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

Abstract

Ehlers-Danlos syndrome type VIII (EDS-VIII) is a very rare autosomal dominant disease characterized by early-onset periodontitis associated with features of Ehlers-Danlos syndrome. We report a 32-year-old man whose chronic leg ulcer led to the diagnosis of EDS-VIII. He had severe periodontitis with complete loss of permanent teeth and skin fragility with thin skin, atrophic scars, and brownish atrophic pretibial plaques. Leg ulcer is not a prominent feature of EDS-VIII. We suggest adding EDS-VIII to the list of rare diseases accounting for chronic leg ulcers, if this case report prompts others to report leg ulcers associated with EDS-VIII.

Periodontal manifestations of Ehlers–Danlos syndromes: A systematic review

“…Risk of bias for one publication (Rahman et al., ) was assessed as moderate, due to missing concise clinical and periodontal case descriptions. Pedigree analyses including one family ( n = 5; with sample sizes ranging from 2 to 12 affected individuals) (Biesecker, Erickson, Glover, & Bonadio, ; Nelson & King, ; Reinstein, Pariani, Lachman, Nemec, & Rimoin, ; Reinstein, Wang, Zhan, Rimoin, & Wilcox, ; Reinstein et al., ). Quality of all pedigree analysis was assessed as good (low risk of bias). Case reports ( n = 23; with sample sizes of one to two affected individuals)(Apaydin, ; Bond, Friend, & Meridith, ; Buckel & Zaenglein, ; Chen, Lee, Yu, & Chiang, ; Cikla, Sadighi, Bauer, & Baskaya, ; Cunniff & Williamson‐Kruse, ; Dyne, Vitellaro‐Zuccarello, Bacchella, Lanzi, & Cetta, ; Flachowsky, Tolkendorf, & Kamin, ; George et al., ; Hartsfield & Kousseff, ; Hoffman et al., ; Karrer, Landthaler, & Schmalz, ,b; Linch & Acton, ; Mataix, Banuls, Munoz, Bermejo, & Climent, ; McKusick, ; Moore, Votava, Orlow, & Schaffer, ; Perez, Al‐Shammari, Giannobile, & Wang, ; Riedl, Lost, Pontz, & Schofer, ; Ronceray et al., ; Slootweg & Beemer, ; Spranger, Spranger, Kirchhof, & Steinmann, ; Stewart, Hollister, & Rimoin, ). In two cases, respectively, two articles described the same individuals (Bond et al., ; Cunniff & Williamson‐Kruse, ; Karrer et al., ,b).…”

A Chinese family with periodontal Ehlers–Danlos syndrome associated with missense mutation in the C1R gene

“…pEDS was recognized as a distinct EDS subtype by Stewart, Hollister, & Rimoin, (), and the disease is characterized by severe periodontitis with early‐onset disease and premature loss of teeth, hyperpigmented scarring of pretibial areas, easy bruising and joint hypermobility. pEDS is an exceedingly rare subtype with autosomal dominant inheritance; to our knowledge, to date, only 23 case reports (McKusick, ; Stewart et al., ; Linch & Acton, ; Slootweg & Beemer, ; Riedl, Lost, Pontz, & Schofer, ; Flachowsky, Tolkendorf, & Kamin, ; Hartsfield & Kousseff, ; Hoffman et al., ; Bond, Friend, & Meridith, ; Dyne, Vitellaro‐Zuccarello, Bacchella, Lanzi, & Cetta, ; Apaydin, ; Cunniff & Williamson‐Kruse, ; Spranger, Spranger, Kirchhof, & Steinmann, ; Karrer, Landthaler, & Schmalz, 2000a; &b; Perez, Al‐Shammari, Giannobile, & Wang, ; Chen, Lee, Yu, & Chiang, ; Moore, Votava, Orlow, & Schaffer, ; Buckel & Zaenglein, ; Mataix, Banuls, Munoz, Bermejo, & Climent, ; Ronceray et al., ; Cikla, Sadighi, Bauer, & Baskaya, ; George et al., ), five simple family pedigree analyses (Biesecker, Erickson, Glover, & Bonadio, ; Nelson & King, ; Reinstein, Pariani, Lachman, Nemec, & Rimoin, ; Reinstein, Wang, Zhan, Rimoin, & Wilcox, ; Reinstein et al., ) and two large‐scale pedigree analyses (five or 17 families: Rahman et al., ; Kapferer‐Seebacher et al., ) of pEDS have been reported. In 2003, a genetic linkage study conducted in a five‐generation family with pEDS established disease mutation with chromosome 12p13 (Rahman et al., ).…”

Phenotypic mimicry between periodontal and vascular Ehlers‐Danlos variants resolved by molecular genetic testing

“…2). Histopathology demonstrated granulomatous changes indicative of necrobiosis lipoidica, rather than the nonspecific features of pEDS plaques 2 . Molecular genetic studies demonstrated a heterozygous variant (c.582+59>A) in intron 6 of the C0L3A1 gene, pathogenic in two patients with vEDS, affecting splicing, resulting in the skipping of exon 6 (p.Gly177_Pro194del), confirming vEDS, with coincident nondiabetic necrobiosis lipoidica and extensive dental disease of non‐periodontal origin.…”