Publications by authors named "Cecilia Altuzarra"

Article Synopsis
  • Spinal muscular atrophy type 1 (SMA1) is a severe genetic disease affecting motor neurons, and onasemnogene abeparvovec gene transfer therapy (GT) has significantly impacted its treatment, although real-world data is limited.
  • A study in France identified 95 SMA1 patients between June 2019 and June 2022, focusing on 29 who received GT and had over a year of follow-up.
  • Results indicated positive motor development and maintenance of respiratory and feeding functions in treated infants, although many developed spinal deformities, and two patients sadly passed away shortly after treatment.
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We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel Nav1.6, with the aim of describing clinical phenotypes related to functional effects. Six different clinical subgroups were identified: Group 1, benign familial infantile epilepsy (n = 15, normal cognition, treatable seizures); Group 2, intermediate epilepsy (n = 33, mild intellectual disability, partially pharmaco-responsive); Group 3, developmental and epileptic encephalopathy (n = 177, severe intellectual disability, majority pharmaco-resistant); Group 4, generalized epilepsy (n = 20, mild to moderate intellectual disability, frequently with absence seizures); Group 5, unclassifiable epilepsy (n = 127); and Group 6, neurodevelopmental disorder without epilepsy (n = 20, mild to moderate intellectual disability).

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Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disease resulting from mutations in the NTRK1 gene encoding the neurotrophic tyrosine kinase-1 receptor. In this multicenter observational retrospective study, we investigated CIPA patients identified from French laboratories sequencing the NTRK1 gene, and seven patients were identified. Patients originated from France (2), Suriname (2), Mali (1), Kazakhstan (1), and Algeria (1).

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Variants in KCNT1, encoding a sodium-gated potassium channel (subfamily T member 1), have been associated with a spectrum of epilepsies and neurodevelopmental disorders. These range from familial autosomal dominant or sporadic sleep-related hypermotor epilepsy to epilepsy of infancy with migrating focal seizures (EIMFS) and include developmental and epileptic encephalopathies. This study aims to provide a comprehensive overview of the phenotypic and genotypic spectrum of KCNT1 mutation-related epileptic disorders in 248 individuals, including 66 previously unpublished and 182 published cases, the largest cohort reported so far.

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CACNA1A pathogenic mutations are involved in various neurological phenotypes including episodic ataxia (EA2), spinocerebellar ataxia (SCA6), and familial hemiplegic migraine (FHM1). Epilepsy is poorly documented. We studied 18 patients (10 males) carrying de novo or inherited CACNA1A mutations, with median age of 2,5 years at epilepsy onset.

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Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord. Nusinersen has been covered by public healthcare in France since May 2017. The aim of this article is to report results after 1 year of treatment with intrathecal nusinersen in children with SMA types 1 and 2 in France.

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Ataxia-telangiectasia (A-T) is a recessive disorder caused by biallelic pathogenic variants of ataxia-telangiectasia mutated (ATM). This disease is characterized by progressive ataxia, telangiectasia, immune deficiency, predisposition to malignancies, and radiosensitivity. However, hypomorphic variants may be discovered associated with very atypical phenotypes, raising the importance of evaluating their pathogenic effects.

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Objective: To describe the mode of onset of SCN8A-related severe epilepsy in order to facilitate early recognition, and eventually early treatment with sodium channel blockers.

Methods: We reviewed the phenotype of patients carrying a mutation in the SCN8A gene, among a multicentric cohort of 638 patients prospectively followed by several pediatric neurologists. We focused on the way clinicians made the diagnosis of epileptic encephalopathy, the very first symptoms, electroencephalography (EEG) findings, and seizure types.

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Objective: The aim of this study was to expand the spectrum of epilepsy syndromes related to , encoding the presynaptic protein syntaxin-1B, and establish genotype-phenotype correlations by identifying further disease-related variants.

Methods: We used next-generation sequencing in the framework of research projects and diagnostic testing. Clinical data and EEGs were reviewed, including already published cases.

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Objective: Mutations in the syntaxin binding protein 1 gene (STXBP1) have been associated mostly with early onset epileptic encephalopathies (EOEEs) and Ohtahara syndrome, with a mutation detection rate of approximately 10%, depending on the criteria of selection of patients. The aim of this study was to retrospectively describe clinical and electroencephalography (EEG) features associated with STXBP1-related epilepsies to orient molecular screening.

Methods: We screened STXBP1 in a cohort of 284 patients with epilepsy associated with a developmental delay/intellectual disability and brain magnetic resonance imaging (MRI) without any obvious structural abnormality.

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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.

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Background: Early onset epileptic encephalopathies (EOEEs) are dramatic heterogeneous conditions in which aetiology, seizures and/or interictal EEG have a negative impact on neurological development. Several genes have been associated with EOEE and a molecular diagnosis workup is challenging since similar phenotypes are associated with mutations in different genes and since mutations in one given gene can be associated with very different phenotypes. Recently, de novo mutations in KCNQ2, have been found in about 10% of EOEE patients.

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Multiple-respiratory-chain deficiency represents an important cause of mitochondrial disorders. Hitherto, however, mutations in genes involved in mtDNA maintenance and translation machinery only account for a fraction of cases. Exome sequencing in two siblings, born to consanguineous parents, with severe encephalomyopathy, choreoathetotic movements, and combined respiratory-chain defects allowed us to identify a homozygous PNPT1 missense mutation (c.

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Background: Non-progressive congenital ataxias (NPCA) with or without intellectual disability (ID) are clinically and genetically heterogeneous conditions. As a consequence, the identification of the genes responsible for these phenotypes remained limited.

Objective: Identification of a new gene responsible for NPCA and ID.

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Fumarase deficiency (FD), caused by biallelic alteration of the Fumarase Hydratase gene (FH), and a rare metabolic disorder that affects the Krebs cycle, causes severe neurological impairment and fumaric aciduria. Less than 30 unrelated cases are known to date. In addition, heterozygous mutations of the FH gene are responsible for hereditary leiomyomatosis and renal cell cancer (HLRCC).

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Autosomal recessive LPIN1 mutations have been recently described as a novel cause of rhabdomyolysis in a few families. The purpose of the study was to evaluate the prevalence of LPIN1 mutations in patients exhibiting severe episodes of rhabdomyolysis in infancy. After exclusion of primary fatty acid oxidation disorders, LPIN1 coding sequence was determined in genomic DNA and cDNA.

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To assess the efficacy and tolerability of steroids in epileptic syndromes with continuous spike-waves during slow-wave sleep (CSWS), charts of 44 children (25 boys) who received corticosteroids for cognitive and/or behavioral deterioration associated with CSWS were retrospectively reviewed. Awake and sleep electroencephalography (EEG) records, clinical and neuropsychological assessments were available before, during, and after corticosteroid therapy. Evaluation focused on effects on EEG, behavior, and cognition.

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