case of congenital complete arhinia with alobar holoprosencephaly in a 9-month-old. With no family history of congenital malformations, maternal risk factors and uneventful pregnancy, a term female neonate was delivered vaginally without immediate post-delivery respiratory distress. Examination revealed microcephaly, absent fontanelles, fused cranial sutures and bilateral microphthalmia. Breathing was spontaneous, with no immediate signs of respiratory distress. An additional diagnosis of alobar holoprosencephaly was made after a head computed tomography (CT) scan was done. Management included the initial stabilisation phase of supplemental oxygen and an orogastric tube for feeding. The baby did not require both tracheostomy and gastrostomy tubes, as she was not in severe respiratory distress requiring a tracheostomy tube nor having difficulties feeding with the orogastric tube.

Prenatal diagnosis of middle interhemispheric variant of holoprosencephaly: review of literature and prenatal case series.

OBJECTIVE: Middle interhemispheric (MIH) variant of holoprosencephaly (HPE) or syntelencephaly is a rare prosencephalic cleavage disorder. In literature, few cases of accurate prenatal diagnosis have been reported. We report on four additional prenatally diagnosed cases. METHODS: Between 2012 and 2017, four cases of MIH HPE were retrieved. Data on prenatal imaging, genetic analysis, and pathological investigation are collected. A "PubMed" and "Trip database" search were conducted revealing six papers reporting on 11 prenatally diagnosed cases. RESULTS AND DISCUSSION: Four additional cases of MIH HPE were diagnosed at an earlier gestational age (between 17 and 25 weeks of gestation) compared with 11 cases from the literature review (15-39 weeks). First trimester transvaginal ultrasound facilitates correct differentiation between the severe HPE variants. Frequent association with ZIC2 mutation was found in nearly 50% of the cases (5/11) compared with one case in our series. CONCLUSIONS: MIH variant of HPE is detectable from the early second trimester and should be considered in the differential diagnosis when the cavum septi pellucidi (CSP) is absent. Genetic analysis and autopsy should be conducted to investigate this more recent and rare variant.

Rapid diagnosis of trisomy 13 of maternal origin by quantitative fluorescent polymerase chain reaction analysis in a pregnancy with fetal holoprosencephaly, premaxillary agenesis, postaxial polydactyly of left hand and overriding aorta.

OBJECTIVE: We present rapid diagnosis of trisomy 13 of maternal origin by quantitative fluorescent polymerase chain reaction (QF-PCR) in a pregnancy with multiple fetal abnormalities. CASE REPORT: A 35-year-old, primigravid woman was referred for amniocentesis at 24 weeks of gestation because of multiple congenital anomalies in the fetus. Prenatal ultrasound at 23 weeks of gestation revealed holoprosencephaly, premaxillary agenesis, postaxial polydactyly of the left hand and overriding aorta. Amniocentesis was performed subsequently, and QF-PCR analysis using the polymorphic DNA markers of D13S789 (13q22.3), D13S790 (13q31.1) and D13S767 (13q31.3) on the DNA extracted from uncultured amniocytes and parental bloods showed trisomy 13 of maternal origin. Conventional cytogenetic analysis on the cultured amniocytes confirmed trisomy 13. The pregnancy was subsequently terminated, and a malformed fetus was delivered with multiple anomalies consistent with the prenatal diagnosis. CONCLUSION: QF-PCR analysis is useful for rapid confirmation of trisomy 13 and the parental origin when prenatal ultrasound findings are suspicious of fetal trisomy 13.

Prenatal diagnosis of middle interhemispheric variant of holoprosencephaly: Report of two cases.

Holoprosencephaly ranges in severity based on the degree of anatomic abnormality. Middle interhemispheric variant of holoprosencephaly is a less common and often milder variant that has the characteristic sonographic findings of an absent cavum septum pellucidum and a single fused ventricle. This subtype may be associated with genetic conditions that have not been well-described in the literature. We present two cases of middle interhemispheric variant of holoprosencephaly diagnosed on fetal ultrasound.

First-trimester fetal neurosonography: technique and diagnostic potential.

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.

Fetal Magnetic Resonance Imaging (MRI) in Holoprosencephaly and Associations With Clinical Outcome: Implications for Fetal Counseling.

Holoprosencephaly is the most common malformation of forebrain development and includes a wide spectrum of severity. The objective of this retrospective study was to evaluate fetal magnetic resonance imaging (MRI) associations with outcome. Of the 63 cases identified on antenatal ultrasonography, 28 cases were confirmed on fetal MRI. There were 17 live births; 9 patients died within the first month of life. There were 7 survivors. The vast majority were nonambulatory and required feeding support; none required respiratory support. We found that presence and number of non-holoprosencephaly-associated malformations was also associated with survival. Of 5 patients with 3 or more systemic anomalies, 4 died regardless of holoprosencephaly subtype and 1 was lost to follow-up. Patients with suspected holoprosencephaly on ultrasonography should have full body fetal MRI and echocardiogram to better evaluate systemic anomalies. Counseling should involve pediatric palliative care services to prepare families in caring for babies with limited life span.

A Neonate Born with Holoprosencephaly Sequence of A Gestational Diabetic Mother: A Rare Case.

Holoprosencephaly is a rare spectrum of congenital malformation associated with midline facial defects and absence of olfactory tract. Sequence occurs at 4th to 8th week of gestational age due to failure or incomplete diverticulation and cleavage of primitive prosencephalon. It is most common brain malformation with an incidence 1:250 in conceptuses and associated with a high rate of spontaneous abortion, and prevalence of 1:16000 in live borns. The etiopathogenesis of holoprosencephaly is heterogeneous and multifactorial, may be environmental, metabolic factors or teratogenic including insulin-dependent maternal diabetes, alcohol consumption. In this study, we described a case of holoprosencephaly neonate with 34 weeks gestational age and antenatal ultrasonography diagnosed as congenital defects in the central nervous system, asymmetric growth of head. After birth the infant was presented with multiple congenital anomalies (cleft lip, cleft palate, microphthalmia, absent philtrum, absent nasal septum with single naris) similar to holoprosencephaly sequence.

Aventriculi associated with holoprosencephaly in a dog.

CASE DESCRIPTION: A 10-month-old neutered male mixed breed dog was presented for assessment of poorly controlled seizures. CLINICAL FINDINGS: Magnetic resonance imaging of the brain disclosed complete absence of the lateral and third ventricles and mesencephalic aqueduct. Postmortem computed tomographic (CT) imaging and positive contrast cisterno-ventriculography confirmed the lack of a contiguous ventricular system. However, histopathology identified the presence of vestigial lateral and third ventricles with hypoplastic choroid plexus, atresia of the third ventricle, and fused thalami, consistent with a diagnosis of lobar holoprosencephaly (HPE). CLINICAL RELEVANCE: To our knowledge, this report is the first case of radiographically confirmed aventriculi associated with HPE, a rare congenital malformation previously reported in people, to be described in veterinary medicine.