Homozygous MFN2 variants causing severe antenatal encephalopathy with clumped mitochondria.

This article focuses on a novel case of severe antenatal encephalopathy linked to a homozygous deletion in the MFN2 gene, which encodes mitofusin 2, a mitochondrial outer membrane GTPase essential for mitochondrial fusion. The identified deletion causes exon 16 skipping, resulting in loss of key protein domains and altered membrane topology, leading to clustered mitochondria unable to fuse and severe deficiencies in mitochondrial respiratory chain complexes, particularly complex I. Clinically, the fetus exhibited profound central nervous system malformations including lissencephaly, polymicrogyria, and cerebellar atrophy, representing the first reported prenatal presentation of MFN2 deficiency with such severe CNS involvement. This case expands the phenotypic spectrum of MFN2-related disorders beyond the typical Charcot-Marie-Tooth disease type 2A and highlights the critical role of MFN2 in fetal brain development.