A Case of Paroxysmal Exercise-Induced Dyskinesia Expands the Phenotypic spectrum of NAXE-Related Encephalopathy.

Non-convulsive status epilepticus revealing acute deterioration in AARS2 mutation–associated progressive leukoencephalopathy

Unprecedented overlap of Tourette syndrome and drug-resistant epilepsy in a young patient with Bardet–Biedl syndrome: A case report

Introduction: Drug-resistant epilepsy affects approximately 25% of patients with epilepsy and requires complex, multidisciplinary therapeutic approaches. When associated with neuropsychiatric comorbidities and rare genetic syndromes, such as Bardet–Biedl syndrome (BBS), a primary ciliopathy, diagnostic and therapeutic challenges are further intensified. Case presentation: A Brazilian male patient with neuropsychomotor developmental delay, hereditary retinopathy, and motor and vocal tics since childhood was evaluated at 10 years of age due to involuntary movements, vocalizations, and behavioral disturbances. He was diagnosed with autism spectrum disorder (ASD), mild intellectual disability, and Tourette syndrome (TS), accompanied by intermittent psychotic symptoms. At 16 years of age, he developed a complex epilepsy phenotype characterized by focal seizures associated with visual hallucinations, progressing to bilateral tonic– clonic seizures. Recurrent episodes of functional/dissociative seizures were also observed. The patient subsequently underwent whole-exome sequencing, which led to the diagnosis of BBS type 1, accounting for the multisystem involvement and the clinical complexity of the case. Discussion: This case expands the clinical spectrum of BBS by documenting the coexistence of its classical manifestations with TS, ASD, refractory epilepsy, and functional dissociative seizures. Although ASD is increasingly recognized as a neurodevelopmental comorbidity in ciliopathies, persistent tic disorders remain rarely reported, suggesting that ciliary dysfunction may contribute to susceptibility to complex neurodevelopmental phenotypes. Conclusion: This case illustrates a rare and previously undescribed overlap between clinical findings consistent with TS and a complex epileptic phenotype. Furthermore, in the context of initial diagnostic uncertainty, genetic sequencing was essential to confirm the diagnosis of BBS.

RFX3 Pathogenic Variants as a Rare Cause of Infantile Epileptic Spasms Syndrome

This case expands the clinical spectrum associated with RFX3 variants, supporting a potential role in IESS and early neurodevelopmental disruption, and highlights the relevance of including RFX3 in the genetic evaluation of patients with IESS and co-occurring neurodevelopmental disorders.

Kufor-Rakeb Syndrome: Recognising a Rare Genetic Cause of Early-Onset Parkinsonism

Background: Kufor–Rakeb syndrome (KRS) is a rare inherited neurodegenerative disorder caused by pathogenic variants in the ATP13A2 gene. It is characterised by juvenile-onset parkinsonism with progressive cognitive, neuropsychiatric, pyramidal, and bulbar manifestations. Case Presentation: A 22-year-old boy presented with approximately 2.5 years of progressive cognitive and behavioural decline, followed by bulbar dysfunction and motor impairment. Symptoms began at 19.5 years of age with cognitive and behavioural changes; speech impairment and dysphagia developed during the subsequent months, and motor difficulties became prominent approximately one year after symptom onset. Neurological examination demonstrated cognitive impairment, hypomimia, generalised rigidity, dysarthria, brisk lower-limb deep tendon reflexes, and bilateral extensor plantar responses. Routine laboratory investigations and targeted metabolic and disease-specific evaluations were unrevealing. Clinical exome sequencing identified a homozygous pathogenic variant in the ATP13A2 gene, c.2629G>A (p.Gly877Arg), confirming KRS. Conclusion: KRS should be considered in adolescents with progressive cognitive decline and juvenile-onset parkinsonism, particularly when routine investigations are non-diagnostic. Genetic testing is central to diagnosis and enables genetic counselling and multidisciplinary supportive care.

Rasmussen syndrome in a pediatric patient: case report

Introduction: Rasmussen’s Syndrome (RS) is a rare, chronic, and progressive encephalitis, presumably of autoimmune origin, that predominantly affects children. It is characterized by drug-resistant focal seizures, progressive neurological deterioration, and cerebral hemispheric atrophy. Objective: To describe the clinical course, therapeutic challenges, and outcome of a pediatric patient with Rasmussen’s syndrome. Case Report: This case describes an 8-year-old female patient with a history of delayed neuropsychomotor development who developed drugresistant focal epilepsy. The diagnosis of RS was confirmed following clinical and imaging investigations. Functional hemispherectomy was indicated due to refractoriness to medical treatment. The procedure was temporarily postponed due to SARS-CoV-2 infection and was later performed successfully. The patient developed complications postoperatively, including hemodynamic instability, electrolyte disturbances, diabetes insipidus, respiratory infections, and acute kidney injury. Complete seizure control was achieved after approximately 65 days of hospitalization. Results: This case highlights the complexity of managing RS in pediatric patients and emphasizes the importance of an individualized approach. Conclusion: Hemispherectomy proved effective in controlling seizures and stabilizing neurological progression.

Developmental encephalopathy concomitant with aphasia associated with a pathogenic variant in the GRIN2A gene

Mutations in the GRIN gene family, which encode subunits of the NMDA (N-methyl-D-aspartate) receptor, have been increasingly associated with a spectrum of neurodevelopmental disorders. Among them, GRIN2A mutations play a crucial regulatory role in the receptor's function, affecting synaptic transmission and brain plasticity. This case study presents the clinical and genetic profile of a pediatric patient with a pathogenic GRIN2A mutation, highlighting the associated neurological phenotype, diagnostic process, and treatment approach. Clinical data were collected through neurological assessments, EEG, MRI, and comprehensive genetic testing, including next-generation sequencing (NGS), with confirmation by Sanger sequencing. The patient's symptoms, including developmental delay, epileptic episodes, and behavioral abnormalities, were analyzed in the context of current literature on GRIN-related disorders The identified pathogenic GRIN2A mutation correlated with a neurodevelopmental phenotype characterized by early-onset epilepsy, hypotonia, and intellectual disability. The above case highlights the importance of early genetic testing in children with neurodevelopmental disorders and aphasia, as well as co-occurring epilepsy. Understanding the functional impact of specific GRIN2A mutations can guide personalized treatment strategies and contribute to a better characterization of the GRINopathy spectrum.