SNUPN deficiency causes a recessive muscular dystrophy due to RNA mis-splicing and ECM dysregulation.

SNURPORTIN-1, encoded by SNUPN, plays a central role in the nuclear import of spliceosomal small nuclear ribonucleoproteins. However, its physiological function remains unexplored. In this study, we investigate 18 children from 15 unrelated families who present with atypical muscular dystrophy and neurological defects. Nine hypomorphic SNUPN biallelic variants, predominantly clustered in the last coding exon, are ascertained to segregate with the disease. We demonstrate that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients' primary fibroblasts and CRISPR/Cas9-mediated mutant cell lines. Additionally, mutant nuclei exhibit defective spliceosomal maturation and breakdown of Cajal bodies. Transcriptome analyses reveal splicing and mRNA expression dysregulation, particularly in sarcolemmal components, causing disruption of cytoskeletal organization in mutant cells and patient muscle tissues. Our findings establish SNUPN deficiency as the genetic etiology of a previously unrecognized subtype of muscular dystrophy and provide robust evidence of the role of SPN1 for muscle homeostasis.

The Importance of Implementing a Transition Strategy for Patients with Muscular Dystrophy: From Child to Adult-Insights from a Tertiary Centre for Rare Neurological Diseases.

Progress in the field of muscular dystrophy (MD) using a multidisciplinary approach based on international standards of care has led to a significant increase in the life expectancy of patients. The challenge of transitioning from pediatric to adult healthcare has been acknowledged for over a decade, yet it continues to be a last-minute concern. Currently, there is no established consensus on how to evaluate the effectiveness of the transition process. Our study aimed to identify how well patients are prepared for the transition and to determine their needs. We conducted a descriptive, cross-sectional study on 15 patients aged 14 to 21 years. The patients completed a sociodemographic and a Transition Readiness Assessment Questionnaire (TRAQ). We also analyzed the comorbidities of these patients. Our study revealed that only 46.7% of the patients had engaged in a conversation with a medical professional, namely, a child neurologist, about transitioning. A total of 60% of the participants expressed having confidence in their self-care ability. However, the median TRAQ score of 3.6 shows that these patients overestimate themselves. We emphasize the necessity for a slow, personalized transition led by a multidisciplinary team to ensure the continuity of state-of-the-art care from pediatric to adult healthcare services and the achievement of the highest possible quality of life for these patients.

Autosomal Dominant Hypocalcemia Type 1 and Neonatal Focal Seizures.

Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism that is characterized by gain-of-function mutations in the CASR gene, which provides instructions for producing the protein called calcium-sensing receptor (CaSR). Hypocalcemia in the neonatal period has a wide differential diagnosis. We present the case of a female newborn with genetic hypoparathyroidism (L125P mutation of CASR gene), hypocalcemia, and neonatal seizures due to the potential correlation between refractory neonatal seizures and ADH1. Neonatal seizures were previously described in patients with ADH1 but not in association with the L125P mutation of the CASR gene. Prompt diagnosis and management by a multidisciplinary and an appropriate therapeutic approach can prevent neurological and renal complications.

Pediatric Autoimmune Encephalitis: Practical Aspects.

Autoimmune encephalitis is an inflammatory condition of the central nervous system that may involve a widely variable spectrum of clinical features. It can be divided into two main groups: with antibodies against intracellular antigens and with antibodies against surface antigens. The main clinical presentation is characterized by psychiatric symptoms, movement disorders and seizures. The differential diagnosis process should mainly consist of excluding infectious or other causes of encephalitis. Brain imagining, cerebrospinal fluid analysis and serology for a wide range of antibodies should lead to the diagnosis of a specific type of autoimmune encephalitis. Considering the fact that the disease may be paraneoplastic, appropriate tumor screening should be performed. Once the autoimmune etiology is established, treatment consists mainly of escalating immune therapies.

Treatment of Pediatric Migraine: a Review.

Migraine is a common, but often underdiagnosed complaint in children and the lack of studies regarding its treatment in this particularly population makes it harder to enlarge the choices of treatment. However, recent trials made it easier to utilize newer compounds that improve the outcome of the disease. We reviewed the treatment of pediatric migraine and divided therapeutic methods into two broad areas: treatment of the acute attack - used both in the emergency room and as home options and prophylactic agents. Not to be forgotten when talking about treating migraine in children and adolescents is the support therapies offered alongside the classical approach by teams formed by the pediatric neurologist, pediatrician, psychologist, support groups and the families of the patients.