Mathieu Milh

Aix-Marseille Université, Marsiglia, Provence-Alpes-Côte d'Azur, France

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Publications (95)275.1 Total impact

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    ABSTRACT: Variants in the WD repeat 45 (WDR45) gene in human Xp11.23 have recently been identified in patients suffering from neurodegeneration with brain iron accumulation, a genetically and phenotypically heterogeneous condition. WDR45 variants cause a childhood-onset encephalopathy accompanied by neurodegeneration in adulthood and iron accumulation in the basal ganglia. They have been almost exclusively found in females, and male lethality was suggested. Here we describe a male patient suffering from a severe and early neurological phenotype, initially presenting early-onset epileptic spasms in clusters associated with an abnormal interictal electroencephalography showing slow background activity, large amplitude asynchronous spikes and abnormal neurological development. This patient is a carrier of a 19.9-kb microdeletion in Xp11.23 containing three genes, including WDR45. These findings reveal that males with WDR45 deletions are viable, and can present with early-onset epileptic encephalopathy without brain iron accumulation.European Journal of Human Genetics advance online publication, 15 July 2015; doi:10.1038/ejhg.2015.159.
    European journal of human genetics: EJHG 07/2015; DOI:10.1038/ejhg.2015.159 · 4.23 Impact Factor
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    ABSTRACT: Mutations in the KCNQ2 gene encoding the voltage-dependent potassium M channel Kv7.2 subunit cause either benign epilepsy or early onset epileptic encephalopathy (EOEE). It has been proposed that the disease severity rests on the inhibitory impact of mutations on M current density. Here, we have analyzed the phenotype of 7 patients carrying the p.A294V mutation located on the S6 segment of the Kv7.2 pore domain (Kv7.2(A294V)). We investigated the functional and subcellular consequences of this mutation and compared it to another mutation (Kv7.2(A294G)) associated with a benign epilepsy and affecting the same residue. We report that all the patients carrying the p.A294V mutation presented the clinical and EEG characteristics of EOEE. In CHO cells, the total expression of Kv7.2(A294V) alone, assessed by western blotting, was only 20% compared to wild-type. No measurable current was recorded in CHO cells expressing Kv7.2(A294V) channel alone. Although the total Kv7.2(A294V) expression was rescued to wild-type levels in cells co-expressing the Kv7.3 subunit, the global current density was still reduced by 83% compared to wild-type heteromeric channel. In a configuration mimicking the patients' heterozygous genotype i.e. Kv7.2(A294V)/Kv7.2/Kv7.3, the global current density was reduced by 30%. In contrast to Kv7.2(A294V), the current density of homomeric Kv7.2(A294G) was not significantly changed compared to wild-type Kv7.2. However, the current density of Kv7.2(A294G)/Kv7.2/Kv7.3 and Kv7.2(A294G)/Kv7.3 channels were reduced by 30% and 50% respectively, compared to wild-type Kv7.2/Kv7.3. In neurons, the p.A294V mutation induced a mislocalization of heteromeric mutant channels to the somato-dendritic compartment, while the p.A294G mutation did not affect the localization of the heteromeric channels to the axon initial segment. We conclude that this position is a hotspot of mutation that can give rise to a severe or a benign epilepsy. The p.A294V mutation does not exert a dominant-negative effect on wild-type subunits but alters the preferential axonal targeting of heteromeric Kv7 channels. Our data suggest that the disease severity is not necessarily a consequence of a strong inhibition of M current and that additional mechanisms such as abnormal subcellular distribution of Kv7 channels could be determinant. Copyright © 2015. Published by Elsevier Inc.
    Neurobiology of Disease 05/2015; 80. DOI:10.1016/j.nbd.2015.04.017 · 5.20 Impact Factor
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    ABSTRACT: Mutations in the KCNQ2 gene, encoding a potassium channel subunit, were reported in patients presenting epileptic phenotypes of varying severity. Patients affected by benign familial neonatal epilepsy (BFNE) are at the milder end of the spectrum, they are affected by early onset epilepsy but their subsequent neurological development is usually normal. Mutations causing BFNE are often inherited from affected parents. Early infantile epileptic encephalopathy type 7 (EIEE7) is at the other end of the severity spectrum and, although EIEE7 patients have early onset epilepsy too, their neurological development is impaired and they will present motor and intellectual deficiency. EIEE7 mutations occur de novo. Electrophysiological experiments suggested a correlation between the type of mutation and the severity of the disease but intra and interfamilial heterogeneity exist. Here, we describe the identification of KCNQ2 mutation carriers who had children affected with a severe epileptic phenotype, and found that these individuals were mosaic for the KCNQ2 mutation. These findings have important consequences for genetic counseling and indicate that neurological development can be normal in the presence of somatic mosaicism for a KCNQ2 mutation. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 05/2015; DOI:10.1002/ajmg.a.37152 · 2.05 Impact Factor
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    ABSTRACT: In a large family of Algerian origin, we aimed to identify the genetic mutation segregating with simultaneous presence of adult-onset, paucisymptomatic, slowly progressive, cerebellar ataxia in 7 adults and congenital ataxia in 1 child, and then to assess the involvement of GRID2 mutations in 144 patients with congenital cerebellar ataxia. We used a combined approach of linkage analysis and whole-exome sequencing in one family, and a targeted gene panel sequencing approach in 144 congenital ataxias. In the large family with spinocerebellar ataxia, we identified a missense mutation (c.1966C>G/p.Leu656Val) in the GRID2 gene, in a heterozygous state in adults, and in a homozygous state in one child with congenital ataxia, compatible with a semidominant transmission pattern. In 144 patients affected with congenital ataxia, we identified 2 missense de novo GRID2 mutations in 2 children (c.1960G>A/p.Ala654Thr, c.1961C>A/p.Ala654Asp). They affect the same amino acid as the previously described Lurcher mutation in mice; the variant in the large family concerns a nearby amino acid. In humans, GRID2 had only been involved in ataxia through complete loss-of-function mutations due to exon deletions. We report the first point mutations in this gene, with putative gain-of-function mechanisms, and a semidominant transmission as was observed in the Lurcher mice model. Of note, cerebellar ataxia is the core phenotype, but with variable severity ranging from very mild adult-onset to congenital-onset ataxias linked to both the heterozygous and homozygous state of the variant, and the position of the mutation. © 2015 American Academy of Neurology.
    Neurology 04/2015; 84(17). DOI:10.1212/WNL.0000000000001524 · 8.30 Impact Factor
  • C Barraud · A Cano · C Boulay · M Milh · G Bollini · B Chabrol
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    ABSTRACT: Vitamin D deficiency rickets remains a public health issue in many parts of the world. In France, this diagnosis has almost disappeared since 1992 with routine vitamin D supplementation for children. Therefore, it is more difficult for doctors to identify risk factors and early signs of this disease. In this article, we report a rickets diagnosis acquired by vitamin D deficiency in a child who presented with the onset of a genu valgum and difficulty walking at the age of 9½ years. This patient was a Comorian child followed up from his birth for Dorfman-Chanarin syndrome. Dorfman-Chanarin syndrome is a rare disease, with about 80 cases reported in the literature. It belongs to the group of neutral lipid storage diseases (NLSD) characterized especially on the skin by ichthyosis. This child presented risk factors for vitamin D deficiency (dark skin color, prolonged and exclusive breastfeeding, premature end of supplementation, and particularly severe ichthyosis) that should have alerted us to the risk of vitamin D deficiency and the need for supplementation. This case highlights the importance of vitamin D, especially if there are risk factors such as ichthyosis, and the need to remain watchful in monitoring all chronic diseases. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
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    ABSTRACT: Mutations in the TBC1D24 gene were first reported in an Italian family with a unique epileptic phenotype consisting of drug-responsive, early-onset idiopathic myoclonic seizures. Patients presented with isolated bilateral or focal myoclonia, which could evolve to long-lasting attacks without loss of consciousness, with a peculiar reflex component, and were associated with generalized tonic-clonic seizures. This entity was named "familial infantile myoclonic epilepsy" (FIME). More recently, TBC1D24 mutations have been shown to cause a variable range of disorders, including epilepsy of various seizure types and severity, non-syndromic deafness, and DOORS syndrome. We report on the electro-clinical features of two brothers, born to first-cousin parents, affected with infantile-onset myoclonic epilepsy. The peculiar epileptic presentation prompted us to perform direct sequencing of the TBC1D24 gene. The patients had very early onset of focal myoclonic fits with variable topography, lasting a few minutes to several hours, without loss of consciousness, which frequently evolved to generalized myoclonus or myoclonic status. Reflex myoclonia were noticed in one patient. Neurological outcome was marked by moderate intellectual disability. Despite the high frequency of seizures, repeated EEG recordings showed normal background rhythm and rare interictal spikes and waves. We found a homozygous missense mutation, c.457G>A/p.Glu153Lys, in the two affected brothers. This observation combined with recent data from the literature, suggest that mutations in TBCD24 cause a pathological continuum, with FIME at the "benign" end and severe drug-refractory epileptic encephalopathy on the severe end. Early-onset myoclonic epilepsy with focal and generalized myoclonic seizures is a common characteristic of this continuum. Copyright © 2015 Elsevier B.V. All rights reserved.
    Epilepsy Research 03/2015; 111:72-77. DOI:10.1016/j.eplepsyres.2015.01.008 · 2.19 Impact Factor
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    ABSTRACT: Heterozygous dominant mutations of PRRT2 have been associated with various types of paroxysmal neurological manifestations, including benign familial infantile convulsions and paroxysmal kinesigenic dyskinesia. The phenotype associated with biallelic mutations is not well understood as few cases have been reported. PRRT2 screening was performed by Sanger sequencing and quantitative multiplex PCR of short fluorescent fragments. A CGH array was used to characterise the size of the deletion at the 16p11.2 locus. Five patients with homozygous or compound heterozygous deleterious PRRT2 gene mutations are described. These patients differ from those with a single mutation by their overall increased severity: (1) the combination of at least three different forms of paroxysmal neurological disorders within the same patient and persistence of paroxysmal attacks; (2) the occurrence of uncommon prolonged episodes of ataxia; and (3) the association of permanent neurological disorders including learning difficulties in four patients and cerebellar atrophy in 2. Our observations expand the phenotype related to PRRT2 insufficiency, and highlight the complexity of the phenotype associated with biallelic mutations, which represents a severe neurological disease with various paroxysmal disorders and frequent developmental disabilities. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Journal of Neurology Neurosurgery & Psychiatry 01/2015; 86(7). DOI:10.1136/jnnp-2014-309025 · 5.58 Impact Factor
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    ABSTRACT: PTEN gene (MIM 601628) is a tumor suppressor gene implicated in PTEN hamartoma tumor syndromes (PHTS) including Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, and Proteus-like syndrome. Bannayan-Riley-Ruvalcaba syndrome is considered as the pediatric form of PHTS. More recently, children presenting autism spectrum disorders with macrocephaly (ASD-M) have been reported. We report clinical data from seven patients diagnosed in childhood with a PTEN germline mutation, excluding cases of familial Cowden syndrome. This study underlines the variability of phenotype associated with PTEN mutations diagnosed at pediatric age. Most of the patients did not fulfill usual criteria of Bannayan-Riley-Ruvalcaba syndrome or ASD-M. PTEN testing should be considered in any child presenting with severe macrocephaly (>+4SD) and another feature of PHTS. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 12/2014; 19(2). DOI:10.1016/j.ejpn.2014.11.012 · 1.93 Impact Factor
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    ABSTRACT: The pathophysiological mechanisms of epileptic spasms are still poorly understood. The role of subcortical structures has been suggested on the basis of non-localized EEG features and from experimental data. The description of asymmetric spasms associated with lateralized EEG patterns has challenged this view and raises the possibility of a cortical origin. This study investigated the cortical organization of partial seizures associated with epileptic spasms in children undergoing intracerebral EEG recordings for presurgical evaluation. Eleven children with drug resistant epileptic spasms and for whom depth electrode recordings were performed were retrospectively studied. In all children several features suggested a focal origin. Cortical involvement was studied using the "Epileptogenicity Index" (EI). A focal origin was finally demonstrated in 10/11 patients. Seven patients demonstrated pre-ictal changes in the seizure onset zone area. EI analysis showed maximal values in the temporal (n=5), parietal (n=1) or frontal (n=5) cortices. EEG changes were also observed in the premotor cortex during spasms in patients with frontal or parietal seizures and in 3/5 patients with temporal lobe seizures. Good surgical outcome (class I or II) was obtained in 7/10 patients. Seizures associated with epileptic spasms may originate from various cortical regions. Premotor/motor cortices are probably involved in determining ictal clinical changes.
    Epilepsy Research 08/2014; 108(9). DOI:10.1016/j.eplepsyres.2014.08.008 · 2.19 Impact Factor
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    ABSTRACT: Tuberous sclerosis complex (TSC), caused by dominant mutations in either TSC1 or TSC2 tumour suppressor genes is characterized by the presence of brain malformations, the cortical tubers that are thought to contribute to the generation of pharmacoresistant epilepsy. Here we report that tuberless heterozygote Tsc1+/− mice show functional upregulation of cortical GluN2C-containing N-methyl-D-aspartate receptors (NMDARs) in an mTOR-dependent manner and exhibit recurrent, unprovoked seizures during early postnatal life (<P19). Seizures are generated intracortically in the granular layer of the neocortex. Slow kinetics of aberrant GluN2C-mediated currents in spiny stellate cells promotes excessive temporal integration of persistent NMDAR-mediated recurrent excitation and seizure generation. Accordingly, specific GluN2C/D antagonists block seizures in Tsc1+/− mice in vivo and in vitro. Likewise, GluN2C expression is upregulated in TSC human surgical resections, and a GluN2C/D antagonist reduces paroxysmal hyperexcitability. Thus, GluN2C receptor constitutes a promising molecular target to treat epilepsy in TSC patients.
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    ABSTRACT: Tuberous sclerosis complex (TSC), caused by dominant mutations in either TSC1 or TSC2 tumour suppressor genes is characterized by the presence of brain malformations, the cortical tubers that are thought to contribute to the generation of pharmacoresistant epilepsy. Here we report that tuberless heterozygote Tsc1+/− mice show functional upregulation of cortical GluN2C-containing N-methyl-D-aspartate receptors (NMDARs) in an mTOR-dependent manner and exhibit recurrent, unprovoked seizures during early postnatal life (<P19). Seizures are generated intracortically in the granular layer of the neocortex. Slow kinetics of aberrant GluN2C-mediated currents in spiny stellate cells promotes excessive temporal integration of persistent NMDAR-mediated recurrent excitation and seizure generation. Accordingly, specific GluN2C/D antagonists block seizures in Tsc1+/− mice in vivo and in vitro. Likewise, GluN2C expression is upregulated in TSC human surgical resections, and a GluN2C/D antagonist reduces paroxysmal hyperexcitability. Thus, GluN2C receptor constitutes a promising molecular target to treat epilepsy in TSC patients.
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    [Show abstract] [Hide abstract]
    ABSTRACT: Tuberous sclerosis complex (TSC), caused by dominant mutations in either TSC1 or TSC2 tumour suppressor genes is characterized by the presence of brain malformations, the cortical tubers that are thought to contribute to the generation of pharmacoresistant epilepsy. Here we report that tuberless heterozygote Tsc1+/− mice show functional upregulation of cortical GluN2C-containing N-methyl-D-aspartate receptors (NMDARs) in an mTOR-dependent manner and exhibit recurrent, unprovoked seizures during early postnatal life (<P19). Seizures are generated intracortically in the granular layer of the neocortex. Slow kinetics of aberrant GluN2C-mediated currents in spiny stellate cells promotes excessive temporal integration of persistent NMDAR-mediated recurrent excitation and seizure generation. Accordingly, specific GluN2C/D antagonists block seizures in Tsc1+/− mice in vivo and in vitro. Likewise, GluN2C expression is upregulated in TSC human surgical resections, and a GluN2C/D antagonist reduces paroxysmal hyperexcitability. Thus, GluN2C receptor constitutes a promising molecular target to treat epilepsy in TSC patients.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tuberous sclerosis complex (TSC), caused by dominant mutations in either TSC1 or TSC2 tumour suppressor genes is characterized by the presence of brain malformations, the cortical tubers that are thought to contribute to the generation of pharmacoresistant epilepsy. Here we report that tuberless heterozygote Tsc1+/− mice show functional upregulation of cortical GluN2C-containing N-methyl-D-aspartate receptors (NMDARs) in an mTOR-dependent manner and exhibit recurrent, unprovoked seizures during early postnatal life (<P19). Seizures are generated intracortically in the granular layer of the neocortex. Slow kinetics of aberrant GluN2C-mediated currents in spiny stellate cells promotes excessive temporal integration of persistent NMDAR-mediated recurrent excitation and seizure generation. Accordingly, specific GluN2C/D antagonists block seizures in Tsc1+/− mice in vivo and in vitro. Likewise, GluN2C expression is upregulated in TSC human surgical resections, and a GluN2C/D antagonist reduces paroxysmal hyperexcitability. Thus, GluN2C receptor constitutes a promising molecular target to treat epilepsy in TSC patients.
    Nature Communications 08/2014; DOI:10.1038/ncomms5563 · 10.74 Impact Factor
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    ABSTRACT: High-resolution array comparative genomic hybridization (a-CGH) enables the detection of intragenic rearrangements, such as single exon deletion or duplication. This approach can lead to the identification of new disease genes. We report on the analysis of 54 male patients presenting with intellectual deficiency (ID) and a family history suggesting X-linked (XL) inheritance or maternal skewed X-chromosome inactivation (XCI), using a home-made X-chromosome-specific microarray covering the whole human X-chromosome at high resolution. The majority of patients had whole genome array-CGH prior to the selection and we did not include large rearrangements such as MECP2 and FMR1 duplications. We identified four rearrangements considered as causative or potentially pathogenic, corresponding to a detection rate of 8%. Two CNVs affected known XLID genes and were therefore considered as causative (IL1RAPL1 and OPHN1 intragenic deletions). Two new CNVs were considered as potentially pathogenic as they affected interesting candidates for ID. The first CNV is a deletion of the first exon of the TRPC5 gene, encoding a cation channel implicated in dendrite growth and patterning, in a child presenting with ID and an autism spectrum disorder (ASD). The second CNV is a partial deletion of KLHL15, in a patient with severe ID, epilepsy, and anomalies of cortical development. In both cases, in spite of strong arguments for clinical relevance, we were not able at this stage to confirm pathogenicity of the mutations, and the causality of the variants identified in XLID remains to be confirmed. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 08/2014; 164(8). DOI:10.1002/ajmg.a.36602 · 2.05 Impact Factor
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    ABSTRACT: Epileptic encephalopathy (EE) refers to a clinically and genetically heterogeneous group of severe disorders characterized by seizures, abnormal interictal electro-encephalogram, psychomotor delay, and/or cognitive deterioration. We ascertained two multiplex families (including one consanguineous family) consistent with an autosomal-recessive inheritance pattern of EE. All seven affected individuals developed subclinical seizures as early as the first day of life, severe epileptic disease, and profound developmental delay with no facial dysmorphism. Given the similarity in clinical presentation in the two families, we hypothesized that the observed phenotype was due to mutations in the same gene, and we performed exome sequencing in three affected individuals. Analysis of rare variants in genes consistent with an autosomal-recessive mode of inheritance led to identification of mutations in SLC13A5, which encodes the cytoplasmic sodium-dependent citrate carrier, notably expressed in neurons. Disease association was confirmed by cosegregation analysis in additional family members. Screening of 68 additional unrelated individuals with early-onset epileptic encephalopathy for SLC13A5 mutations led to identification of one additional subject with compound heterozygous mutations of SLC13A5 and a similar clinical presentation as the index subjects. Mutations affected key residues for sodium binding, which is critical for citrate transport. These findings underline the value of careful clinical characterization for genetic investigations in highly heterogeneous conditions such as EE and further highlight the role of citrate metabolism in epilepsy.
    The American Journal of Human Genetics 07/2014; 95(1):113-20. DOI:10.1016/j.ajhg.2014.06.006 · 10.99 Impact Factor
  • B. Chabrol · C. Boulay · M. Milh
    Archives de Pédiatrie 05/2014; 21(5):284-285. DOI:10.1016/S0929-693X(14)71570-2 · 0.41 Impact Factor
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    ABSTRACT: In order to assess the cognitive and adaptive profiles of school-aged patients with Dravet syndrome (DS), we proposed to evaluate the intelligence and adaptive scores in twenty-one 6- to 10-year-old patients with DS followed in our institution between 1997 and 2013. Fourteen patients were tested using the Wechsler Intelligence Scale for Children (WISC) and the Vineland Adaptive Behavioral Scales (VABS); 6 patients could not be tested with the WISC and were tested with the VABS only, and one was tested with the WISC only. Data regarding the epilepsy were retrospectively collected. Statistical analysis (Spearman rank order and Pearson correlation coefficient) was used to correlate early epilepsy characteristics with the cognitive and adaptive scores.
    Epilepsy & Behavior 01/2014; 31C:143-148. DOI:10.1016/j.yebeh.2013.11.021 · 2.06 Impact Factor
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    ABSTRACT: Mutations in the KCNQ2 and KCNQ3 genes encoding for Kv 7.2 (KCNQ2; Q2) and Kv 7.3 (KCNQ3; Q3) voltage-dependent K(+) channel subunits, respectively, cause neonatal epilepsies with wide phenotypic heterogeneity. In addition to benign familial neonatal epilepsy (BFNE), KCNQ2 mutations have been recently found in families with one or more family members with a severe outcome, including drug-resistant seizures with psychomotor retardation, EEG suppression-burst pattern (Ohtahara syndrome) and distinct neuroradiological features, a condition that was named "KCNQ2 encephalopathy". In the present paper, we describe clinical, genetic and functional data from 17 patients/families whose electro-clinical presentation was consistent with the diagnosis of BFNE. Sixteen different heterozygous mutations were found in KCNQ2, including 10 substitutions, three ins/del and three large deletions. One substitution was found in KCNQ3. Most of these mutations were novel, except for four KCNQ2 substitutions that were shown to be recurrent. Electrophysiological studies in mammalian cells revealed that homomeric or heteromeric KCNQ2 and/or KCNQ3 channels carrying mutant subunits with newly-found substitutions displayed reduced current densities. In addition, we describe, for the first time, that some mutations impair channel regulation by syntaxin-1A, highlighting a novel pathogenetic mechanism for KCNQ2-related epilepsies. This article is protected by copyright. All rights reserved.
    Human Mutation 12/2013; 35(3). DOI:10.1002/humu.22500 · 5.05 Impact Factor
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    ABSTRACT: Acute necrotizing encephalopathy is a rare neurologic disease most often triggered by a febrile viral event affecting an otherwise healthy infant. The clinical course is characterized by rapid deterioration of the neurological condition that often leads to coma and requires intensive care. The diagnosis is usually suggested by MRI, which shows symmetrical and focal necrotic lesions of thalami. Acute necrotizing encephalopathy has been linked in recent studies to an autosomal-dominant mutation of the gene for the protein RAN-binding protein 2. We report three cases in siblings of Tunisian origin. Two of them presented with acute necrotizing encephalopathy at the age of 9 months in the immediate aftermath of a viral infection. The molecular study conducted in the family showed that both patients and their mother were carriers of the missense mutation gene RAN-binding protein 2. Although the role of Ran BP2 protein is incompletely known, mutation of the RANBP2 gene causes rare, reversible central neurologic disorders. Suspected diagnosis is facilitated by MRI, which shows specific lesions of multifocal, symmetric involvement of the thalami, brainstem tegmentum, supratentorial white matter, and cerebellum. Due to the low frequency of the disease and its non-specific clinical presentation, the diagnosis of acute necrotizing encephalopathy is a major challenge, while preventative measures can be proposed in familial mutation.
    Archives de Pédiatrie 12/2013; · 0.41 Impact Factor

Publication Stats

964 Citations
275.10 Total Impact Points

Institutions

  • 2010–2015
    • Aix-Marseille Université
      • Faculté des Sciences
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2008–2014
    • Assistance Publique Hôpitaux de Marseille
      • • Service de neurophysiologie clinique
      • • Service de pédiatrie et oncologie pédiatrique
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2013
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • Institut de Génomique Fonctionnelle,
      Montpelhièr, Languedoc-Roussillon, France
  • 2010–2013
    • Hôpital Européen, Marseille
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2009
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
    • Polytech Marseille
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2005
    • Hungarian Academy of Sciences
      • MTA Institute of Experimental Medicine
      Budapest, Budapest fovaros, Hungary