Oral characteristics in adult individuals with periodontal Ehlers-Danlos syndrome

Aim Periodontal Ehlers-Danlos syndrome (pEDS) is a monogenic type of Ehlers-Danlos syndrome characterized by periodontal destruction at a young age. The present study aimed to document the oral phenotype of pEDS based on prospective clinical investigations. Materials and Methods Thirty-five adult individuals from 13 families with a clinically and genetically confirmed diagnosis of pEDS underwent a systematic oral assessment. Results Periodontitis stage 3 or 4 or edentulism due to periodontal destruction were diagnosed in 94% of the individuals. First permanent tooth loss was reported at the age of 21.5 years (median; range 13–43 years). Deep periodontal pockets were infrequent, with 94% measuring <4 mm. However, there was increased clinical attachment loss (CAL) averaging 8 mm (range 4–13 mm), and the probability of being edentate between the age of 35 and 44 years was 28–47% compared with less than 0.25% of the general population. Radiographic anomalous findings were only found in a portion of subjects and consisted of fused roots of maxillary second molars (81%), root hypoplasia (57%), taurodontism (26%) and tooth rotation of premolars (67%). As such, radiographic findings are not considered common characteristics of pEDS. Conclusions Characteristic oral traits of pEDS in adults are severe CAL with shallow probing depths and marked gingival recession. This is complemented by a lack of attached gingiva. These indications need to be paralleled by genetic analyses to diagnose pEDS unambiguously

SLC13A5 is the second gene associated with Kohlschutter-Tonz syndrome

BACKGROUND: Kohlschutter-Tonz syndrome (KTZS) is a rare autosomal-recessive disease characterised by epileptic encephalopathy, intellectual disability and amelogenesis imperfecta (AI). It is frequently caused by biallelic mutations in ROGDI. Here, we report on individuals with ROGDI-negative KTZS carrying biallelic SLC13A5 mutations. METHODS: In the present cohort study, nine individuals from four families with the clinical diagnosis of KTZS and absence of ROGDI mutations as well as one patient with unexplained epileptic encephalopathy were investigated by clinical and dental evaluation, parametric linkage analysis (one family), and exome and/or Sanger sequencing. Dental histological investigations were performed on teeth from individuals with SLC13A5-associated and ROGDI-associated KTZS. RESULTS: Biallelic mutations in SLC13A5 were identified in 10 affected individuals. Epileptic encephalopathy usually presents in the neonatal and (less frequently) early infantile period. Yellowish to orange discolouration of both deciduous and permanent teeth, as well as wide interdental spaces and abnormal crown forms are major clinical signs of individuals with biallelic SLC13A5 mutations. Histological dental investigations confirmed the clinical diagnosis of hypoplastic AI. In comparison, the histological evaluation of a molar assessed from an individual with ROGDI-associated KTZS revealed hypocalcified AI. CONCLUSIONS: We conclude that SLC13A5 is the second major gene associated with the clinical diagnosis of KTZS, characterised by neonatal epileptic encephalopathy and hypoplastic AI. Careful clinical and dental delineation provides clues whether ROGDI or SLC13A5 is the causative gene. Hypersensitivity of teeth as well as high caries risk requires individual dental prophylaxis and attentive dental management

SLC13A5 is the second gene associated with Kohlschütter-Tönz syndrome.

BACKGROUND: Kohlschütter-Tönz syndrome (KTZS) is a rare autosomal-recessive disease characterised by epileptic encephalopathy, intellectual disability and amelogenesis imperfecta (AI). It is frequently caused by biallelic mutations in ROGDI. Here, we report on individuals with ROGDI-negative KTZS carrying biallelic SLC13A5 mutations. METHODS: In the present cohort study, nine individuals from four families with the clinical diagnosis of KTZS and absence of ROGDI mutations as well as one patient with unexplained epileptic encephalopathy were investigated by clinical and dental evaluation, parametric linkage analysis (one family), and exome and/or Sanger sequencing. Dental histological investigations were performed on teeth from individuals with SLC13A5-associated and ROGDI-associated KTZS. RESULTS: Biallelic mutations in SLC13A5 were identified in 10 affected individuals. Epileptic encephalopathy usually presents in the neonatal and (less frequently) early infantile period. Yellowish to orange discolouration of both deciduous and permanent teeth, as well as wide interdental spaces and abnormal crown forms are major clinical signs of individuals with biallelic SLC13A5 mutations. Histological dental investigations confirmed the clinical diagnosis of hypoplastic AI. In comparison, the histological evaluation of a molar assessed from an individual with ROGDI-associated KTZS revealed hypocalcified AI. CONCLUSIONS: We conclude that SLC13A5 is the second major gene associated with the clinical diagnosis of KTZS, characterised by neonatal epileptic encephalopathy and hypoplastic AI. Careful clinical and dental delineation provides clues whether ROGDI or SLC13A5 is the causative gene. Hypersensitivity of teeth as well as high caries risk requires individual dental prophylaxis and attentive dental management.journal article2017 Jan2016 09 06importe

The 2017 international classification of the Ehlers-Danlos syndromes.

Item does not contain fulltextThe Ehlers-Danlos syndromes (EDS) are a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs) characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Over the past two decades, the Villefranche Nosology, which delineated six subtypes, has been widely used as the standard for clinical diagnosis of EDS. For most of these subtypes, mutations had been identified in collagen-encoding genes, or in genes encoding collagen-modifying enzymes. Since its publication in 1998, a whole spectrum of novel EDS subtypes has been described, and mutations have been identified in an array of novel genes. The International EDS Consortium proposes a revised EDS classification, which recognizes 13 subtypes. For each of the subtypes, we propose a set of clinical criteria that are suggestive for the diagnosis. However, in view of the vast genetic heterogeneity and phenotypic variability of the EDS subtypes, and the clinical overlap between EDS subtypes, but also with other HCTDs, the definite diagnosis of all EDS subtypes, except for the hypermobile type, relies on molecular confirmation with identification of (a) causative genetic variant(s). We also revised the clinical criteria for hypermobile EDS in order to allow for a better distinction from other joint hypermobility disorders. To satisfy research needs, we also propose a pathogenetic scheme, that regroups EDS subtypes for which the causative proteins function within the same pathway. We hope that the revised International EDS Classification will serve as a new standard for the diagnosis of EDS and will provide a framework for future research purposes. (c) 2017 Wiley Periodicals, Inc.01 maart 201