Arthrogryposis multiplex congenita (AMC) is a heterogeneous group of congenital disorders characterized by multiple joint contractures. We report a family with two children affected with AMC. First child had a severe AMC phenotype and died in infancy. Second child, currently 4-years-old, was ascertained at the age of 30 months with mild AMC phenotype with cognitive and speech delay. On whole exome sequencing, a novel biallelic sequence variant in initiation codon of LGI4 (leucine-rich glioma-inactivated 4) gene was identified in her. Real-Time PCR revealed 50% reduction in mRNA transcript levels in subject as compared to control which explains the milder phenotype. Till date, only four families with nine affected individuals with LGI4-related AMC have been reported. Except for one child surviving up to 6 years, all others were either terminated after prenatal diagnosis or succumbed in neonatal period. This study adds to mutation spectrum of LGI4 and reports the second case of mild AMC with extended phenotype. We review the existing phenotypic and genotypic information for the individuals with this condition and highlight the intrafamilial and interfamilial variability in these individuals.
Keywords: Arthrogryposis multiplex congenita; Initiation codon; Leucine-rich glioma-inactivated 4; Myelin; Whole exome sequencing.
Copyright © 2019 Elsevier Masson SAS. All rights reserved.