Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Ehlers-Danlos Syndrome kyphoscoliotic Type (EDS type VIA) [Q79.6]

OMIM numbers: 225400, 153454 (PLOD1)

Dr. rer. nat. Karin Mayer

Scientific Background

EDS type VI (kyphoscoliotic type) is inherited in an autosomal recessive pattern. The incidence of this very rare type of EDS is estimated to be 1 in 100.000 newborns. Typical features are a fragile, hyperextensible skin with impaired wound healing, atrophic scarring and propensity for hematoma formation, a generalized hypermobility of the joints, muscle hypotonia at birth, and progressive scoliosis with an early onset. Microcornea is a frequent ocular finding. Scleral fragility may lead to rupture of the ocular globe after minor trauma.

In the majority of patients the disease is caused by mutations in the gene coding for the enzyme lysyl hydroxylase 1 (LH1) and is referred to as EDS type VIA. LH is responsible for the hydroxylysine-based pyridinoline cross-links of type I and type III collagen, which is mainly found in skeletal tissues. This again is a prerequisite for the cross linking of the collagen fibrils providing them tensile strength. Therefore under-hydroxylated collagen fibrils are severely impaired in their stability.

Lysyl hydroxylase 1 (LH) is encoded by the gene PLOD1 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1) on chromosome 1p36.3-36.2. So far it is the only gene known to cause LH1 deficiency if mutated. In total there are more than 30 different PLOD1 mutations known in patients with EDS type VIA, among them, with an allele frequency of 19%, a very common 8.9 kb duplication of seven exons.

A LH1 enzyme deficiency can also be detected by an increased cross link ratio of lysyl pyridinoline (LP) to hydroxylysyl pyridinoline (HP) in the urine.  

A clinical indistinguishable clinical picture in patients with unsuspicious LP/LH ratio in the urine and normal LH1 activity without PLOD1 mutations is referred to as EDS type VIB subtype. Currently EDS type VIB is not well defined. The EDS subtypes with DST14 deficiency, FKBP14 deficiency, EDS spondylocheiro dysplastic form (SCD-EDS) as well as the brittle cornea syndrome type 1 (BCS1) can be classified into this group.