Publications by authors named "Diane Doummar"

Article Synopsis
  • Dyskinetic disorders (-RD) are a set of neurodevelopmental and movement issues caused by gene variants, with dyskinetic crises characterized by sudden, intense abnormal movements that pose treatment challenges.
  • The study utilized a Delphi consensus method with international experts to create a framework on dyskinetic crises, covering definitions, triggers, diagnostic criteria, complications, and management strategies.
  • The consensus defined dyskinetic crises, noted potential triggers like stress and infections, suggested acute management options such as benzodiazepines, and stressed the need for better education for parents and caregivers to facilitate early recognition and intervention.
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  • Biallelic variants in the ZBTB11 gene are linked to a rare intellectual developmental disorder known as MRT69, which shows a variety of clinical symptoms.
  • The study focused on analyzing clinical and genetic traits of 29 individuals (ages 2-50) with these variants, finding diverse neurodevelopmental issues and complex movement disorders among the patients.
  • Results revealed that many patients had abnormal movements (like ataxia and dystonia) and cataracts, with one patient showing improvement from deep brain stimulation, contributing 13 new genetic variants to the understanding of ZBTB11-related disorders.
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Background: Heterozygous loss-of-function variants in CHD8 have been associated with a syndromic neurodevelopmental-disease spectrum, collectively referred to as CHD8-related neurodevelopmental disorders. Several different clinical manifestations, affecting neurodevelopmental and systemic domains, have been described, presenting with highly variable expressivity. Some expressions are well established and comprise autism spectrum disorders, psychomotor delay with cognitive impairment, postnatal overgrowth with macrocephaly, structural brain abnormalities, gastrointestinal disturbances, and behavioral and sleep-pattern problems.

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Central nervous system (CNS) dural arteriovenous fistulas (DAVF) have been reported in PTEN-related hamartoma tumor syndrome (PHTS). However, PHTS-associated DAVF remain an underexplored field of the PHTS clinical landscape. Here, we studied cases with a PTEN pathogenic variant identified between 2007 and 2020 in our laboratory (n = 58), and for whom brain imaging was available.

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Background: Essential tremor (ET) is considered the most frequent abnormal movement in the general population, with childhood onset in 5 to 30% of the patients.

Methods: A multicenter, descriptive cross-sectional study enrolled patients ⩽18 years with a definite diagnosis of ET according to the International Parkinson and Movement Disorders Society criteria. Demographic data, clinical and electrophysiological characteristics of the tremor, neurological examination and impact on quality of life were collected.

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Background And Objective: GLUT1 deficiency syndrome (Glut1DS) is a treatable neurometabolic disease that causes a wide range of neurologic symptoms in children and adults. However, its diagnosis relies on an invasive test, that is, a lumbar puncture (LP) to measure glycorrhachia, and sometimes complex molecular analyses of the gene. This procedure limits the number of patients able to receive the standard of care.

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Article Synopsis
  • Pathogenic variants in KMT5B, a lysine methyltransferase, are linked to global developmental issues, macrocephaly, autism, and other congenital anomalies, but the disorder is still not fully understood.
  • A study examining 43 patients revealed new significant features like hypotonia and congenital heart defects not previously associated with this condition.
  • Research using patient cell lines and KMT5B knockout mice showed that these variants lead to slow growth and highlighted alterations in pathways related to nervous system development, enhancing our understanding of the disorder's molecular mechanisms.
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Background And Purpose: HIBCH and ECHS1 genes encode two enzymes implicated in the critical steps of valine catabolism, 3-hydroxyisobutyryl-coenzyme A (CoA) hydrolase (HIBCH) and short-chainenoyl-CoA hydratase (ECHS1), respectively. HIBCH deficiency (HIBCHD) and ECHS1 deficiency (ECHS1D) generate rare metabolic dysfunctions, often revealed by neurological symptoms. The aim of this study was to describe movement disorders spectrum in patients with pathogenic variants in ECHS1 and HIBC.

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Background: Most reported patients carrying GNAO1 mutations showed a severe phenotype characterized by early-onset epileptic encephalopathy and/or chorea.

Objective: The aim was to characterize the clinical and genetic features of patients with mild GNAO1-related phenotype with prominent movement disorders.

Methods: We included patients diagnosed with GNAO1-related movement disorders of delayed onset (>2 years).

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Article Synopsis
  • The study identifies 15 new genetic alterations linked to KCNK9 imprinting syndrome (KIS) by analyzing 47 affected individuals, revealing a diverse genetic and phenotypic spectrum.
  • It highlights common symptoms of KIS, such as motor and speech delays, intellectual disabilities, and behavioral issues, while also discovering an additional mutational hotspot in the gene involved.
  • The research emphasizes that KIS is characterized by complex channel function alterations, which can aid in molecular diagnosis since clinical features alone are insufficient for identification.
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Purpose: CTR9 is a subunit of the PAF1 complex (PAF1C) that plays a crucial role in transcription regulation by binding CTR9 to RNA polymerase II. It is involved in transcription-coupled histone modification through promoting H3K4 and H3K36 methylation. We describe the clinical and molecular studies in 13 probands, harboring likely pathogenic CTR9 missense variants, collected through GeneMatcher.

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  • ADCY5-related dyskinesia is an early-onset movement disorder without an established treatment, but there's anecdotal evidence suggesting caffeine may help improve symptoms.
  • A worldwide study involving 30 patients indicated that caffeine was well tolerated, with 87% reporting symptom improvement, including reduced movement disorder frequency and enhanced quality of life.
  • The study concludes that caffeine could be a viable first-line treatment option for patients with ADCY5-related dyskinesia.
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Aim: KCNB1 encephalopathy encompasses a broad phenotypic spectrum associating intellectual disability, behavioral disturbances, and epilepsies of various severity. Using standardized parental questionnaires, we aimed to capture the heterogeneity of the adaptive and behavioral features in a series of patients with KCNB1 pathogenic variants.

Methods: We included 25 patients with a KCNB1 encephalopathy, aged from 3.

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  • Pathogenic variants in the MYT1L gene lead to a neurodevelopmental disorder characterized by features like developmental delays, intellectual disabilities, and behavioral disorders.
  • A study analyzed genetic data from 40 previously unreported patients, adding to a total of 62 patients to better understand the clinical characteristics and genotype-phenotype correlations.
  • The research confirmed key phenotypic traits, introduced new clinical features, and emphasized that patients with certain genetic variants do not show distinct clinical differences, aiding in improved diagnosis and management of the disorder.
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Article Synopsis
  • - CHD8 loss-of-function variants, initially linked to autism, are now linked to a broader range of neurodevelopmental disorders, including dystonia.
  • - Two unrelated patients with childhood-onset progressive dystonia were found to have different CHD8 variants through whole-exome sequencing.
  • - Both patients exhibited similar symptoms and showed clinical improvement after deep brain stimulation, suggesting that CHD8 mutations can lead to dystonia as a primary feature.
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Biallelic variants in PUS3 have recently been recognized as a rare cause of neurodevelopmental disorders. Pseudouridine synthase-3 encoded by PUS3 is an enzyme important for modification of various RNAs, including transfer RNA (tRNA). Here we present the clinical and genetic features of 21 individuals with biallelic PUS3 variants: seven new and 14 previously reported individuals, where clinical features of two were updated.

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The phenotypic spectrum of STXBP1-related encephalopathy ranges from infantile epileptic encephalopathy to intellectual disability with nonsyndromic or absent epilepsy. Although being frequently reported, the tremor associated with STXBP1 has not been fully characterized to date. The aim of our study was to describe it.

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De novo missense variants in encoding Kv10.1 are responsible for two clinically recognisable phenotypes: Temple-Baraitser syndrome (TBS) and Zimmermann-Laband syndrome (ZLS). The clinical overlap between these two syndromes suggests that they belong to a spectrum of -related encephalopathies.

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To characterize the electro-clinical presentation of patients with pyridoxine-dependent epilepsy (PDE) and pyridoxal phosphate (PLP)-dependent epilepsy in order to determine whether some of them could be diagnosed as West syndrome, i. e., West syndrome that starts after the age of 2 months without other types of seizures (focal seizures for instance) before the onset of epileptic spasms.

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Objective: To explore the phenotypic spectrum of -related disorders and specifically to determine whether patients fulfill criteria for alternating hemiplegia of childhood (AHC), we report the clinical features of 11 affected individuals.

Methods: Individuals with -related disorders were identified through a movement disorder clinic at a specialist pediatric center, with additional cases identified through collaboration with other centers internationally. Clinical data were acquired through retrospective case-note review.

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Megalencephaly-CApillary malformation-Polymicrogyria (MCAP) syndrome results from somatic mosaic gain-of-function variants in PIK3CA. Main features are macrocephaly, somatic overgrowth, cutaneous vascular malformations, connective tissue dysplasia, neurodevelopmental delay, and brain anomalies. The objectives of this study were to describe the clinical and radiological features of MCAP, to suggest relevant clinical endpoints applicable in future trials of targeted drug therapy.

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