Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA): clinical, molecular and biochemical delineation

We describe the clinical, biochemical and molecular characterisation, as well as electron microscopy findings of skin, in 15 patients newly diagnosed with this rare type of Ehlers-Danlos syndrome.Age at diagnosis ranged from 5 months to 27 years, with only 1/3 of the patients been diagnosed correctly in the first year of life. A similar disease frequency was found in females and males, however a broad disease severity spectrum (intra- and interfamilial), independent of molecular background or biochemical phenotype, was observed. Kyphoscoliosis, one of the main clinical features was not present at birth in 4 patients. Importantly we also noted the occurrence of vascular rupture antenatally and postnatally, as well as developmental delay in 5 patients.In view of these findings we propose that EDS VIA is a highly variable clinical entity, presenting with a broad clinical spectrum, which may also be associated with cognitive delay and an increased risk for vascular events. Genotype/phenotype association studies and additional molecular investigations in more extended EDS VIA populations will be necessary to further elucidate the cause of the variability of the disease severity.The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS), type VIA (MIM 225400) is a rare autosomal recessively inherited connective tissue disorder with a disease incidence of approximately 1;100,000 live births. The disorder is characterized at birth by severe muscular hypotonia often requiring invasive neuromuscular work-up, kyphoscoliosis which is progressive and severe, marked joint hypermobility and luxations, and severe skin hyperelasticity. In addition, there is fragility of the skin with abnormal scarring, osteopenia without tendency to fractures, often a striking Marfanoid habitus and microcornea, bluish sclera, and occasionally rupture of arteries and the eye globe, in contrast to rupture of the cornea reported in brittle cornea syndrome [1-3]. Intellect is reportedly unaffected.The kyph