Lissencephaly, Pachygyrias, Band Heterotopias, RELN Pathway, and ARX Mutations (Incomplete Neuron Migration)

Laura Sciuto; Valeria Fichera; Antonio Zanghì; Michele Vecchio; Raffaele Falsaperla; Sebastiano Galioto; Stefano Palmucci; Giuseppe Belfiore; Claudia Di Napoli; Agata Polizzi; Andrea D. Praticò

doi:10.1055/s-0044-1786790

Journal of Pediatric Neurology, Table of Contents

Journal of Pediatric Neurology 2024; 22(05): 332-340
DOI: 10.1055/s-0044-1786790

Review Article

Lissencephaly, Pachygyrias, Band Heterotopias, RELN Pathway, and ARX Mutations (Incomplete Neuron Migration)

Laura Sciuto‡^*

¹Pediatrics Postgraduate Residency Program, University of Catania, Catania, Italy

,

Valeria Fichera‡^*

¹Pediatrics Postgraduate Residency Program, University of Catania, Catania, Italy

,

Antonio Zanghì‡^*

²Department of Medical and Surgical Sciences and Advanced Technologies, Research Center for Surgery of Complex Malformation Syndromes of Transition and Adulthood, University of Catania, Catania, Italy

,

Michele Vecchio

³Rehabilitation Unit, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy

,

Raffaele Falsaperla

⁴Neonatal Intensive Care unit and Neonatology, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy

,

Sebastiano Galioto

⁵Department of Medical Surgical Sciences and Advanced Technologies, University Hospital Policlinico “G. Rodolico-San Marco,” Catania, Italy

,

Stefano Palmucci

⁶Department of Medical Surgical Sciences and Advanced Technologies, IPTRA Unit, University Hospital Policlinico “G. Rodolico-San Marco,” Catania, Italy

,

Giuseppe Belfiore

⁷Department of Medical Surgical Sciences and Advanced Technologies, Unit of Radiology 1, University Hospital Policlinico “G. Rodolico-San Marco,” Catania, Italy

,

Claudia Di Napoli

⁸Chair of Genetics, Department of Medicine and Surgery, Kore University, Enna, Italy

,

Agata Polizzi

⁹Chair of Pediatrics, Department of Educational Sciences, University of Catania, Catania, Italy

,

Andrea D. Praticò

¹⁰Chair of Pediatrics, Department of Medicine and Surgery, Kore University, Enna, Italy

› Author Affiliations

Abstract

Lissencephaly (LIS) is a group of malformations of cortical development consisting of a defective neuronal migration that results in lack of formation of the normal cerebral convolutions. It includes a spectrum of defect with varying degrees of severity, from agyria and pachygyria to subcortical band heterotopia. The etiopathogenesis of LIS includes both genetic and environmental factors. Although nongenetic forms of LIS have been reported, genetic causes are certainly more frequent and to date 19 LIS-SBH-associated genes have been identified. Most common mutations involve LIS1, DCX, ARX, and RELN genes. Clinically affected individuals present with early hypotonia, which can progress to limb spasticity, seizures, and psychomotor retardation. Convulsive episodes usually appear early (first months of life) and include infantile spasms, akinetic or myoclonic seizures, up to the development of complex epileptic syndromes, including atypical absences, myoclonia, and partial or tonic–clonic seizures. Several clinical entities are associated with classical LIS, including the following: isolated lissencephaly sequence (ILS); Miller–Dieker syndrome (MDS; OMIM 247200); subcortical band heterotopia (OMIM 300067); X-linked LIS with abnormal genitalia; and LIS with cerebellar hypoplasia. Diagnosis primarily depends on genetic and neuroimaging. Magnetic resonance imaging (MRI) is the gold standard, and it detects the presence of thick cortical cortex, its location, and the layers' architecture. Based on neuroimaging, it is possible to distinguish six subtypes of gyral malformations. Clinical and therapeutic management of these patients is challenging, considering the necessity to face drug-resistant epilepsy, intellectual disability, spasticity, and dysphagia and feeding problems. At the present moment, no gene-specific treatment for LIS is available.

Keywords

lissencephaly - pachygyria - brain malformation - genetics - syndromes

Full Text

References

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