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Neuro-Molecular Pathogenetic Mechanisms of Sudden Infant Death Syndrome (SIDS) and Other Infant Neurodevelopmental Disorders

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 20 May 2025 | Viewed by 2148

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Guest Editor
“Lino Rossi” Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS, Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy
Interests: neuropathology; autonomic nervous system; brain development; neurotransmitters; molecular neurology; SIDS
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Special Issue Information

Dear Colleagues,

Sudden Infant Death Syndrome (SIDS) is the leading cause of death among infants in the first year of age, with a frequency of 1 every 750–1000 live births. This syndrome refers to the sudden unexpected death of an infant under 1 year of age that remains unexplained after a thorough investigation, including a complete autopsy, detailed review of the circumstances of death and clinical history.

Even if the pathogenetic mechanism of SIDS has not yet been determined, neuropathology seems to be a consistent substrate. Subtle developmental abnormalities of brainstem nuclei checking the vital functions have been highlighted, frequently related to environmental risk factors (such as cigarette smoke, air pollution, pesticides, etc.). Exogenous toxic factors can in fact interact in complex ways with the genetic constitution of the infant, leading to polymorphisms and/or mutations of specific genes (such as polymorphisms of the serotonin transporter gene 5-HTT, the regulator of the synaptic serotonin concentration, frequently found in SIDS associated with hypoplasia of the raphe nuclei or mutations of genes required for cardiorespiratory activity that can predispose patients to SIDS).

Another aim of this proposal is to deepen the knowledge regarding developmental brain dysfunctions of the autonomic control that can be found in additional infant syndromes, such as Rett syndrome, cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder, Pitt–Hopkins syndrome, congenital central hypoventilation syndrome (CCHS), and GRIN1-related neurodevelopmental disorder, characterized by frequent association with insufficient expression or mutations of specific genes in the context of the interactions with environmental risk factors (e.g. early exposure to smoking, air and water pollution, pesticides, food contamination).

The aim of this Special Issue is to collect new contributions useful to explain the pathogenesis of SIDS and other childhood neurodevelopmental disorders and consequently provide useful data for planning effective prevention strategies.

Expert researchers in this field are encouraged to submit high-quality original research articles and reviews aimed to widen the current knowledge on the neuropathological and molecular mechanisms underlying these nervous developmental disorders, also considering the correlations with possible risk factors.

Prof. Dr. Anna Maria Lavezzi
Guest Editor

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Keywords

  • congenital central hypoventilation syndrome (CCHS)
  • cyclin-dependent kinase-like 5 (CDKL5)) deficiency disorder
  • GRIN1-related neurodevelopmental disorder 
  • SIDS
  • neuropathology
  • neurodevelopmental alterations
  • genetic polymorphisms
  • mutations
  • pollutants
  • Pitt-Hopkins syndrome
  • Rett syndrome
  • risk factors

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Published Papers (2 papers)

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Research

11 pages, 1237 KiB  
Article
New Step in Understanding the Pathogenetic Mechanism of Sudden Infant Death Syndrome: Involvement of the Pontine Reticular Gigantocellular Nucleus
by Anna Maria Lavezzi, Riffat Mehboob, Francesco Piscioli and Teresa Pusiol
Int. J. Mol. Sci. 2024, 25(13), 6920; https://doi.org/10.3390/ijms25136920 - 25 Jun 2024
Viewed by 783
Abstract
This study aimed to investigate, for the first time, the potential role of the gigantocellular nucleus, a component of the reticular formation, in the pathogenetic mechanism of Sudden Infant Death Syndrome (SIDS), an event frequently ascribed to failure to arouse from sleep. This [...] Read more.
This study aimed to investigate, for the first time, the potential role of the gigantocellular nucleus, a component of the reticular formation, in the pathogenetic mechanism of Sudden Infant Death Syndrome (SIDS), an event frequently ascribed to failure to arouse from sleep. This research was motivated by previous experimental studies demonstrating the gigantocellular nucleus involvement in regulating the sleep–wake cycle. We analyzed the brains of 48 infants who died suddenly within the first 7 months of life, including 28 SIDS cases and 20 controls. All brains underwent a thorough histological and immunohistochemical examination, focusing specifically on the gigantocellular nucleus. This examination aimed to characterize its developmental cytoarchitecture and tyrosine hydroxylase expression, with particular attention to potential associations with SIDS risk factors. In 68% of SIDS cases, but never in controls, we observed hypoplasia of the pontine portion of the gigantocellular nucleus. Alterations in the catecholaminergic system were present in 61% of SIDS cases but only in 10% of controls. A strong correlation was observed between these findings and maternal smoking in SIDS cases when compared with controls. In conclusion we believe that this study sheds new light on the pathogenetic processes underlying SIDS, particularly in cases associated with maternal smoking during pregnancy. Full article
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9 pages, 3321 KiB  
Article
Congenital LMNA-Related Muscular Dystrophy in Paediatrics: Cardiac Management in Monozygotic Twins
by Patricia Martínez Olorón, Iosune Alegría, Sergi Cesar, Bernat del Olmo, Estefanía Martínez-Barrios, Laura Carrera-García, Daniel Natera-de Benito, Andrés Nascimento, Oscar Campuzano and Georgia Sarquella-Brugada
Int. J. Mol. Sci. 2024, 25(11), 5836; https://doi.org/10.3390/ijms25115836 - 27 May 2024
Viewed by 848
Abstract
Pathogenic variants in LMNA have been associated with a wide spectrum of muscular conditions: the laminopathies. LMNA-related congenital muscular dystrophy is a laminopathy characterised by the early onset of symptoms and often leads to a fatal outcome at young ages. Children face [...] Read more.
Pathogenic variants in LMNA have been associated with a wide spectrum of muscular conditions: the laminopathies. LMNA-related congenital muscular dystrophy is a laminopathy characterised by the early onset of symptoms and often leads to a fatal outcome at young ages. Children face a heightened risk of malignant arrhythmias. No established paediatric protocols for managing this condition are available. We review published cases and provide insights into disease progression in two twin sisters with LMNA-related muscular dystrophy. Our objective is to propose a cardiac surveillance and management plan tailored specifically for paediatric patients. We present a family of five members, including two twin sisters with LMNA-related muscular dystrophy. A comprehensive neuromuscular and cardiac work-up was performed in all family members. Genetic analysis using massive sequencing technology was performed in both twins. Clinical assessment showed that only the twins showed diagnoses of LMNA-related muscular dystrophy. Follow-up showed an early onset of symptoms and life-threatening arrhythmias, with differing disease progressions despite both twins passing away. Genetic analysis identified a de novo rare missense deleterious variant in the LMNA gene. Other additional rare variants were identified in genes associated with myasthenic syndrome. Early-onset neuromuscular symptoms could be related to a prognosis of worse life-threatening arrhythmias in LMNA related muscular dystrophy. Being a carrier of other rare variants may be a modifying factor in the progression of the phenotype, although further studies are needed. There is a pressing need for specific cardiac recommendations tailored to the paediatric population to mitigate the risk of malignant arrhythmias. Full article
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