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Journal of Pediatric Neurology 2024; 22(02): 140-148
DOI: 10.1055/s-0044-1786776
Review Article

Microcephaly and Its Related Syndromes: Classification, Genetic, Clinical, and Rehabilitative Considerations

Alessandra Di Nora   *
1   Pediatrics Postgraduate Residency Program, University of Catania, Catania, Italy
,
Daria La Cognata   *
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
,
Michele Vecchio
3   Rehabilitation Unit, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
,
Rita Chiaramonte
3   Rehabilitation Unit, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
,
Francesco Marino
4   Department of Medical Surgical Sciences and Advanced Technologies, University Hospital Policlinico “G. Rodolico-San Marco,” Catania, Italy
,
Stefano Palmucci
5   IPTRA Unit, Department of Medical Surgical Sciences and Advanced Technologies, University Hospital Policlinico “G. Rodolico-San Marco,” Catania, Italy
,
Giuseppe Belfiore
6   Department of Medical Surgical Sciences and Advanced Technologies, Unit of Radiology I University Hospital Policlinico “G. Rodolico-San Marco,” Catania, Italy
,
Agata Polizzi
7   Chair of Pediatrics, Department of Educational Sciences, University of Catania, Catania, Italy
,
Andrea D. Praticò
8   Chair of Pediatrics, Department of Medicine and Surgery, Kore University, Enna, Italy
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Abstract

Microcephaly, a form of cortical cortex malformation, results from abnormal cellular production and proliferation, identified when the occipital frontal head circumference (OFC) falls two or more standard deviations (SDs) below the expected average for age, gender, and population. Severity is classified based on SD: mild (OFC < 2 SD) or severe (OFC < 3 SD). While microcephaly can lead to developmental delay, intellectual disability, epilepsy, and cerebral palsy, not all cases exhibit these issues. Classified as primary/congenital or secondary/postnatal, microcephaly can stem from genetic or acquired factors in both types. Congenital microcephaly origins vary, while secondary microcephaly is characterized by normal OFC at birth, followed by a decrease within the first year, often associated with progressive cognitive and motor impairments. Primary hereditary microcephaly (MCPH), or microcephaly vera, is genetically diverse, with 28 related genes (MCPH1 to MCPH28) encoding proteins linked to centrosomes and progenitor cell mitosis in the brain ventricle's neuroepithelium. Defects in deoxyribonucleic acid (DNA) repair pathways (e.g., NBN, FANCA, ATR, ATM genes) can lead to microcephaly by impairing DNA repair. Enzyme deficiencies in metabolic pathways may also contribute, causing toxic metabolite accumulation or essential metabolite loss (microcephaly of metabolic origin). Acquired congenital microcephaly may result from ischemic or infectious processes, drugs, radiation, maternal diseases during pregnancy, with damage influenced by fetal genetics, environmental interactions, developmental stage, and exposure intensity/duration. Diagnostic workup includes electroencephalogram, ophthalmological, auditory, magnetic resonance imaging, metabolic, echocardiogram, and infection screening tests, alongside genetic evaluations like cytogenetic studies, fluorescence in situ hybridization, comparative genomic microarray-hybridization, single-nucleotide microarray-polymorphism, and exome sequencing. Symptomatic treatment is available, and genetic counseling is crucial for affected families.

Keywords

microcephaly - brain malformations - genetics - causes - childhood

* These authors contributed equally to this article.




Publication History

Received: 11 December 2023

Accepted: 03 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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