Methylation assay in KMT2B-related dystonia: a novel diagnostic validation tool.

Background/objectives: KMT2B-related dystonia (DYT28, OMIM #617284) is a progressive neurological condition characterized by early onset movement disorders with autosomal dominant inheritance. In this study, we describe the use of a genome methylation episignature methodology to functionally validate two variants of uncertain significance (VUS) in the KMT2B gene.

Methods: Genome-wide methylation status was assessed using the EPIC methylation assay in peripheral blood samples from two subjects with early onset movement disorder and missense variants of uncertain significance in the KMT2B gene (p.

Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders.

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.

Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analysed detailed clinical and genetic data for all individuals.

Young-Onset Alzheimer Dementia Due to a Novel Pathogenic Variant Initially Misdiagnosed as Autoimmune Encephalitis.

Objectives: Pathogenic variants in presenilin 1 are related to early-onset Alzheimer disease (AD) and may occur as de novo variants. In comparison with sporadic forms, it can present with psychiatric manifestations, seizures, myoclonus, and focal presentation. Because PSEN1 can occur in young patients who lack a family history of neurologic disorders and because these symptoms are also frequent in autoimmune encephalitis (AE), diagnosis may be overlooked.

Expanding the spectrum of phenotypes for MPDZ: Report of four unrelated families and review of the literature.

MPDZ, a gene with diverse functions mediating cell-cell junction interactions, receptor signaling, and binding multivalent scaffold proteins, is associated with a spectrum of clinically heterogeneous phenotypes with biallelic perturbation. Despite its clinical relevance, the mechanistic underpinnings of these variants remain elusive, underscoring the need for extensive case series and functional investigations. In this study, we conducted a systematic review of cases in the literature through two electronic databases following the PRISMA guidelines.

Myoclonus improvement after seizures in progressive myoclonic epilepsy type 7: a case report.

Background: Progressive Myoclonic Epilepsy (PME) is a group of rare diseases that are difficult to differentiate from one another based on phenotypical characteristics.

Case Report: We report a case of PME type 7 due to a pathogenic variant in KCNC1 with myoclonus improvement after epileptic seizures.

Discussion: Myoclonus improvement after seizures may be a clue to the diagnosis of Progressive Myoclonic Epilepsy type 7.

A needle in a haystack? The impact of a targeted epilepsy gene panel in the identification of a treatable but rapidly progressive metabolic epilepsy: CLN2 disease.

Background:  Neuronal ceroid lipofuscinoses (NCL) are a group of autosomal recessive, inherited, lysosomal, and neurodegenerative diseases that causes progressive dementia, seizures, movement disorders, language delay/regression, progressive visual failure, and early death. Neuronal ceroid lipofuscinosis type 2 (CLN2), caused by biallelic pathogenic variants of the gene, is the only NCL with an approved targeted therapy. The laboratory diagnosis of CLN2 is established through highly specific tests, leading to diagnostic delays and eventually hampering the provision of specific treatment for patients with CLN2.

Pediatric palliative care for metabolic diseases: 20-year epidemiological survey of outpatients at a Brazilian quaternary hospital.

The interface between pediatric palliative care (PPC) and inborn metabolic diseases (IMD) remains incipient, though these conditions fill the state of art of complex chronic diseases, eligible to this health approach. We analyzed the medical records of PPC clinic during the years 2001 to 2021 and the IMD outpatients. We established a parallel with the world scientific literature concerning the epidemiology of PPC and IMD.

Identifying high-risk neurological phenotypes in adult-onset classic monogenic autoinflammatory diseases: when should neurologists consider testing?

Background: Monogenic autoinflammatory disorders result in a diverse range of neurological symptoms in adults, often leading to diagnostic delays. Despite the significance of early detection for effective treatment, the neurological manifestations of these disorders remain inadequately recognized.

Methods: We conducted a systematic review searching Pubmed, Embase and Scopus for case reports and case series related to neurological manifestations in adult-onset monogenic autoinflammatory diseases.

X-Linked Levodopa-Responsive Parkinsonism-Epilepsy Syndrome: A Novel PGK1 Mutation and Literature Review.

Background: Genetic underpinnings in Parkinson's disease (PD) and parkinsonian syndromes are challenging, and recent discoveries regarding their genetic pathways have led to potential gene-specific treatment trials.

Cases: We report 3 X-linked levodopa (l-dopa)-responsive parkinsonism-epilepsy syndrome cases due to a hemizygous variant in the phosphoglycerate kinase 1 (PGK1) gene. The likely pathogenic variant NM_000291.

Gerstmann-Sträussler-Scheinker Disease Presenting as Late-Onset Slowly Progressive Spinocerebellar Ataxia, and Comparative Case Series with Neuropathology.

Background: Genetic prion diseases, including Gerstmann-Sträussler-Scheinker disease (GSS), are extremely rare, fatal neurodegenerative disorders, often associated with progressive ataxia and cognitive/neuropsychiatric symptoms. GSS typically presents as a rapidly progressive cerebellar ataxia, associated with cognitive decline. Late-onset cases are rare.

Expanding the phenotypic spectrum of -related leucoencephalopathy and ataxia.

Mutations in are a rare cause of autosomal recessive leucoencephalopathy with ataxia and specific imaging abnormalities. Very few cases have been reported to date. Here, we describe the clinical and imaging phenotype of 12 additional patients and expand the known phenotypic spectrum of this disorder.

Novel ERLIN2 variant expands the phenotype of Spastic Paraplegia 18.

Background: The Brazilian Northeast region is notable for its high prevalence of consanguineous marriages and isolated populations, which has led to a significant prevalence of rare genetic disorders. This study describes the clinical presentation of four affected individuals from the same family, comprising two siblings and their cousins, with ages ranging from 11 to 20 years.

Methods: In a small and isolated community in Northeastern Brazil, affected individuals initially underwent a clinical assessment.

Subacute Partially Reversible Leukoencephalopathy Expands the Aicardi-Goutières Syndrome Phenotype.

Objective: To report a series of atypical presentations of Aicardi-Goutières syndrome.

Methods: Clinical, neuroimaging, and genetic data.

Results: We report a series of six unrelated patients (five males) with a subacute loss of developmental milestones, pyramidal signs, and regression of communication abilities, with onset at ages ranging from 7 to 20 months, reaching a nadir after 4 to 24 weeks.

Neuropsychological Characterization of Autosomal Recessive Intellectual Developmental Disorder 59 Associated with IMPA1 (MRT59).

Biallelic loss of function of causes autosomal recessive intellectual developmental disorder 59 (MRT59, OMIM #617323). MRT59 has been reported to present with significant intellectual disability and disruptive behavior, but little is known about the neurocognitive pattern of those patients. Thus, the aims of this study were: (1) to assess the cognitive profile of these patients, and (2) to evaluate their functional dependence levels.

A case of mitochondrial DNA depletion syndrome type 11 - expanding the genotype and phenotype.

Mitochondrial DNA depletion syndrome type 11 (MTDPS11) is caused by pathogenic variants in MGME1 gene. We report a woman, 40-year-old, who presented slow progressive drop eyelid at 11-year-old with, learning difficulty and frequent falls. Phisical examination revealed: mild scoliosis, elbow hyperextensibility, flat feet, chronic progressive external ophthalmoplegia with upper eyelid ptosis, diffuse hypotonia, and weakness of arm abduction and neck flexion.

Toward healthy and sustainable diets for the 21st century: Importance of sociocultural and economic considerations.

Four years after the EAT-Lancet landmark report, worldwide movements call for action to reorient food systems to healthy diets that respect planetary boundaries. Since dietary habits are inherently local and personal, any shift toward healthy and sustainable diets going against this identity will have an uphill road. Therefore, research should address the tension between the local and global nature of the biophysical (health, environment) and social dimensions (culture, economy).

Monitoring Cell Adhesion on Polycaprolactone-Chitosan Films with Varying Blend Ratios by Quartz Crystal Microbalance with Dissipation.

A detailed understanding of the cell adhesion on polymeric surfaces is required to improve the performance of biomaterials. Quartz crystal microbalance with dissipation (QCM-D) as a surface-sensitive technique has the advantage of label-free and real-time monitoring of the cell-polymer interface, providing distinct signal patterns for cell-polymer interactions. In this study, QCM-D was used to monitor human fetal osteoblastic (hFOB) cell adhesion onto polycaprolactone (PCL) and chitosan (CH) homopolymer films as well as their blend films (75:25 and 25:75).

New observations on minifascicular neuropathy with sex-dependent gonadal dysgenesis: a case series with nerve ultrasound assessment.

Background: Gonadal dysgenesis with minifascicular neuropathy (GDMN) is a rare autosomal recessive condition associated with biallelic DHH pathogenic variants. In 46, XY individuals, this disorder is characterized by an association of minifascicular neuropathy (MFN) and gonadal dysgenesis, while in 46, XX subjects only the neuropathic phenotype is present. Very few patients with GDMN have been reported so far.