Abstract
We report an extremely rare case of combined classical and periodontal Ehlers−Danlos syndrome (EDS) with early severe periodontitis and a generalized lack of attached gingiva. A German family with classical EDS was investigated by physical and dental evaluation and exome and Sanger sequencing. Due to the specific periodontal phenotype in the affected child, an additional diagnosis of periodontal EDS was suspected. Physical and genetic examination of two affected and three unaffected family members revealed a family diagnosis of classical EDS with a heterozygous mutation in COL5A1 (c.1502del; p.Pro501Leufs*57). Additional to the major clinical criteria for classical EDS—generalized joint hypermobility, hyperelastic skin, and atrophic scarring —the child aged four years presented with generalized alveolar bone loss up to 80%, early loss of two lower incisors, severe gingival recession, and generalized lack of attached gingiva. Due to these clinical findings, an additional diagnosis of periodontal EDS was suspected. Further genetic analysis revealed the novel missense mutation c.658T>G (p.Cys220Gly) in C1R in a heterozygous state. Early severe periodontitis in association with generalized lack of attached gingiva is pathognomonic for periodontal EDS and led to the right clinical and genetic diagnosis in the present case.
Highlights
The Ehlers–Danlos syndromes (EDSs) comprise a clinically and genetically heterogeneous group of connective tissue disorders characterized by variable combinations of joint hypermobility, skin hyperextensibility, connective tissue fragility, and other manifestations
We report a unique case of classical EDS with a frameshift mutation in COL5A1 in a German family, combined with periodontal EDS caused by a de novo C1R in an almost five-year-old girl
Our case highlights the need to have an open mind with regard to the possibility of two independent monogenic conditions in the same individual
Summary
The Ehlers–Danlos syndromes (EDSs) comprise a clinically and genetically heterogeneous group of connective tissue disorders characterized by variable combinations of joint hypermobility, skin hyperextensibility, connective tissue fragility, and other manifestations.In 2017 the international EDS consortium published a revised classification system, “The2017 International Classification of the Ehlers–Danlos Syndromes” [1], which recognizes 13 distinct types of EDS caused by mutations in 19 different genes (the genetic basis of one relatively common type, hypermobile EDS, is unknown). Classical EDS (cEDS) is inherited in an autosomal-dominant pattern and is characterized by the major criteria hyperextensibility of the skin, atrophic scarring, and generalized. Due to the fragility of the skin, even relatively minor trauma can lead to bruising and cuts, especially over pressure points (knees, elbows, shins, forehead, and chin). Joint hypermobility affects both large and small joints, depending on age, gender, family, and ethnic background. According to the 2017 classification, classical EDS is clinically diagnosed when skin hyperextensibility and atrophic scarring is associated with either generalized joint hypermobility or at least three minor criteria [1]. The clinical diagnosis of cEDS can be confirmed by detection of a heterozygous pathogenic mutation in one of the genes encoding type V collagen (COL5A1 and COL5A2) in more than 90% of patients; rarely specific mutations in the genes encoding type I collagen (COL1A1 and COL1A2) are detected
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