Publications by authors named "Dana Craiu"

Predicting and quantifying phenotypic consequences of genetic variants in rare disorders is a major challenge, particularly pertinent for 'actionable' genes such as thyroid hormone transporter MCT8 (encoded by the X-linked SLC16A2 gene), where loss-of-function (LoF) variants cause a rare neurodevelopmental and (treatable) metabolic disorder in males. The combination of deep phenotyping data with functional and computational tests and with outcomes in population cohorts, enabled us to: (i) identify the genetic aetiology of divergent clinical phenotypes of MCT8 deficiency with genotype-phenotype relationships present across survival and 24 out of 32 disease features; (ii) demonstrate a mild phenocopy in ~400,000 individuals with common genetic variants in MCT8; (iii) assess therapeutic effectiveness, which did not differ among LoF-categories; (iv) advance structural insights in normal and mutated MCT8 by delineating seven critical functional domains; (v) create a pathogenicity-severity MCT8 variant classifier that accurately predicted pathogenicity (AUC:0.91) and severity (AUC:0.

View Article and Find Full Text PDF

Background And Objectives: Heterozygous variants in RAR-related orphan receptor B () have recently been associated with susceptibility to idiopathic generalized epilepsy. However, few reports have been published so far describing pathogenic variants of this gene in patients with epilepsy and intellectual disability (ID). In this study, we aimed to delineate the epilepsy phenotype associated with pathogenic variants and to provide arguments in favor of the pathogenicity of variants.

View Article and Find Full Text PDF

Introduction: Tuberous sclerosis complex (TSC) is a rare autosomal dominant condition characterized by cutaneous, cerebral, and other multiorgan involvement. Aneurysms due to TSC pathogenic mechanism are rarely present, mainly aortic, renal, or intracranial and very few associated with peripheral circulation. A TSC patient, aged 31 years, who developed brachial and subclavian arteries aneurysms is presented.

View Article and Find Full Text PDF

Brain heterotopia is a group of rare malformations with a heterogeneous phenotype, ranging from asymptomatic to a severe clinical picture (drug-resistant epilepsy, severe developmental delay). The etiology is multifactorial, including both genetic and environmental factors. In the present study, a cohort of 15 pediatric patients with brain heterotopia were investigated by clinical examination, electroencephalographic studies, brain imaging, and genomic tests.

View Article and Find Full Text PDF

Introduction: The aim of this paper is to review the current situation of vaccine hesitancy, with emphasis on children with neurological disorders, and to present the role social media plays in this situation.

Methods: A literature review using the following search words was performed: vaccine∗ OR immune∗ AND hesitancy OR confidence AND social media.

Results: The search retrieved 277 results; 17 duplicates and 234 irrelevant articles were excluded.

View Article and Find Full Text PDF

Introduction: The evidence relating vaccination to febrile seizures and epilepsy is evaluated with an emphasis on febrile seizures (FS), Dravet syndrome (DS), West syndrome, and other developmental and epileptic encephalopathies.

Methods: A systematic literature review using search words vaccination/immunization AND febrile seizures/epilepsy/Dravet/epileptic encephalopathy/developmental encephalopathy was performed. The role of vaccination as the cause/trigger/aggravation factor for FS or epilepsies and preventive measures were analyzed.

View Article and Find Full Text PDF
Article Synopsis
  • * A study evaluated the long-term effects of the T3 analogue Triac on 67 MCT8-deficient patients over a median period of 2.2 years, showing significant reductions in serum T3 levels and improvements in body weight, heart rate, and certain biochemical markers.
  • * The results indicate that Triac effectively reduced key symptoms in MCT8 deficiency without severe adverse events, demonstrating its potential as a treatment option in this patient population.
View Article and Find Full Text PDF
Article Synopsis
  • The article reviews how vaccinations may impact autoimmune disorders of the central nervous system (CNS), specifically focusing on conditions like narcolepsy, anti-NMDAR encephalitis, Rasmussen encephalitis, and febrile infection-related epilepsy syndrome (FIRES).
  • It also explores the relationship between immune-mediated epilepsies and these autoimmune CNS disorders, providing insights on how vaccinations could affect these patients.
  • The review includes considerations of when vaccinations are advisable and when they should be avoided in individuals with these specific autoimmune conditions.
View Article and Find Full Text PDF

Objective: Clinical care of rare and complex epilepsies is challenging, because evidence-based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies.

View Article and Find Full Text PDF

Tuberous sclerosis complex (TSC) is a genetic multisystem disease due to the mutation in one of the two genes TSC1 and TSC2, affecting several organs and systems and carrying a significant risk of early onset and refractory seizures. The pathogenesis of this complex disorder is now well known, with most of TSC-related manifestations being a consequence of the overactivation of the mammalian Target of Rapamycin (mTOR) complex. The discovery of this underlying mechanism paved the way for the use of a class of drugs called mTOR inhibitors including rapamycin and everolimus and specifically targeting this pathway.

View Article and Find Full Text PDF

Dravet Syndrome (DS) is burdened by high epilepsy-related premature mortality due to status epilepticus (SE). We surveyed centres within Europe through the Dravet Italia Onlus and EpiCARE network (European Reference Network for Rare and Complex Epilepsies). We collated responses on seven DS SCN1A+ patients who died following refractory SE (mean age 6.

View Article and Find Full Text PDF

Objective: Autosomal recessive pathogenic variants of the SLC13A5 gene are associated with severe neonatal epilepsy, developmental delay, and tooth hypoplasia/hypodontia. We report on 14 additional patients and compare their phenotypic features to previously published patients to identify the clinical hallmarks of this disorder.

Methods: We collected clinical features of 14 patients carrying biallelic variants in SLC13A5 and performed a PubMed search to identify previously published patients.

View Article and Find Full Text PDF

Background: Paediatric Neurology (PN) is a discipline focused on diagnosis, comprehensive management and research into diseases of the central and peripheral nervous system from fetal life to transition into adulthood. The European Paediatric Neurology Society first designed and published the European PN training programme in the European Paediatric Neurology Syllabus in 2002. This was important in gaining recognition for the sub-specialty from the European Academy of Paediatrics and the European Academy of Neurology and in 2003 PN was recognized as a sub-specialty of paediatrics and neurology by the Board of the European Union of Medical Specialties.

View Article and Find Full Text PDF

Laboratory investigations, whilst not essential to the diagnosis of seizures or of epilepsy, can be fundamental to determining the cause and guiding management. Over 50% of first seizures have an acute symptomatic cause, including a range of metabolic, toxic or infectious cause. The same triggers can precipitate status epilepticus, either de novo or as part of a deterioration in control in individuals with established epilepsy.

View Article and Find Full Text PDF

Background: Disordered thyroid hormone transport, due to mutations in the SLC16A2 gene encoding monocarboxylate transporter 8 (MCT8), is characterised by intellectual and motor disability resulting from cerebral hypothyroidism and chronic peripheral thyrotoxicosis. We sought to systematically assess the phenotypic characteristics and natural history of patients with MCT8 deficiency.

Methods: We did an international, multicentre, cohort study, analysing retrospective data from Jan 1, 2003, to Dec 31, 2019, from patients with MCT8 deficiency followed up in 47 hospitals in 22 countries globally.

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates the genetic variations in sodium channel genes (SCN1A, SCN2A, SCN3A, SCN8A) linked to epilepsy and neurodevelopmental disorders to enhance understanding of seizure susceptibility and develop better treatment approaches.* ! -
  • By analyzing data from 865 epilepsy patients and 114 functional studies, researchers identified common patterns in symptom presentation and discovered that SCN gene variations often lead to similar functional impacts but manifest differently in clinical settings based on neuron types.* ! -
  • Findings suggest that individuals with certain SCN mutations (especially gain-of-function) tend to experience early-onset epilepsy and are likely to respond well to sodium channel blockers, highlighting the potential for more tailored treatment strategies
View Article and Find Full Text PDF

The ketogenic diet (KD) is a high fat, low carbohydrate diet considered to be the treatment of choice for GLUT1deficiency syndrome, a metabolic disorder affecting the nervous system. To present our experience in four patients with GLUT1 deficiency syndrome who were treated with KD. Retrospective data from case series.

View Article and Find Full Text PDF

Infantile spasms (IS) is a developmental and epileptic encephalopathy with heterogeneous etiologies including many genetic causes. Genetic studies have identified pathogenic variants in over 30 genes as causes of IS. Many of these genetic causes are extremely rare, with only one reported incidence in an individual with IS.

View Article and Find Full Text PDF

Background: Deficiency of the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) causes severe intellectual and motor disability and high serum tri-iodothyronine (T) concentrations (Allan-Herndon-Dudley syndrome). This chronic thyrotoxicosis leads to progressive deterioration in bodyweight, tachycardia, and muscle wasting, predisposing affected individuals to substantial morbidity and mortality. Treatment that safely alleviates peripheral thyrotoxicosis and reverses cerebral hypothyroidism is not yet available.

View Article and Find Full Text PDF

Rett spectrum disorder is a progressive neurological disease and the most common genetic cause of intellectual disability in females. is the major causative gene. In addition, and mutations have been reported in Rett patients, especially with the atypical presentation.

View Article and Find Full Text PDF

Efficacy and safety of pregabalin as adjunctive treatment for children (aged 4-16 years) with partial-onset seizures, hereafter termed focal onset seizures for this study, was evaluated. This double-blind, randomized, placebo-controlled, international study had 3 phases: 8-week baseline, 12-week double-blind treatment (2-week dose escalation; 10-week fixed dose), and 1-week taper. Selection criteria included experiencing focal onset seizures and receiving a stable regimen of 1 to 3 antiepileptic drugs.

View Article and Find Full Text PDF

NBEA is a candidate gene for autism, and de novo variants have been reported in neurodevelopmental disease (NDD) cohorts. However, NBEA has not been rigorously evaluated as a disease gene, and associated phenotypes have not been delineated. We identified 24 de novo NBEA variants in patients with NDD, establishing NBEA as an NDD gene.

View Article and Find Full Text PDF

Epilepsy is a frequent feature of neurodevelopmental disorders (NDDs), but little is known about genetic differences between NDDs with and without epilepsy. We analyzed de novo variants (DNVs) in 6,753 parent-offspring trios ascertained to have different NDDs. In the subset of 1,942 individuals with NDDs with epilepsy, we identified 33 genes with a significant excess of DNVs, of which SNAP25 and GABRB2 had previously only limited evidence of disease association.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_sessionlgc0o895j0rnr3jnl848d3143kpk6jes): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once