Possible founder variant and spectrum of phenotypic manifestations of Fukuyama congenital muscular dystrophy in five unrelated families in Pakistan: A case series

Abstract

Fukuyama congenital muscular dystrophy (FCMD) is a rare autosomal recessive dystroglycanopathy caused by pathogenic/likely pathogenic (P/LP) variants also known as mutations in the FKTN gene, typically presenting in early childhood with hypotonia, progressive muscle weakness, and variable central nervous system and cardiac involvement. This case series describes five male patients from consanguineous families in different regions of Pakistan, all presenting with features of a progressive muscular dystrophy. Genetic analysis revealed a homozygous pathogenic missense variant, FKTN, NM_001079802.1 c.920G>A (p.R307Q), in all five patients, suggesting the presence of a possible founder variant. Despite sharing the same genetic mutation, the patients exhibited significant clinical heterogeneity. This report adds to the limited literature on FCMD in South Asia and emphasizes the phenotypic variability of the disorder, particularly its cardiac manifestations. The development of cardiomyopathy is not uncommon, hence regular cardiac monitoring is crucial. Early genetic diagnosis is vital for appropriate clinical management and genetic counseling in populations with high rates of consanguinity.