Ehlers–Danlos syndrome type VIII is clinically heterogeneous disorder associated primarily with periodontal disease, and variable connective tissue features

Abstract

We would like to dedicate this article to the memory of David Rimoin, MD, PhD, who passed away on May 27, 2012. He was an outstanding geneticist, mentor, and human being.Ehlers-Danlos syndrome (EDS) type VIII (periodontitis type) is a distinct form of EDS characterized by periodontal disease leading to precocious dental loss and a spectrum of joint and skin manifestations. EDS type VIII is transmitted in an autosomal dominant pattern; however, the mutated gene has not been identified. There are insufficient data on the spectrum of clinical manifestations and natural history of the disorder, and only a limited number of patients and pedigrees with this condition have been reported. We present a four-generation EDS type VIII kindred and show that EDS VIII is clinically variable and although some cases lack the associated skin and joint manifestations, microscopic evidence of collagen disorganization is detectable. We further propose that the diagnosis of EDS type VIII should be considered in familial forms of periodontitis, even when the associated skin and joint manifestations are unconvincing for the diagnosis of a connective tissue disorder. This novel observation highlights the uncertainty of using connective tissue signs in clinical practice to diagnose EDS type VIII.

Ehlers-Danlos Syndrome Type VIII: A Rare Cause of Leg Ulcers in Young Patients

“…Other inconstant features of EDS-VIII, such as a marfanoid habitus, a characteristic triangular facies, minimal skin hyperextensibility, and moderate joint hypermobility, were not present. The same periodontal disease in his mother reinforced the hypothesis of a hereditary disease, and other causes of autosomal dominant periodontitis were ruled out [3, 4]. Morphological abnormalities of collagen were observed in our patient's skin.…”

“…Interpretation of these plaques as simple stasis dermatitis [10] does not fully account for their clinical characteristics. Indeed, as in our patient, their clinical features are the brownish color, the atrophic aspect, the well-circumscribed border, and the atypical topography on pretibial areas [2–4, 6]. Pathological examination of skin biopsies from these lesions revealed nonspecific dermal fibrosis and hemosiderin deposition [2].…”

“…Although they may not be present in some families of EDS-VIII [9], they seem to be a pervasive feature since the first description in 1972 [1]. They are thought to be a result of extensive bruising and confluent atrophic scars because of the increased fragility of dermis and small blood vessels [4]. Interpretation of these plaques as simple stasis dermatitis [10] does not fully account for their clinical characteristics.…”

Ehlers–Danlos syndrome: A cause of epilepsy and periventricular heterotopia

“…32 To date, this is the only confirmed X-linked form of EDS. Recently, Reinstein et al 33 have suggested that there is little molecular or clinical justification for considering EDS-PH as a separate entity from XL-PH, but instead they proposed that there is a spectrum of vascular and connective tissues anomalies associated with this condition for which all individuals with loss-offunction mutations in FLNA should be evaluated.…”

“…The skeletal phenotypes include joint laxity and dislocations, Marfanoid habitus, osteopenia, early-onset osteoarthritis, pectus deformity, scoliosis and pes planus. 33 …”