Abstract
Background
Ehlers-Danlos syndrome (EDS) represents a group of connective tissue disorders characterized by the fragility of the soft connective tissues resulting in widespread skin, ligament, joint, blood vessel and internal organ involvement. The clinical spectrum is highly variable in terms of clinical features, complications, severity, biochemical characteristics and genes mutations.
The kyphoscoliotic type EDS (EDS VIA) is a rare variant of the disease, with an incidence of 1:100.000 live births. EDS VIA presents at birth as severe muscular hypotonia, early onset of progressive kyphoscoliosis, marked hyperelasticity and fragility of the skin with abnormal scarring, severe joint hypermobility, luxations and osteopenia without a tendency to fractures. This condition is due to a mutation in the PLOD1 gene, and less commonly in FKBP14 gene, which results in the erroneous development of collagen molecules with consequent mechanical instability of the affected tissue.
Case presentation
A female newborn, found to be floppy at birth, presented a remarkable physical examination for joint hypermobility, muscle weakness, hyperelastic skin, a slight curve of the spine, the absence of the inferior labial and lingual frenulum. Due to severe hypotonia, neuromuscular disorders such as Spinal Muscular Atrophy (SMA), genetic diseases such as Prader Willi syndrome (PWS), myopathies and connective tissue disorders were considered in the differential diagnosis. Targeted gene sequencing were performed for SMN1, PLOD1, FKBP14, COL6A1, COL6A2, COL6A3. The urinary lysyl and hydroxy-lysyl pyridinoline ratio was diagnostic before discovering the homozygous duplication in the PLOD1 gene, which confirmed kyphoscoliotic EDS diagnosis.
Conclusion
In front of a floppy infant, a large variety of disorders should be considered, including some connective diseases. The presence at the birth of kyphoscoliosis, associated with joint hypermobility and the absence of the lingual and lower lip frenulum, should suggest an EDS.
Mutations in FKBP14 Cause a Variant of Ehlers-Danlos Syndrome with Progressive Kyphoscoliosis, Myopathy, and Hearing Loss
