A novel variant of Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy and hearing loss – a differential diagnosis in floppy infant syndrome

• Published in: Neuropediatrics
• Main Authors: Baumann, M, Giunta, C, Bönnemann, C, Quijano-Roy, S, Muntoni, F, Cirak, S, Schreiber, G, Bittner, R, Colombi, M, Rohrbach, M, Steinmann, B, Rostásy, K, Krabichler, B, Zschocke, J, Fauth, C
• Format: Conference Proceeding
• Language: English
• Published: 03.04.2012
• Subjects: hearing impairment; myopathy; Ehlers-Danlos syndrome
• ISSN: 0174-304X; 1439-1899
• DOI: 10.1055/s-0032-1307058

Aims: We report on a novel autosomal recessive variant of Ehlers-Danlos syndrome (EDS) characterized by severe muscle hypotonia at birth, delayed motor development, joint hypermobility, hyperelastic skin, progressive scoliosis, myopathy and sensorineural hearing impairment. Methods: The candidate gene was identified by linkage analysis in a large kindred of European descent and belongs to the family of FK506-binding proteins (FKBPs). FKBPs are involved in various biochemical processes including protein folding, protein trafficking and receptor signaling. Sequence analysis revealed a homozygous frameshift mutation in the candidate gene in all affected members of the index family. Results: Based on the cardinal clinical characteristics of the disorder four additional individuals originating from different European countries were identified who carried either homozygous or compound heterozygous mutations in the gene. All affected individuals presented with severe generalized hypotonia at birth and marked muscle weakness which improved in infancy. Motor development was delayed and reduced muscle strength persisted into adulthood. Signs of primary muscle disease were identified by muscle MRI, histology and electron microscopy. Characteristic symptoms like joint hypermobility, skin hyperelasticity and follicular hyperkeratosis, but also occasional features like bladder diverticula, inguinal or umbilical herniae and subdural hygroma, reveal systemic connective tissue involvement. Conclusion: Clinically the disorder shares many features with the kyphoscoliotic type of EDS (EDS VIA) and Ullrich congenital muscular dystrophy. Mutation analysis of this gene should be considered in all individuals with apparent kyphoscoliotic type of EDS and normal urinary pyridinoline excretion, in particular in conjunction with sensorineural hearing impairment. This novel disorder is a differential diagnosis to be considered in floppy infant syndrome and Ullrich congenital muscular dystrophy.