De novo and inherited private variants in MAP1B in periventricular nodular heterotopia

AbstractPathogenic FLNA variants can be identified in patients with seizures accompanied by periventricular nodular heterotopia (PVNH). It is unusual to find FLNA aberrations in epileptic patients without PVNH on brain imaging. We report a boy with cryptogenic West syndrome followed by refractory seizures and psychomotor delay. We performed whole-exome sequencing and identified a de novo missense variant in FLNA. It is noteworthy that this patient showed no PVNH. As no other pathogenic variants were found in epilepsy-related genes, this FLNA variant likely caused West syndrome but with no PVNH.

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A new allelic variant of periventricular nodular heterotopia type 7 in a patient with adrenogenital syndrome due to a 21-hydroxylase deficiency

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2019.06.50-56 ◽

2019 ◽

pp. 50-56

Author(s):

Е.Л. Дадали ◽

Т.В. Маркова ◽

А.О. Боровиков ◽

А.Л. Чухрова ◽

Н.Н. Вассерман ◽

...

Keyword(s):

De Novo ◽

Speech Development ◽

Monogenic Disease ◽

Homozygous Mutation ◽

Hydroxylase Deficiency ◽

Adrenogenital Syndrome ◽

Periventricular Nodular Heterotopia ◽

Monogenic Diseases ◽

Nodular Heterotopia ◽

21 Hydroxylase Deficiency

Представлено описание клинико-генетических характеристик ребенка 2 лет с двумя моногенными заболеваниями: сольтеряющей формой адрено--генитального синдрома с аутосомно-рецессивным типом наследования и узловой гетеротопий мозга 7 типа, наследующейся аутосомно-доминантно, диагностированных с использованием двух различных молекулярно-генетических методов. Наличие адрено-генитального синдрома диагностировано в первые дни жизни на основании типичных клинических проявлений и подтверждено путём прямой ДНК-диагностики, в результате которой обнаружена гомозиготная мутация p.R356W в гене CYP21А2. Наличие второго моногенного заболевания предполагалось на основании диагностики грубой задержки психомоторного и речевого развития и аномалий строения головного мозга, обнаруженных при проведении магнитно-резонансной томографии. При секвенировании клинического экзома выявлена ранее не описанная нуклеотидная замена с.2015С>T (р.W672I) в гене NEDD4L. Патогенные варианты в домене HECT данного белка приводят к перивентрикулярной узловой гетеротопии 7 типа (OMIM:617021). Анализ данного варианта методом прямого секвенирования по Сэнгеру в семье показал его происхождение de novo. We report 2-year-old girl with two monogenic diseases - adrenogenital syndrome with autosomal recessive inheritance mode and periventricular nodular heterotopia type 7 with autosomal dominant, diagnosed by two different molecular genetic methods. The presence of adreno-genital syndrome diagnosed in the first days of life based on typical clinical manifestations and the homozygous mutation was detected p.R356Wby direct DNA testing CYP21А2 gene. The presence of the second monogenic disease was proposed base on the observation the severe delay of psychomotor and speech development and abnormalities of the brain structure detected by MRI. Clinical exome sequencing identified previously not described single nucleotide substitution c.2015С>T (p.W672I) in NEDD4L gene. Pathogenic variants in HECT domain of this protein lead to periventricular nodular heterotopia type 7 (OMIM:617021). Analysis of segregation this variant in the family by direct sequencing of Sanger showed its origin de novo.

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Compound heterozygous variants in LAMC3 in association with posterior periventricular nodular heterotopia

BMC Medical Genomics ◽

10.1186/s12920-021-00911-4 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Carla De Angelis ◽

Alicia B. Byrne ◽

Rebecca Morrow ◽

Jinghua Feng ◽

Thuong Ha ◽

...

Keyword(s):

Cortical Development ◽

Occipital Cortex ◽

Compound Heterozygous ◽

Valuable Insight ◽

Periventricular Nodular Heterotopia ◽

Case Presentation ◽

Malformation Of Cortical Development ◽

Nodular Heterotopia ◽

Compound Heterozygous Variants ◽

Insight Into

Abstract Background Periventricular nodular heterotopia (PNH) is a malformation of cortical development characterized by nodules of abnormally migrated neurons. The cause of posteriorly placed PNH is not well characterised and we present a case that provides insights into the cause of posterior PNH. Case presentation We report a fetus with extensive posterior PNH in association with biallelic variants in LAMC3. LAMC3 mutations have previously been shown to cause polymicrogyria and pachygyria in the occipital cortex, but not PNH. The occipital location of PNH in our case and the proposed function of LAMC3 in cortical development suggest that the identified LAMC3 variants may be causal of PNH in this fetus. Conclusion We hypothesise that this finding extends the cortical phenotype associated with LAMC3 and provides valuable insight into genetic cause of posterior PNH.

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27. EEG-fMRI of nodule-cortex interaction during interictal spiking in periventricular nodular heterotopia

Journal of Clinical Neuroscience ◽

10.1016/j.jocn.2009.07.052 ◽

2009 ◽

Vol 16 (11) ◽

pp. 1533-1534

Author(s):

JS Archer ◽

DF Abbott ◽

R Masterton ◽

S Palmer ◽

GD Jackson

Keyword(s):

Periventricular Nodular Heterotopia ◽

Nodular Heterotopia

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Electroencephalographic Recordings of Focal Seizures in Patients Affected by Periventricular Nodular Heterotopia: Role of the Heterotopic Nodules in the Genesis of Epileptic Discharges

Journal of Child Neurology ◽

10.1177/08830738040190031701 ◽

2004 ◽

Vol 19 (3) ◽

pp. 369-377

Author(s):

Giorgio Battaglia ◽

Silvana Franceschetti ◽

Luisa Chiapparini ◽

Elena Freri ◽

Stefania Bassanini ◽

...

Keyword(s):

Brain Regions ◽

Periventricular Nodular Heterotopia ◽

Focal Seizures ◽

Ictal Eeg ◽

Epileptic Discharges ◽

Nodular Heterotopia ◽

Eeg Recordings ◽

Drug Resistant Epilepsy ◽

Video Eeg

Patients affected by periventricular nodular heterotopia are frequently characterized by focal drug-resistant epilepsy. To investigate the role of periventricular nodules in the genesis of seizures, we analyzed the electroencephalographic (EEG) features of focal seizures recorded by means of video-EEG in 10 patients affected by different types of periventricular nodular heterotopia and followed for prolonged periods of time at the epilepsy center of our institute. The ictal EEG recordings with surface electrodes revealed common features in all patients: all seizures originated from the brain regions where the periventricular nodular heterotopia were located; EEG patterns recorded on the leads exploring the periventricular nodular heterotopia were very similar both at the onset and immediately after the seizure's end in all patients. Our data suggest that seizures are generated by abnormal anatomic circuitries, including the heterotopic nodules and adjacent cortical areas. The major role of heterotopic neurons in the genesis and propagation of epileptic discharges must be taken into account when planning surgery for epilepsy in patients with periventricular nodular heterotopia. ( J Child Neurol 2005;20:369—377).

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