We report two children with Ehlers Danlos, kyphoscoliotic type confirmed by Lysyl Hydroxylase 1 deficiency due to bi-allelic PLOD1 mutations (kEDS-PLOD1) who were initially thought to have either a diagnosis of classical EDS (cEDS) or a neuromuscular disorder due to absence of (congenital) scoliosis. As the two patients reported here illustrate, patients with kEDS-PLOD1 do not always have a kyphoscoliosis present at birth or in the first year of life, neither do they necessarily develop kyphoscoliosis later in infancy. Using the past criteria for kEDS there was considerable overlap with the clinical diagnostic criteria for EDS classical type. In the patients reported here without (kypho) scoliosis this has delayed the diagnosis, which is unfortunate as the diagnosis of kEDS-PLOD1 results in a different recurrence risk and has management consequences. Interestingly, the new criteria for kEDS would not have prevented this diagnostic delay as congenital or early onset kyphoscoliosis (progressive or non-progressive) is deemed obligatory for the diagnosis of kEDS.Being aware of the limitations of clinical diagnostic criteria, we recommend that (i) in patients without a positive family history nor identified COL5A1/2 mutations, lysyl hydroxylase deficiency or biallelic PLOD1 mutations should be excluded before the diagnosis classical EDS can be made and (ii) PLOD1 and COL5A1/2 should be included in the same Next Generation Sequencing (NGS) gene panel.

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Persistent URL dx.doi.org/10.1016/j.ejmg.2017.07.011, hdl.handle.net/1765/101650
Journal European Journal of Medical Genetics
van Dijk, F.S, Mancini, G.M.S, Maugeri, A, & Cobben, J.M. (2017). Ehlers Danlos syndrome, kyphoscoliotic type due to Lysyl Hydroxylase 1 deficiency in two children without congenital or early onset kyphoscoliosis. European Journal of Medical Genetics, 60(10). doi:10.1016/j.ejmg.2017.07.011