Clinical phenotypes and molecular characterisation of three patients with Ehlers-Danlos syndrome type VII

Editor—The Ehlers-Danlos syndrome (EDS) is a diverse group of heritable connective tissue disorders whose primary clinical features include soft, hyperextensible skin, dystrophic scarring, easy bruising, and joint hypermobility.1 An initial classification defined 10 distinct types of EDS,1but with recent advances in our understanding of the molecular pathology a revised nosology with six types has been proposed.2 In the original classification, EDS type VII, a subgroup characterised by extreme joint laxity, was divided into three subtypes, EDS VIIA, VIIB, and VIIC.1 In the revised nosology EDS VIIA and B are combined as the arthrochalasia type of EDS2 and, because of significant differences in the clinical phenotypes and molecular pathology, are separated from EDS VIIC, which is now called the dermatosparaxis type of EDS. EDS VIIA and VIIB (arthrochalasia type) are autosomal dominant disorders and the patients present with bilateral congenital hip dislocations, extreme multiple joint laxity, and recurrent subluxations of both large and small joints. Thoracolumbar scoliosis, short stature, and muscle hypotonia are common features. EDS VIIC (dermatosparaxis type) is a rare autosomal recessive form and the patients present with generally lax, extremely fragile, redundant skin analogous to the animal disease dermatosparaxis,3 4 umbilical or inguinal hernias, blue sclerae, numerous palmar creases, and micrognathia. They develop joint laxity but without subluxations. Type I collagen is the major structural protein of the connective tissues affected in EDS VII. It is a heterotrimeric protein containing two α1(I) chains and one α2(I) chain, the products of the two genes COL1A1 and COL1A2 . It is initially synthesised as a precursor protein having additional peptide sequences (propeptides) at both ends of the molecule; these must be removed by specific proteolytic enzymes to generate the mature protein.5Failure to cleave the amino-terminal propeptides and subsequent lack …