Diagnostic Approach to Cerebellar Hypoplasia

Accogli, Andrea; Addour-Boudrahem, Nassima; Srour, Myriam

doi:10.1007/s12311-020-01224-5

Cited by 30 publications

(27 citation statements)

References 157 publications

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“…Although many factors play a role in its etiology, there is no consensus on the terminology, definition and mechanism yet. It may occur as a result of acquired or congenital genetic disorders with different neurodevelopmental outcomes (3,13,14). In this study, the characteristics, management and outcomes of pregnant women diagnosed with prenatal FCM are shown.…”

Section: Discussionmentioning

confidence: 96%

“…Central nervous system malformations are the second most common congenital malformations after cardiac anomalies and constitute one-third of malformations diagnosed in the prenatal period (11,12). Cerebellar malformations (hypoplasia, agenesis) is a term that generally defines the cerebellum as volume loss or embryological failure (13,14). Although many factors play a role in its etiology, there is no consensus on the terminology, definition and mechanism yet.…”

Section: Discussionmentioning

confidence: 99%

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Prenatal characteristics and management of pregnants with fetal cerebellar malformation: 4-year single center experience

KORKMAZ

Alataş²,

AYDIN>

et al. 2022

Anatolian Current Medical Journal

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Introduction: Fetal cerebellar malformations (FCM) are known as very rare central nervous system malformations that occur as hypoplasia or agenesis of the cerebellum or vermis. In this study, the characteristics, diagnostic methods, risk factors and management of pregnant women diagnosed with FCM in the prenatal period were investigated. Material and Method: The patients who diagnosed with prenatal FCM in the perinatology center between March 2017-February 2021 were included, retrospectively. The frequency of fetal magnetic resonance imaging (MRI), amniocentesis and/or karyotype analysis rates, and termination frequency were evaluated. In addition, the factors affecting the amniocentesis and the termination/follow-up decision were investigated. Results: A total of 42 pregnant with FCM were included. The median gestational age was 24.0 years, and the mean gestational week was 25+2 (SD±5+1) weeks. Nearly half (40.5%) of patients were diagnosed before 24 weeks of gestation and 45.2% were primiparous. Cerebellar hypoplasia was observed in 47.6%, while vermis agenesis was observed in almost one third (31.0%); and also 19.0% had multiple FCM. The fetal USG was used in all pregnant women, fetal MRI was performed in only 4.8% for diagnosis of FCM. The rate of amniocentesis and karyotype analysis were 11.9% and 7.1%, retrospectively. No any complications were observed after the amniocentesis. The termination rate was 30.9%. The mean gestational week of those who had live birth was higher than those who were terminated (24+4 vs 20+5) (p=0.019). Conclusion: The frequency of FCM diagnosis has increased with the development of modern medicine and technology. There is no relationship between demographic characteristics of pregnant women and FCM. Socio-economic levels and religious belief differences affect the termination and birth rates.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Prenatal characteristics and management of pregnants with fetal cerebellar malformation: 4-year single center experience

KORKMAZ

Alataş²,

AYDIN>

et al. 2022

Anatolian Current Medical Journal

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“…In contrast, expression of NAV2 in basal ganglia and white matter expression was largely undetectable [8]. Noteworthy, cerebellar cortical dysplasia is also found in a few other NDDs that are frequently autosomal recessive, such as Joubert syndrome and related disorders (JSRDs), Poretti-Boltshauser syndrome, muscular dystrophy (dystroglycanopathies), and Chudley-McCullough syndrome [4,5]. In these conditions, the association with other medical issues and additional brainstem and/or cerebral imaging features may help the differential diagnosis, as presence of hearing loss, callosal agenesis, fronto-mesial polymicrogyria, and intracranial cysts in Chudley-McCullough syndrome or the molar tooth sign and progressive retinal, kidney, and liver disease in JSRDs.…”

Section: Discussionmentioning

confidence: 99%

“…To assess if loss of sick also leads to altered synaptic activity, we performed heat induced seizures by subjecting flies to 42 °C for 30 s [21]. We observed that sick T2A−GAL4 /Df flies exhibit a rapid onset of seizure like behavior (Supplemental material Videos 3,4). Over 75% of sick T2A−GAL4 /Df flies exhibit heat induced seizures and they require about 15 s to recover once returned to room temperature (Fig.…”

Section: Surviving Sick Mutants Show Climbing and Heat-induced Seizuresmentioning

confidence: 98%

“…Acquired or genetic disruptions that impair the complex regulatory machinery of cerebellar development may result in a broad array of diverse congenital anomalies frequently associated with neurodevelopmental disorders (NDDs) [3]. Among these, cerebellar vermis hypoplasia is the most common, often representing a non-specific finding in a large proportion of individuals affected with intellectual disability [4]. In contrast, cerebellar dysplasia is very rare and is often part of a more complex brain malformation [5].…”

Section: Introductionmentioning

confidence: 99%

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Loss of Neuron Navigator 2 Impairs Brain and Cerebellar Development

Accogli

Musante

et al. 2022

Cerebellum

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Cerebellar hypoplasia and dysplasia encompass a group of clinically and genetically heterogeneous disorders frequently associated with neurodevelopmental impairment. The Neuron Navigator 2 (NAV2) gene (MIM: 607,026) encodes a member of the Neuron Navigator protein family, widely expressed within the central nervous system (CNS), and particularly abundant in the developing cerebellum. Evidence across different species supports a pivotal function of NAV2 in cytoskeletal dynamics and neurite outgrowth. Specifically, deficiency of Nav2 in mice leads to cerebellar hypoplasia with abnormal foliation due to impaired axonal outgrowth. However, little is known about the involvement of the NAV2 gene in human disease phenotypes. In this study, we identified a female affected with neurodevelopmental impairment and a complex brain and cardiac malformations in which clinical exome sequencing led to the identification of NAV2 biallelic truncating variants. Through protein expression analysis and cell migration assay in patient-derived fibroblasts, we provide evidence linking NAV2 deficiency to cellular migration deficits. In model organisms, the overall CNS histopathology of the Nav2 hypomorphic mouse revealed developmental anomalies including cerebellar hypoplasia and dysplasia, corpus callosum hypo-dysgenesis, and agenesis of the olfactory bulbs. Lastly, we show that the NAV2 ortholog in Drosophila, sickie (sick) is widely expressed in the fly brain, and sick mutants are mostly lethal with surviving escapers showing neurobehavioral phenotypes. In summary, our results unveil a novel human neurodevelopmental disorder due to genetic loss of NAV2, highlighting a critical conserved role of the NAV2 gene in brain and cerebellar development across species.

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Prenatal diagnosis of pontocerebellar hypoplasia with postnatal follow‐up

Jaillard,

Valence,

Vande Perre

et al. 2024

Prenatal Diagnosis

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ObjectiveTo describe the MR features enabling prenatal diagnosis of pontocerebellar hypoplasia (PCH).MethodThis was a retrospective single monocentre study. The inclusion criteria were decreased cerebellar biometry on dedicated neurosonography and available fetal Magnetic Resonance Imaging (MRI) with PCH diagnosis later confirmed either genetically or clinically on post‐natal MRI or by autopsy. The exclusion criteria were non‐available MRI and sonographic features suggestive of a known genetic or other pathologic diagnosis. The collected data were biometric or morphological imaging parameters, clinical outcome, termination of pregnancy (TOP), pathological findings and genetic analysis (karyotyping, chromosomal microarray, DNA sequencing targeted or exome). PCH was classified as classic, non‐classic, chromosomal, or unknown type.ResultsForty‐two fetuses were diagnosed with PCH, of which 27 were referred for decreased transverse cerebellar diameter at screening ultrasound. Neurosonography and fetal MRI were performed at a mean gestational age of 29 + 4 and 31 + 0 weeks, respectively. Termination of pregnancy occurred. Pregnancy was terminated in 24 cases. Neuropathological examination confirmed the diagnosis in 24 cases and genetic testing identified abnormalities in 29 cases (28 families, 14 chromosomal anomaly). Classic PCH is associated with pontine atrophy and small MR measurements decreasing with advancing gestation.ConclusionThis is the first large series of prenatally diagnosed PCHs. Our study shows the essential contribution of fetal MRI to the prenatal diagnosis of PCH. Classic PCHs are particularly severe and are associated with certain MR features.

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Diagnostic Approach to Cerebellar Hypoplasia

Cited by 30 publications

References 157 publications

Prenatal characteristics and management of pregnants with fetal cerebellar malformation: 4-year single center experience

Prenatal characteristics and management of pregnants with fetal cerebellar malformation: 4-year single center experience

Loss of Neuron Navigator 2 Impairs Brain and Cerebellar Development

Prenatal diagnosis of pontocerebellar hypoplasia with postnatal follow‐up

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