NDE1-related disorders: A recurrent NDE1 pathogenic variant causing Lissencephaly 4 can also be associated with microhydranencephaly.

NudE Neurodevelopment Protein 1 (NDE1) gene encodes a protein required for microtubule organization, mitosis, and neuronal migration. Biallelic pathogenic variants of NDE1 gene are associated with structural central nervous system abnormalities, specifically microlissencephaly and microhydranencephaly. The root of these different phenotypes remains unclear. Here, we report a 20-year-old male patient referred to our clinics due to severe microcephaly, developmental delay, spastic quadriplegia, and dysmorphic features. The cranial computed tomography revealed abnormal brain structure and excess of cerebrospinal fluid, consistent with microhydranencephaly. A homozygous c.684_685del, p.(Pro229TrpfsTer85) change in NDE1 gene was found by clinical exome analysis. The variant has previously been reported in individuals with microlissencephaly, therefore we propose that the same variant within the gene may cause either microlissencephaly or microhydranencephaly phenotypes. There are only a few papers about NDE1-related disorders in the literature and the patient we described is important to clarify the phenotypic spectrum of the disease.

Hydranencephaly: Clinical Features and Survivorship in a Retrospective Cohort.

OBJECTIVE: Hydranencephaly is a congenital central nervous system disorder characterized by the complete or near-complete absence of the cerebral cortex and basal ganglia. Because of its rarity, data on the clinical features and survivorship remain sparse. We aim to determine the clinical features and survivorship of a cohort of patients with hydranencephaly. METHODS: We performed a retrospective cohort study of all patients diagnosed with hydranencephaly at our institution from 2008 to 2018. Data on demographics, clinical features, presence of comorbidities, surgical operations performed, and status on last follow-up were collected. Survival curves were generated using Kaplan-Meier analysis. RESULTS: Fifty patients were included in the cohort, who had a median age at diagnosis of 4 months and a female predilection. The most common clinical manifestations were macrocephaly (92%) and seizures or myoclonic movements. Infection was present in 36% of cases, endocrinopathies in 22%, dysmorphisms in 20%, and cardiac disease in 8%. Twenty patients underwent shunt insertion, with half developing a postoperative complication at a mean follow-up of 14.9 months. The median survival of the cohort was not reached at 7.5 years. Among the patients with follow-up, characteristics were similar between the surgical and nonsurgical groups, except for the greater incidence of infections in the nonsurgical group. The survival curves among the groups were significantly different, with a hazard ratio of 3.731 in the nonsurgical group. CONCLUSIONS: In this large single-center retrospective cohort of patients with hydranencephaly, novel findings are presented regarding the clinical manifestations and survivorship of this condition.

Phenotypic spectrum of NDE1-related disorders: from microlissencephaly to microhydranencephaly.

Biallelic variants in the NDE1 gene have been shown to occur in extreme microcephaly. Most of the patients displayed microlissencephaly but one with microhydranencephaly. We report on three sibs in which the brain MRI and CT scans demonstrated variable degree of reduced volume of cerebral hemispheres and ventriculomegaly. Further, they had agenesis of corpus callosum, cerebellar, and brainstem hypoplasia. Fetal ultrasound at 32 weeks' gestation of the third sib revealed severe micrencephaly with extensive hydranencephaly and an anomaly consistent with non cleaved (fused) thalami. Because of the fused thalami, the STIL gene was targeted initially but showed negative results. His postnatal MRI showed that the cerebral hemispheres are markedly reduced in size (with no definite frontal, parietal, or occipital lobes) and replaced by a large sac filled with CSF. An intact falx cerebri was identified. This extensive hydarencephaly led us to consider the NDE1 and to identify a novel homozygous nonsense variant (c.54G>A, p.W18*). The variability of the degree of brain malformations and the apparent fusion of the thalami were illusive and delayed the recognition of the genetic etiology. Our results provide the first antenatal description of this rare syndrome. Further, we expand the genetic architecture and the neuroradiologic phenotype of NDE1-related disorders.

Bilateral population receptive fields in congenital hemihydranencephaly.

PURPOSE: Congenital hemihydranencephaly (HH) is a very rare disorder characterised by prenatal near-complete unilateral loss of the cerebral cortex. We investigated a patient affected by congenital right HH whose visual field extended significantly into the both visual hemifields, suggesting a reorganisation of the remaining left visual hemisphere. We examined the early visual cortex reorganisation using functional MRI (7T) and population receptive field (pRF) modelling. METHODS: Data were acquired by means of a 7T MRI while the patient affected by HH viewed conventional population receptive field mapping stimuli. Two possible pRF reorganisation schemes were evaluated: where every cortical location processed information from either (i) a single region of the visual field or (ii) from two bilateral regions of the visual field. RESULTS: In the patient affected by HH, bilateral pRFs in single cortical locations of the remaining hemisphere were found. In addition, using this specific pRF reorganisation scheme, the biologically known relationship between pRF size and eccentricity was found. CONCLUSIONS: Bilateral pRFs were found in the remaining left hemisphere of the patient affected by HH, indicating reorganisation of intra-cortical wiring of the early visual cortex and confirming brain plasticity and reorganisation after an early cerebral damage in humans.

Mutations in FLVCR2 associated with Fowler syndrome and survival beyond infancy.

Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH, OMIM 225790), also known as Fowler syndrome, is a rare autosomal recessive disorder, caused by mutations in FLVCR2. Hallmarks of the syndrome are glomerular vasculopathy in the central nervous system, severe hydrocephaly, hypokinesia and arthrogryphosis. The disorder is considered prenatally lethal. We report the first patients, a brother and a sister, with Fowler syndrome and survival beyond infancy. The patients present a phenotype of severe intellectual and neurologic disability with seizures, absence of functional movements, and no means of communication. Imaging of the brain showed calcifications, profound ventriculomegaly with only a thin edging of the cerebral cortex and hypoplastic cerebellum. Investigation with whole-exome sequencing (WES) revealed, in both patients, a homozygous pathogenic mutation in FLVCR2, c.1289C>T, compatible with a diagnosis of Fowler syndrome. The results highlight the power of combining WES with a thorough clinical examination in order to identify disease-causing mutations in patients whose clinical presentation differs from previously described cases. Specifically, the findings demonstrate that Fowler syndrome is a diagnosis to consider, not only prenatally but also in severely affected children with gross ventriculomegaly on brain imaging.

Hydranencephaly: cerebral spinal fluid instead of cerebral mantles.

The authors report a wide and updated revision of hydranencephaly, including a literature review, and present the case of a patient affected by this condition, still alive at 36 months.Hydranencephaly is an isolated and with a severe prognosis abnormality, affecting the cerebral mantle. In this condition, the cerebral hemispheres are completely or almost completely absent and are replaced by a membranous sac filled with cerebrospinal fluid. Midbrain is usually not involved. Hydranencephaly is a relatively rare cerebral disorder. Differential diagnosis is mainly relevant when considering severe hydrocephalus, poroencephalic cyst and alobar holoprosencephaly. Ethical questions related to the correct criteria for the surgical treatment are also discussed.

[Prenatal diagnosis of central nervous system malformations]. / A központi idegrendszer fejlodési rendellenességeinek praenatalis diagnosztikája.

The prenatal diagnosis of fetal malformations have been the subject of numerous publications in the literature. This has dramatically increased in the last 15 years, mainly due to the advent of high-resolution ultrasound. In addition adequate guidelines issued by professional organizations have encouraged the universal approach to the imaging of fetal anatomy as well as malformations. One of the most significant groups of the fetal anomalies is the central nervous system malformation. Due to its prevalence and severity the praenatal diagnostics of central nervous system malformations got basic significance. In this review we attempted to summarize the recent informations concerning the prenatal diagnostics of the central nervous system anomalies.

Hemihydranencephaly: living with half brain dysfunction.

Hemi-hydranencephaly is a very rare condition characterized by complete or almost near-complete unilateral absence of the cortical cortex, which is filled by a sac of cerebrospinal fluid. Prenatal vascular disruption with occlusion of the carotid artery territories ipsilateral to the damaged brain is the presumed pathogenesis.We have selected nine cases that fit the clinical and pathologic characteristics of hemi-hydranencephaly, demonstrating that destruction of one hemisphere may be not always associated with severe neurologic impairment and may allow an almost normal life. This disorder is an example of a possible prenatal re-organization in which the right and left cerebral hemispheres present functional potentiality to make up the damaged brain.The cases reported in the literature are discussed, including a patient previously reported and followed-up for 10 years. A review of the cases is performed with an evaluation of the most important aspect of this rare and mysterious disorder.

Endoscopic choroid plexus coagulation in infants with hydranencephaly or hydrocephalus with a minimal cortical mantle.

BACKGROUND/AIMS: This study evaluates endoscopic choroid plexus coagulation, in conjunction with third ventriculostomy when technically feasible, as a strategy to treat patients with hydranencephaly or hydrocephalus with a minimal cortical mantle. METHODS: We retrospectively reviewed patients with hydranencephaly (n = 4) or hydrocephalus with the cortical mantle <1 cm in maximal thickness (n = 4) who underwent endoscopic choroid plexus coagulation from 2007 to 2010. Endoscopic third ventriculostomy was performed simultaneously when technically feasible (in 3 of 8 patients). Endoscopic management was considered successful if a shunt was not subsequently required. RESULTS: Endoscopic management was successful in 4 of 8 patients (50%) who did not require a shunt over a median follow-up period of 15 months (range 2.5-24). Four patients (50%) failed endoscopic management and required a shunt 1 month to 11 weeks after endoscopic surgery. One patient died 4 days after shunt placement due to pneumonia and renal failure. Three of 4 patients who had a successful endoscopic procedure ultimately died of causes that were likely unrelated to hydrocephalus (pneumonia in 2 patients and sudden infant death syndrome in 1 patient). Besides failure to control hydrocephalus adequately in 4 patients, there were no additional complications noted after endoscopic surgeries. CONCLUSION: Endoscopic choroid plexus coagulation can enable some infants with hydranencephaly or massive hydrocephalus to avoid a ventriculoperitoneal shunt.

Porencephaly and hydranencephaly in six dogs.

A retrospective study was performed to identify dogs with cerebrospinal fluid-filled cavitatory lesions on MRI. Six dogs were included and the lesions were classified. In the three dogs in the present study with hydranencephaly, unilateral but complete loss of the temporal and parietal lobes was noted and had almost complete loss of the occipital and frontal lobes of a cerebral hemisphere. In the three dogs with porencephaly, there was unilateral incomplete loss of the parietal lobe and one dog had additional partial loss of the temporal and frontal lobes. Two of the dogs with porencephaly had seizures; the third showed no associated clinical signs. The dogs with hydranencephaly had mentation changes and circled compulsively. The two porencephalic dogs with seizures were treated with phenobarbitone. One of the dogs with hydranencephaly showed increased frequency and duration of circling; one dog's clinical signs did not progress and the third dog was euthanased due to increasing aggression. The dog with increased circling had ventriculoperitoneal shunt placement and the circling frequency reduced.

Hidranencefalia en un recién nacido por toxoplasmosis congénita / Hydroanencephalia in a newborn due to congenital toxoplasmosis

A case is described of a full-term newborn with hydroanencephalia due to congenital toxoplasmosis. Prenatal diagnosis had been made. The infection was supposedly acquired in the early stages of the pregnancy, the mother presented positive serology for active infection. The newborn presented elevated specific IgM. Fetal and newborn MRI was compatible with hydrancencephalia. The newborn presented macrocephalia, cataracts, abnormal archaic reflexes, hypotonia, thermoregulation abnormalities, and altered spinal fluid. Due to the severity and rarity of this clinical picture, and an absence of a national detection program, the possibility of offering mothers the possibility of detecting this illness is highlighted.

Se presenta el caso de un recién nacido de término con hidranencefalia por toxoplasmosis congénita con diagnóstico prenatal, el cual habría adquirido su infección en forma precoz durante el embarazo. Destaca madre con serología positiva para infección activa. Recién Nacido (RN) con IgM específica elevada. Resonancia Magnética fetal y del neonato compatible con hidranencefalia. RN con macrocefalia, catarata, reflejos arcaicos anormales, hipotonía, alteración del la termorregulación y LCR alterado. Frente a la gravedad y lo inusual del cuadro clínico y considerando la ausencia de un programa nacional de tamizaje se destaca la importancia de ofrecer a la madre embarazada la posibilidad de detección precoz y prevención de esta enfermedad frente a las severas complicaciones neurológicas de esta infección congénita.

Hemihydranencephaly syndrome: case report and review.

BACKGROUND: Hemihydranencephaly (HHDNC) is a rare disorder with complete or almost complete unilateral absence of cerebral cortex. METHODS: This study describes a 27 months-old girl presenting with developmental delay and generalized weakness more on the left side. Bilateral blindness was noted since the age of 6 months. RESULTS: Her fundus examination revealed bilateral optic atrophy, dilated tortuous retinal veins with increased intra-ocular tension. She had polyuria and recurrent attacks of dehydration due to neurogenic diabetes insipidus. Her blood protein S was deficient. Her magnetic resonance imaging (MRI) demonstrated HHDNC with nearly complete absence of the right cerebral hemisphere. Her MR-Arteriography demonstrated total occlusion of right middle and anterior cerebral arteries and attenuated and beaded right posterior cerebral artery. Diffusion tensor MR imaging revealed complete absence of right cortico-spinal and optic tracts with deficient left sided tracts. CONCLUSION: In contrast to the good outcome of the few reported cases of HHDNC, this case had severe global disabilities.

Hidranencefalia: caso clínico / Hydranencephaly: a clinical case

La hidranencefalia pertenece a las encefalopatías del sistema nervioso central. Es un defecto grave de la perfusión cerebral que produce una destrucción tardía de los territorios irrigados por ambas arterias carótidas internas, con preservación de los territorios irrigados por las arterias vertebro basilares. El conocimiento de esta encefalopatía por el odontopediatra permitirá tratar adecuadamente al paciente y realizar un tratamiento exitoso, mejorando su calidad de vida. Se presenta el caso clínico de un niño al que durante el quinto mes de vida intrauterina le fue realizada una ecografía donde se diagnosticó la encefalopatía.

Hydranencephaly associated with cerebellar involvement and bilateral microphthalmia and colobomas.

Hydranencephaly is an encephaloclastic central nervous system disorder characterised by severe destruction of the cerebral hemispheres with preservation of posterior fossa structures. We present MRI and neurosonography features of a unique case of hydranencephaly involving cerebellum (in the form of complete liquefaction of cerebellar hemispheres) and cerebral hemispheres with associated bilateral microphthalmia and ocular colobomas. This is an exceptional case as to the best to our knowledge. In humans, such a severe involvement of cerebellum has not been reported in cases of hydranencephaly. It is essential to distinguish hydranencephaly from gross hydrocephalus, as treatment and prognosis of the two are totally different. During differentiation, it is important to remember that severe cerebellar involvement can be seen in hydranencephaly.

Hemihydranencephaly: rare disease with key to secrets of the brain.

A 21-year-old male presented to us in status epilepticus. On investigation, he was found to have an extremely rare disorder called 'hemihydranencephaly'. Review of literature revealed that hemihydranencephaly was not always incompatible with life and that research into this disorder would help in understanding the development, functioning, untapped potential and reorganisation capacity of the brain.