Ehlers-Danlos syndrome: an important differential diagnosis for congenital myopathies

Abstract

Kyphoscoliotic Ehlers-Danlos syndrome (kEDS) is a genetic collagen disorder, with early onset hypotonia, weakness, progressive kyphoscoliosis, joint hypermobility, and other features underlying connective tissue involvement. On the other hand, congenital myopathies (CMs) are genetic muscle disorders, with hypotonia and weakness usually from birth which can associate with skeletal deformities. Case 1: RSS, 2-year-old, male. At birth, hip dysplasia and global hypotonia. On examination, proximal tetraparesis, global hyporeflexia and hypotonia, joint hypermobility, ogival palate, umbilical hernia, scoliosis and clubfoot. Genetic testing: Homozygous pathogenic variant in the FKBP14 gene (ENST0000000222803- c.362_363insC, p.Glu122Argfs*7), associated with kEDS type II. Case 2: RRO, 37-year-old, female. Global hypotonia at birth with congenital hip dislocation. On examination, mild proximal weakness, global hyporeflexia, joint hypermobility, scoliosis and ogival palate. Absence of marfanoid habitus. Genetic testing: Homozygous pathogenic variant in the PLOD1 gene (ENST00000196061-c.2032G>A, p.Gly678Arg), associated with kEDS type I. Conclusion: Uncommon clinical features in CMs should alert for an alternative diagnosis. Extreme joint laxity is more often a sign of a connective tissue disease, and can be associated with Marfanoid habitus, arterial dissection, bluish sclerae, umbilical hernia. Both patients presented nonspecific findings like neonatal skeletal deformities, hypermobility and mild weakness. A wide genetic test was definitive for the correct diagnosis. EDS must be included in the differential diagnosis of congenital myopathies, especially when associated with involvement of connective tissue. This is very relevant in the management care of the patients.