Middle Interhemispheric Variant Of Holoprosencephaly Research Articles

EP27.07: Middle interhemispheric variant of holoprosencephaly associated with bilateral ectrodactyly:probably Hartsfield syndrome?

EP27.07: Middle interhemispheric variant of holoprosencephaly associated with bilateral ectrodactyly:probably Hartsfield syndrome?

The diagnosis of the middle interhemispheric variant of holoprosencephaly with fetal MRI

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.

Sonographic Diagnosis of the Middle Interhemispheric Variant of Holoprosencephaly in the Prenatal Period

Holoprosencephaly is a disorder of development and separation of prosencephalic vesicles. There are 3 main types of holoprosencephaly: alobar, semilobar, and lobar. A rare form of the disease, middle interhemispheric variant (MIHV), or syntelencephaly, is a generally milder variant characterized by the absence of the cavum septum pellucidum and a single fused ventricle. Etiology is multifactorial and most cases are sporadic. However, the disease has also been associated with teratogenic exposure, intrauterine infections, maternal metabolic diseases, genetic disorders such as chromosomal aneuploidies and single gene disorders. Our aim is to share the characteristics of our case with MIH variant, which was reported very rarely in the prenatal period, and to compare it with other cases in the literature.

VP27.03: Middle interhemispheric variant of holoprosencephaly: prenatal case series and review of literature

VP27.03: Middle interhemispheric variant of holoprosencephaly: prenatal case series and review of literature

Postnatal ultrasound diagnosis of middle interhemispheric variant of holoprosencephaly in a newborn with Edwards syndrome

A case of postnatal ultrasound diagnosis the middle interhemispheric variant of holoprosencephaly in a newborn with Edwards syndrome is presented. The characteristic postnatal ultrasound signs of this variant of holoprosencephaly and signs of magnetic resonance imaging of this pathology according to literary sources are presented.

A de novo variant in RAC3 causes severe global developmental delay and a middle interhemispheric variant of holoprosencephaly.

RAC3 is a member of the Rho GTPases family, which has important regulatory functions in aspects of neuronal morphogenesis. Rho GTPases show a conformational change in two regions (switch I and II) through GTP binding, which provides a platform for selective interactions with functionally diverse proteins. Missense variants in the switch I and II regions of RAC3 were recently suggested to cause severe intellectual disability and brain malformations. Here, we report an individual with a novel de novo RAC3 variant (c.101 C>G, p.(Pro34Arg)), which substitutes for an evolutionarily conserved amino acid within the switch I region. The patient showed severe global developmental delay, intellectual disability, epilepsy, and laryngeal dystonia. An imaging study revealed characteristic brain dysplasia, including coexistence of the middle interhemispheric variant of holoprosencephaly and brainstem dysmorphism. Our study supports that RAC3 variants cause syndromic neurodevelopmental disorders and brain structural abnormality, and expands the phenotypic spectrum of RAC3-related disorders.

Case 236: Middle Interhemispheric Variant of Holoprosencephaly.

History A 13-year-old girl presented for evaluation and further management of spastic diplegia cerebral palsy. Absence of the corpus callosum was noted at screening prenatal head ultrasonography. She was born at full term via spontaneous vaginal delivery. Physical examination revealed decreased axial muscle tone and increased muscle tone in her extremities; the latter was more severe. She was nonambulatory. No midline craniofacial anomaly was seen. She had dysarthria but was able to speak in full sentences. She was in sixth grade with an individualized education program. She had mild behavioral problems, such as "acting out" in school. Brain magnetic resonance (MR) imaging, including three-dimensional T1- and T2-weighted sequences, was performed without intravenous administration of contrast material to evaluate the brain.

Adult with Middle Interhemispheric Variant of Holoprosencephaly: Neuropsychological, Clinical, and Radiological Findings

The middle interhemispheric variant of holoprosencephaly (MIHV) is a mild, rare variant of holoprosencephaly. Only a few cases of children with MIHV have been reported. Here we report in detail an adult case. The patient is a female in her 30s. The patient underwent an extensive neuropsychological examination, a neurological examination and a magnetic resonance imaging. Neuroradiologically, the patient had a typical finding of MIHV, with the absence of the central corpus callosum and union of posterior frontal and anterior parietal gyri. In neuropsychological examination, the patient had average or above average performance in verbal comprehension, naming, reading and writing, and below average performance in perceptual reasoning, visuospatial abilities, processing speed and memory. Also difficulties in mathematical abilities, psychomotor skills, and executive functions were found. No gross neurological involvement was noted. She was diagnosed with atypical depression, post-traumatic stress disorder and a dissociative disorder in early adulthood. Despite cognitive deficits, she was able to achieve a tertiary level education. This is the first adult case of MIHV described in detail. Our case emphasizes the possibility of a missed diagnosis of marked brain malformations in patients with craniofacial abnormalities. More cases and prospective follow-up studies are needed to understand the evolvement of both neuropsychological and psychiatric symptoms in these patients.

The middle interhemispheric variant of holoprosencephaly: magnetic resonance and diffusion tensor imaging findings.

The middle interhemispheric (MIH) variant of holoprosencephaly (HPE) is the incomplete separation of midline cerebral hemispheres with the absence of callosal body. We aimed to describe the additional knowledge of diffusion tensor imaging (DTI) over conventional MRI in the evaluation of patients with MIH variant of HPE. Conventional MRI and DTI data of five patients were retrospectively evaluated. The parenchymal anomalies as well as changes at white matter tracts were systematically reviewed. Except the callosal body and central cingulum fibres, which were missing in all patients, all other major white matter tracts (superior and inferior longitudinal, superior and inferior fronto-occipital, subcallosal and uncinate fasciculi and anterior commissure) had a normal course, thickness and integrity on diffusion tensor images. The genial and splenial callosal fibres were altered and rarefied on tractography. All patients had a central ventricular notch extending into the non-cleaved heterotopic grey matter involving the body of the corpus callosum, which is very typical for the MIH variant of HPE. The remnant traversing white matter fibres above the non-cleaved heterotopic grey matter and incomplete partition of the interhemispheric fissure were also identified. No Probst bundles were detected. A single common ventricle without the septum pellucidum was noted in all patients. One patient had incomplete partition of the thalami, and two patients had abnormally oriented thalami without any prominent interthalamic connection. Vertically oriented hippocampi were detected in four out of five patients. Three patients had relatively flat and vertically oriented Sylvian fissures and in two patients, fissures were abnormally connected over the vertex. Additional DTI findings can not only clearly reveal the white matter alterations better than conventional MRI but also provide a better understanding of the aetiological changes that cause the MIH variant of HPE. DTI can provide a better analysis of cerebral white matter connectivity and promotes understanding of the underlying microstructural changes that occur in patients with the MIH variant of HPE.

Monozygotic twins with de novo ZIC2 gene mutations discordant for the type of holoprosencephaly.

Middle interhemispheric variant of holoprosencephaly (MIH) is a rare brain malformation; hemispheric fusion does not occur at the rostral forebrain, but rather across the posterior frontal region. Barkovich and Quint1 first described and proposed MIH as part of the holoprosencephaly (HPE) spectrum in 1993. Although classic HPE and MIH share several similarities, they are related to different embryological mechanisms: classic HPE is caused by a defect in the formation of the embryonic floor plate, whereas MIH occurs after a disturbance to the roof plate formation.2 The gene ZIC2 is important for the differentiation of the roof plate in the dorsal midline of the neural tube of the developing embryo. In humans, ZIC2 mutations have been identified in 3%–4% of HPE cases, including individuals with MIH, thus confirming that MIH is a variant of HPE.3

Diffusion Tensor Imaging and Fiber Tractography in Syntelencephaly

Syntelencephaly or the middle interhemispheric variant of holoprosencephaly is a rare subtype of holoprosencephaly and consists of a nonseparation of the posterior frontal and parietal regions of both cerebral hemispheres. We report conventional MR imaging, diffusion tensor imaging, and fiber tractography findings of a girl with syntelencephaly and discuss the information that diffusion tensor imaging and fiber tractography may add to conventional MR imaging in this rare brain malformation.

EYA4, deleted in a case with middle interhemispheric variant of holoprosencephaly, interacts withSIX3both physically and functionally

Holoprosencephaly (HPE) is the most common congenital malformation of the developing human forebrain, in which the two cerebral hemispheres fail to separate to various degrees. Although pathological mutations have been identified in up to nine genes, a number of other genes as well as environmental factors are likely to be involved in HPE. Here, we describe a case with the middle interhemispheric variant, a milder variant of HPE, carrying a deletion of approximately 10.4 Mb at 6q22.31-q23.2, which includes the EYA4 gene. EYA4 is one of four vertebrate orthologs of the Drosophila melanogaster gene, eyes absent. EYA4 was co-immunoprecipitated with SIX3, the product of one of the known HPE genes. Moreover, the EYA4 protein was observed to be recruited to the nucleus by the nuclear protein SIX3 under a confocal microscope. EYA4 is a transcriptional coactivator, and was shown to cooperate with transcription factor SIX3 by reporter gene assays. These results demonstrate physical and functional association between EYA4 and SIX3, suggesting that EYA4 is a novel candidate gene of HPE, whose haploinsufficiency leads to HPE through the compromised function of SIX3.

Middle interhemispheric variant of holoprosencephaly associated with bilateral perisylvian polymicrogyria

Pediatrics InternationalVolume 50, Issue 2 p. 241-244 Middle interhemispheric variant of holoprosencephaly associated with bilateral perisylvian polymicrogyria Mehmet H. Atalar, Corresponding Author Mehmet H. Atalar Departments of 1Radiology and 2Pediatrics, Division of Pediatric Neurology, Cumhuriyet University School of Medicine, Sivas and 3Department of Radiology, Ege University School of Medicine, Izmir, TurkeyMehmet H. Atalar, MD, Department of Radiology, Cumhuriyet University School of Medicine, 58140 Sivas, Turkey. Email: [email protected]Search for more papers by this author 1 Dilara Icagasioglu, Dilara Icagasioglu Departments of 1Radiology and 2Pediatrics, Division of Pediatric Neurology, Cumhuriyet University School of Medicine, Sivas and 3Department of Radiology, Ege University School of Medicine, Izmir, TurkeySearch for more papers by this author 2 R. Nuri Sener, R. Nuri Sener Departments of 1Radiology and 2Pediatrics, Division of Pediatric Neurology, Cumhuriyet University School of Medicine, Sivas and 3Department of Radiology, Ege University School of Medicine, Izmir, TurkeySearch for more papers by this author 3 Mehmet H. Atalar, Corresponding Author Mehmet H. Atalar Departments of 1Radiology and 2Pediatrics, Division of Pediatric Neurology, Cumhuriyet University School of Medicine, Sivas and 3Department of Radiology, Ege University School of Medicine, Izmir, TurkeyMehmet H. Atalar, MD, Department of Radiology, Cumhuriyet University School of Medicine, 58140 Sivas, Turkey. Email: [email protected]Search for more papers by this author 1 Dilara Icagasioglu, Dilara Icagasioglu Departments of 1Radiology and 2Pediatrics, Division of Pediatric Neurology, Cumhuriyet University School of Medicine, Sivas and 3Department of Radiology, Ege University School of Medicine, Izmir, TurkeySearch for more papers by this author 2 R. Nuri Sener, R. Nuri Sener Departments of 1Radiology and 2Pediatrics, Division of Pediatric Neurology, Cumhuriyet University School of Medicine, Sivas and 3Department of Radiology, Ege University School of Medicine, Izmir, TurkeySearch for more papers by this author 3 First published: 17 March 2008 https://doi.org/10.1111/j.1442-200X.2007.02311.xCitations: 6Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume50, Issue2April 2008Pages 241-244 RelatedInformation

Syntelencephaly or MIH, a New Variant of Holoprosencephaly

We studied a case of middle interhemispheric variant of holoprosencephaly by magnetic resonance. A five-year-old child presented a mild language delay and relational disorders. The etiopathogenesis of the disorder remains controversial, the two main hypotheses being teratogenic and genetic. Magnetic resonance disclosed typical alterations (abnormal midline connection of cerebral hemispheres in the posterior frontal and parietal regions, partial agenesis of corpus callosum, absence of septum pellucidum) which allowed differential diagnosis from the other types of holoprosencephaly, namely the more typical alobar, semilobar and lobar variants.

Endocrine Disorders Associated with Holoprosencephaly

To investigate the incidence of endocrinopathies in holoprosencephaly (HPE) and correlate the severity of the endocrinopathies with the neuroanatomic abnormalities. We reviewed the histories and medical records of 117 children with HPE for endocrinopathies and related treatments. Neuroimaging studies were graded for severity of HPE, hypothalamus non-separation, and pituitary abnormalities. Diabetes insipidus (DI) occurred in 70% of patients with classic HPE. The severity of the DI correlated with the grade of HPE and hypothalamic non-separation (p < 0.0001). Anterior pituitary dysfunctions were much less common. Hypothyroidism was identified in 11% of patients, hypocorticism in 7%, and growth hormone deficiency in 5%. Only one patient with middle interhemispheric variant of holoprosencephaly (MIH) had any of these disorders. Patients with HPE have a high incidence of DI that may be related to the failure of cleavage of hypothalamic nuclei. Anterior pituitary dysfunctions are much less common than DI.

Middle interhemispheric variant of holoprosencephaly: A very mild clinical case

Middle interhemispheric variant (MIH) of holoprosencephaly or syntelencephaly was described in 19931 as a fourth subtype of holoprosencephaly (HPE), in addition to the three classic types of alobar, semilobar, and lobar HPE.2 MIH consists of an abnormal midline continuity of the posterior frontal and parietal regions of the cerebral hemispheres, with separation of the basal forebrain, anterior frontal lobes, and occipital regions. Although MIH and classic HPE share a number of similarities, they are related to different embryologic mechanisms. Classic HPE is caused by a defect in the formation of the embryonic floor plate, whereas MIH is secondary to a disturbance of formation of the roof plate.3 The ZIC2 gene plays a critical role in differentiation of the roof plate of the developing embryo in the dorsal midline of the neural tube.3 In mice, decreased levels of ZIC2 result in the failure to form midline CNS structures. In humans, mutations in the ZIC2 gene have been found in ∼3 to 4% of HPE cases, including individuals with MIH, confirming that MIH is a variant of HPE.4 …