Congenital Microcephaly: A Debate on Diagnostic Challenges and Etiological Paradigm of the Shift from Isolated/Non-Syndromic to Syndromic Microcephaly.
Cells
; 12(4)2023 02 16.
Article
en En
| MEDLINE
| ID: mdl-36831309
ABSTRACT
Congenital microcephaly (CM) exhibits broad clinical and genetic heterogeneity and is thus categorized into several subtypes. However, the recent bloom of disease-gene discoveries has revealed more overlaps than differences in the underlying genetic architecture for these clinical sub-categories, complicating the differential diagnosis. Moreover, the mechanism of the paradigm shift from a brain-restricted to a multi-organ phenotype is only vaguely understood. This review article highlights the critical factors considered while defining CM subtypes. It also presents possible arguments on long-standing questions of the brain-specific nature of CM caused by a dysfunction of the ubiquitously expressed proteins. We argue that brain-specific splicing events and organ-restricted protein expression may contribute in part to disparate clinical manifestations. We also highlight the role of genetic modifiers and de novo variants in the multi-organ phenotype of CM and emphasize their consideration in molecular characterization. This review thus attempts to expand our understanding of the phenotypic and etiological variability in CM and invites the development of more comprehensive guidelines.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Microcefalia
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
/
Guideline
Límite:
Humans
Idioma:
En
Revista:
Cells
Año:
2023
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
CH
/
SUIZA
/
SUÍÇA
/
SWITZERLAND