Peritrigonal and temporo-occipital heterotopia with corpus callosum and cerebellar dysgenesis

Pisano, Tiziana; Barkovich, A. James; Leventer, Richard J.; Squier, Waney; Scheffer, Ingrid E.; Parrini, Elena; Blaser, Susan; Marini, Carla; Robertson, Stephen P.; Tortorella, Gaetano; Rosenow, Felix; Thomas, Pierre; McGillivray, George; Andermann, Eva; Andermann, Frédérick; Berkovic, Samuel F.; Dobyns, William B.; Guerrini, Renzo

doi:10.1212/wnl.0b013e31826aac88

Cited by 37 publications

(28 citation statements)

References 23 publications

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“…7 For further details on EPGP procedures please refer to multiple publications. 6,9,10,11 . Seizure lateralization was based on ictal EEG when available, or interictal EEG and clinical semiology.…”

Section: Methodsmentioning

confidence: 99%

Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy

Fallil

Pardoe

Bachman

et al. 2015

Epilepsy & Behavior

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Purpose Periventricular nodular heterotopia (PVNH) is a malformation of cortical development due to impaired neuronal migration resulting in the formation of nodular masses of neurons and glial cells in close proximity to the ventricular walls. We report the clinical characteristics of the largest case series of FLNA negative patients with seizures and bilateral periventricular heterotopia. Methods Participants were recruited through the Epilepsy Phenome/Genome Project (EPGP), a multicenter collaborative effort to collect detailed phenotypic data and DNA on a large number of individuals with epilepsy, including a cohort with symptomatic epilepsy related to PVNH. Included subjects had epilepsy and MRI confirmed bilateral PVNH. MRI studies were visually and quantitatively reviewed to investigate the topographic extent of PVNH, symmetry and laterality. Key Findings We analyze data on 71 patients with bilateral PVNH. The incidence of febrile seizures was 16.6%. There was at least one other family member with epilepsy in 36.9% of this population. Developmental delay was present in 21.8%. Focal onset seizures were the most common type of seizure presentation (79.3%). High heterotopia burden was strongly associated with female gender and trigonal nodular localization. There was no evidence for differences in brain volume between PVNH subjects and controls. No relationship was observed between heterotopic volume and gender, developmental delay, location of PVNH, ventricular or cerebellar abnormalities, laterality of seizure onset, age at seizure onset and duration of epilepsy. Significance A direct correlation was observed between high heterotopia burden, female gender and trigonal location in this large cohort of FLNA-negative bilateral PVNH patients with epilepsy. Quantitative MRI measurements indicate that this correlation is based on the diffuse nature of the heterotopic nodules rather than on the total volume of abnormal heterotopic tissue.

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Section: Methodsmentioning

confidence: 99%

Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy

Fallil

Pardoe

Bachman

et al. 2015

Epilepsy & Behavior

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“…When the nodules are bilateral and numerous, a genetic basis is probable and other brain malformations are often reported. 18,116,136 …”

Section: Periventricular Nodular Heterotopiamentioning

confidence: 99%

Malformations of cortical development: clinical features and genetic causes

Guerrini

Dobyns

2014

The Lancet Neurology

421

345

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Malformations of cortical development are common causes of developmental delay and epilepsy. Some patients have early, severe neurological impairment, but others have epilepsy or unexpected deficits that are detectable only by screening. The rapid evolution of molecular biology, genetics, and imaging has resulted in a substantial increase in knowledge about the development of the cerebral cortex and the number and types of malformations reported. Genetic studies have identified several genes that might disrupt each of the main stages of cell proliferation and specification, neuronal migration, and late cortical organisation. Many of these malformations are caused by de-novo dominant or X-linked mutations occurring in sporadic cases. Genetic testing needs accurate assessment of imaging features, and familial distribution, if any, and can be straightforward in some disorders but requires a complex diagnostic algorithm in others. Because of substantial genotypic and phenotypic heterogeneity for most of these genes, a comprehensive analysis of clinical, imaging, and genetic data is needed to properly define these disorders. Exome sequencing and high-field MRI are rapidly modifying the classification of these disorders.

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“…Patients with rare autosomal recessive bilateral PNH can have severe congenital microcephaly and thin overlying cortex with abnormal gyri [Sheen et al, 2004]. In the fairly common posterior predominant syndromes, PNH is limited to the trigones, temporal and occipital horns, and can be associated with overlying polymicrogyria, hippocampal and cerebellar hypoplasia, or hydrocephalus [Pisano et al, 2012].…”

Section: Brain Imagingmentioning

confidence: 99%

Genetic Basis of Brain Malformations

et al. 2016

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Malformations of cortical development (MCD) represent a major cause of developmental disabilities, severe epilepsy, and reproductive disadvantage. Genes that have been associated to MCD are mainly involved in cell proliferation and specification, neuronal migration, and late cortical organization. Lissencephaly-pachygyria-severe band heterotopia are diffuse neuronal migration disorders causing severe global neurological impairment. Abnormalities of the LIS1, DCX, ARX, RELN, VLDLR, ACTB, ACTG1, TUBG1, KIF5C, KIF2A, and CDK5 genes have been associated with these malformations. More recent studies have also established a relationship between lissencephaly, with or without associated microcephaly, corpus callosum dysgenesis as well as cerebellar hypoplasia, and at times, a morphological pattern consistent with polymicrogyria with mutations of several genes (TUBA1A, TUBA8, TUBB, TUBB2B, TUBB3, and DYNC1H1), regulating the synthesis and function of microtubule and centrosome key components and hence defined as tubulinopathies. MCD only affecting subsets of neurons, such as mild subcortical band heterotopia and periventricular heterotopia, have been associated with abnormalities of the DCX, FLN1A, and ARFGEF2 genes and cause neurological and cognitive impairment that vary from severe to mild deficits. Polymicrogyria results from abnormal late cortical organization and is inconstantly associated with abnormal neuronal migration. Localized polymicrogyria has been associated with anatomo-specific deficits, including disorders of language and higher cognition. Polymicrogyria is genetically heterogeneous, and only in a small minority of patients, a definite genetic cause has been identified. Megalencephaly with normal cortex or polymicrogyria by MRI imaging, hemimegalencephaly and focal cortical dysplasia can all result from mutations in genes of the PI3K-AKT-mTOR pathway. Postzygotic mutations have been described for most MCD and can be limited to the dysplastic tissue in the less diffuse forms.

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Peritrigonal and temporo-occipital heterotopia with corpus callosum and cerebellar dysgenesis

Cited by 37 publications

References 23 publications

Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy

Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy

Malformations of cortical development: clinical features and genetic causes

Genetic Basis of Brain Malformations

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