Cristina Pereira

A PRRT2 é uma proteína membranar plasmática pré-sináptica envolvida na libertação de neurotransmissores. As doenças associadas às variantes patogénicas do PRRT2 incluem um espectro de condições de hereditariedade autossómica dominante e apresentação paroxística. As três principais são a epilepsia autolimitada do lactente, a discinésia paroxística cinesigénica e a enxaqueca hemiplégica, mas outras apresentações têm sido reportadas. Os indivíduos com variantes patogénicas do PRRT2 podem apresentar-se com um ou mais fenótipos em simultâneo ou de forma subsequente. Relatamos 5 casos de epilepsia autolimitada do lactente com início entre os 4 e 10 meses e 1 caso de discinésia paroxística cinesigénica aos 8 anos, todos associados à variante patogénica c.649dup p.(Arg217Profs*8) em heterozigotia do PRRT2. Esta série de casos ilustra o espetro clínico inter e intra-individual, a variabilidade fenotípica inter e intra-familiar, a boa resposta à terapêutica com bloqueadores dos canais de sódio e o carácter autolimitado desta doença.

Rett syndrome (RTT) is a neurological disorder caused by mutations in the MECP2 gene. It is characterized by apparently normal early neurodevelopment followed by psychomotor regression between 6 and 18 months. There is no cure, and treatment is multidisciplinary, focusing on improving quality of life and functionality. This study aims to characterize RTT patients and evaluate clinical patterns, interventions, and outcomes. A retrospective cohort study was conducted of children diagnosed with RTT and a pathogenic MECP2 variant, followed at a Portuguese tertiary pediatric hospital from 2010 to 2024. Electronic medical records were reviewed, and epidemiological and clinical data were collected. Twelve RTT patients were followed (91.7% female). The median age at symptom onset was 15 months, and at diagnosis, 35 months. Seven patients (58.3%) had classic RTT. Molecular analysis identified 10 different MECP2 variants, all de novo mutations. Epilepsy and constipation were the most common comorbidities. Five patients (41.7%) were wheelchair-dependent, and two required non-invasive respiratory support. Almost all patients received physical, occupational, and speech therapies. The median number of chronic medications per patient was two, primarily anticonvulsants. The median number of medical specialties per patient was two, with neuropediatrics and neurodevelopmental pediatrics being the most frequent. Conclusions: RTT prevalence remained stable over 20 years, with a decreased median age at diagnosis, likely due to increased awareness and genetic testing. No clear genotype–phenotype correlation was found. RTT diagnosis remains based on clinical features, particularly neurodevelopmental regression. A multidisciplinary approach was critical, with patients receiving various therapies and support. This study provides valuable insights into RTT in Portugal, contributing to global knowledge. What is known:• Rett syndrome is a rare neurodevelopmental disorder primarily affecting females, characterized by regression of motor and communication skills.• Limited long-term data exist on clinical progression and functional outcomes in pediatric Rett syndrome. What is new:• A decreasing age at diagnosis was observed, likely reflecting increased awareness and access to genetic testing.• In an era of promising clinical trials for potential curative treatments, an individualized, multidisciplinary approach remains the standard of care in most countries, including Portugal.

Acute cerebellitis is a rare disease resulting from dysfunction of the cerebellum or its connections, with infectious or inflammatory causes, varied clinical manifestations, and evidence of predominantly cerebellar inflammation on magnetic resonance imaging (MRI). It belongs to the spectrum of acute post-infectious cerebellar ataxia, a self-limited disease whose therapeutic approach is individualized. Three clinical cases of cerebellar ataxia in pediatric age are described. In case 1, there is a post-infectious context associated with Epstein-Barr virus. In case 2, there is a possible Mycoplasma pneumoniae post-infectious context, with MRI revealing cerebellar inflammation. Steroids were used in both cases. Case 3 presents severe cerebellar post-infection symptoms associated with varicella zoster virus, and human immunoglobulin was given. Evolution was favorable in all. These cases demonstrate the variable spectrum of post-infectious cerebellar ataxia and the different therapeutic options used, depending on the clinical presentation and individual characteristics of affected children.

A palette of copy number changes in long-term epilepsy-associated tumors (LEATs) have been reported, but the data are heterogeneous. To better understand the molecular basis underlying the development of LEATs, we performed array-comparative genomic hybridization analysis to investigate chromosomal imbalances across the entire genome in 8 cases of LEATs. A high number of aberrations were found in 4 patients, among which deletions predominated. Both whole-chromosome and regional abnormalities were observed, including monosomy 19, deletion of 1p, deletions of 4p, 12p, and 22q, and gain of 20p. The common altered regions are located mainly on chromosomes 19 and 4p, identifying genes potentially involved in biological processes and cellular mechanisms related to tumorigenesis. Our study highlights new genomic alterations and reinforces others previously reported, offering new molecular insights that may help in diagnosis and therapeutic decision-making.

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