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Journal of Pediatric Neurology
DOI: 10.1055/s-0044-1786787
Special Issue Article

Megalencephaly: Classification, Genetic Causes, and Related Syndromes

Roberta Leonardi‡   *
1   Pediatrics Postgraduate Residency Program, University of Catania, Catania, Italy
,
Laura Licciardello‡   *
1   Pediatrics Postgraduate Residency Program, University of Catania, Catania, Italy
,
Antonio Zanghì‡   *
2   Research Center for Surgery of Complex Malformation Syndromes of Transition and Adulthood, Department of Medical and Surgical Sciences and Advanced Technologies, University of Catania, Catania, Italy
,
Daria La Cognata
1   Pediatrics Postgraduate Residency Program, University of Catania, Catania, Italy
,
Antonino Maniaci
3   Chair of Otorhinolaryngology, Department of Medicine and Surgery, Kore University, Enna, Italy
,
Michele Vecchio
4   Rehabilitation Unit, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
,
Agata Polizzi
5   Chair of Pediatrics, Department of Educational Sciences, University of Catania, Catania, Italy
,
Raffaele Falsaperla
6   Neonatal Intensive Care Unit and Neonatology, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
,
Andrea D. Praticò
7   Chair of Pediatrics, Department of Medicine and Surgery, Kore University 94100, Enna, Italy
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Abstract

Megalencephaly is a developmental disorder due to an abnormal neuronal proliferation and migration during intrauterine or postnatal brain development that leads to cerebral overgrowth and neurological dysfunction. This cerebral overgrowth may affect the whole encephalon or only a region; when it involves one hemisphere it is referred to as hemimegalencephaly. Megalencephaly presents with a head circumference measurement of 2 standard deviations above the average measure for age. This group of disorders is clinically characterized by early onset and refractory to therapy epilepsy, neurodevelopmental disorders, behavioral problems, and autism spectrum disorder. Syndromic forms of megalencephaly should be considered when associated with other congenital abnormalities. Megalencephaly in fact could be associated with segmental overgrowth and cutaneous/vascular abnormalities (i.e., Proteus syndrome, CLOVES [congenital lipomatous overgrowth, vascular malformations, epidermal naevi, scoliosis, and/ or skeletal abnormalities] syndrome, Klippel-Trenaunay syndrome, megalencephaly-capillary malformation-polymicrogyria syndrome , megalencephaly-postaxial polydactyly-polymicrogyria-hydrocephalus syndrome, etc.) or generalized overgrowth (i.e., Weaver or Beckwith-Wiedemann syndrome) as well as with nanism in achondroplasia where megalencephaly is associated with disproportionate short stature, primary skeletal dysplasia, characteristic facies (prominent forehead, flat nasal bridge), narrow chest, and normal intelligence. It is possible to identify three main groups of disorders associated with megalencephaly: idiopathic or benign, metabolic, and anatomic. The idiopathic (benign) form indicates an abnormal increased head circumference in absence of neurological impairment, such as in benign familial megalencephaly. In metabolic megalencephaly (such as in organic acid disorders, metabolic leukoencephalopathies, or lysosomal diseases) there is an increase of different constituents that increase the size of the brain, whereas in the anatomical form there are underlying genetic causes. Neuroimaging is crucial for diagnosis, as it can reveal a generalized brain growth or a segmental one and possible specific frameworks associated. In all these conditions it is necessary to identify possible microdeletion-microduplication by chromosomal arrays.

Keywords

megalencephaly - hemimegalencephaly - macrocephaly - epilepsy - rehabilitation

* The authors contributed equally to the article.




Publication History

Received: 05 December 2023

Accepted: 04 April 2024

Article published online:
11 May 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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