Prepubertal Periodontitis in a Patient with Combined Classical and Periodontal Ehlers–Danlos Syndrome

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.

A case of early-onset periodontitis with vitamin D deficiency: A case report and literature review

“…Polymorphisms of BRAF V600E and TNSALP, autosomal genetic variation and some other syndromes are common factors for early-onset periodontitis (Table 1). [20][21][22][23][24][25][26][27][28][29] Nonetheless, we commonly ignore the roles of nutrition in the onset and development of periodontitis. In this case, the patient's systemic examination report showed deficient vitamin D levels with no other abnormalities.…”

“…Qi [16] 2021 Vitamin D deficiency 5 Movement and loss of partial teeth and deep periodontal pockets of remaining teeth Low vitamin D level Deciduous Vitamin D receptor gene mutant Stock [24] 2021 Ehlers-Danlos Syndrome 5 Severe gingival recession and significant alveolar bone loss Joint hypermobility, skin hyperextensibility and connective tissue fragility Deciduous Autosomal dominant genetic Chew [26] 2020 Maturity onset diabetes 21 Multiple periodontal abscesses and severe dental fluorosis…”

Oral manifestations of Ehlers‐Danlos syndromes

“…Two recent pedigree analyses confirm that severe early onset periodontitis is a distinguishing feature between pEDS and classical EDS (cEDS) or vascular EDS (vEDS). In one case, a child with cEDS displayed periodontal bone loss in the primary dentition and a gingival phenotype specific for pEDS (Stock et al, 2021 ). The genetic analysis elucidated two pathogenic mutations, a COL5A1 mutation causative of cEDS together with a de novo C1R mutation causative of pEDS.…”

Oral characteristics in adult individuals with periodontal Ehlers‐Danlos syndrome

“…Since the first reports of pEDS in the 1970s (McKusick, 1972 ; Stewart et al, 1977 ), 38 case reports/series, seven pedigree analyses and two cohort studies describing a total of 165 individuals have been published (Cortés‐Bretón Brinkmann et al, 2021 ; Kapferer‐Seebacher et al, 2017 , 2019 ; Wu et al, 2018 ; Seo et al, 2019 ; El Chehadeh et al, 2021 ; Stock et al, 2021 ; Nakajima et al, 2022 ). Importantly, all authors reported severe periodontitis as a major criterion of pEDS.…”