Rare Genetic Disorders Affecting the Periodontal Supporting Tissues in Adolescence

Abstract

In adolescents periodontal destruction may be the primary manifestation of an as yet unrecognized rare systemic disease, and it may be up to the periodontist to make the correct tentative diagnosis. Many genetic diseases that present with primary periodontal manifestations in adolescence affect immune function, sometimes with only mild or absent systemic features. They include periodontal Ehlers-Danlos syndrome (lack of attached gingiva, various connective tissue abnormalities), Papillon-Lefèvre syndrome (palmoplantar hyperkeratosis), and plasminogen deficiency (fibrin deposition within mucous membranes). Other immune disorders with severe periodontitis manifesting in adolescence are usually diagnosed in early childhood due to unmistakeable systemic features. They include Cohen syndrome (developmental disorder, truncal obesity, and microcephaly), Hermansky-Pudlak Syndrome (oculocutaneous albinism, bleeding diathesis, and other systemic manifestations), glycogen storage disease type 1b, and Chediak-Higashi syndrome (pyogenic infections, albinism, and neuropathy). The structural integrity of periodontal tissue is affected in genodermatoses such as Kindler syndrome, a type of epidermolysis bullosa. In primary hyperoxaluria, inflammatory periodontal destruction is associated with renal calculi. Breakdown of periodontal tissues independent of dental plaque biofilm-induced periodontitis is found in hypophosphatasia (highly variable skeletal hypomineralization) or isolated odontohypophosphatasia, hypophosphatemic rickets and primary hyperparathyroidism. Finally, alveolar osteolysis mimicking localized periodontitis may be due to neoplastic processes, e.g., in neurofibromatosis type 1 (typical skin features including café au lait macules and neurofibromas), Langerhans cell histiocytosis (locally destructive proliferation of bone marrow-derived immature myeloid dendritic cells), and Gorham-Stout disease (diffuse cystic angiomatosis of bone).

Periodontal Treatment of Norwegian Patients With Rare Diseases: A Commentary

“…The first point was assessed by a number of RDs which had been presented in major review articles including glycogenesis, Papillon-Lefèvre syndrome, neutropaenia, Wegener's granulomatosis, hypophosphatemic rickets, Ehlers-Danlos syndrome, and epidermolysis bullosa dystrophic. 7 , 8 These all received higher levels of treatment in the present study. In addition, the study also combined the levels of periodontal treatment with the levels of treatment performed by periodontal specialists to identify the RDs with more severe periodontal complications.…”

“…The mechanisms behind the periodontal complications in RDs are mainly related to immunologic disorders, disorders of bone metabolism, neoplastic diseases, and diseases that affect the oral mucosa and gingival tissues. 7 , 8 The most common immunologic disorders are Papillon-Lefèvre syndrome, Ehlers-Danlos syndrome, plasminogen deficiency, Cohen syndrome, and neutropenia. Diseases involving bone metabolism include hypophosphatasia, hyperparathyroidism, and hypophosphatemic rickets.…”

“…Most of the information on the periodontal problems in RDs is obtained from case reports and narrative reviews. 7 , 8 Since these case reports and reviews report nearly exclusively on cases which have periodontal complications, it gives the impression that most or all patients with certain RDs should expect complications. It is not known how many of the RDs need periodontal treatment, nor is it known whether all patients within a certain RD group need treatment.…”

The Physiological and Pathological Role of Tissue Nonspecific Alkaline Phosphatase beyond Mineralization

“…Circulating TNAP exert an anti-inflammatory role by contributing to the generation of adenosine from AMP, detoxification by LPS dephosphorylation and regulating postprandial endotoxaemia [ 130 , 131 ]. In the HPP model with TNAP deficiency, bone marrow edema [ 132 ], osteomyelitis [ 133 ], tendinitis [ 134 ] and increased predisposition to periodontitis is widely seen among both children and adults [ 135 ]. TNAP through its ectonucleotidase activity exerts a major role in balancing pro-inflammatory ATP levels and anti-inflammatory role through adenosine, a breakdown product of ATP [ 136 ].…”

Epigenetics in susceptibility, progression, and diagnosis of periodontitis

“…A small portion of periodontitis patients possesses severe phenotypes from prepubertal or adolescent age, and this type of periodontitis is called aggressive periodontitis (AP) or early-onset periodontitis; however, CP and AP phenotypes are currently characterized by the same indicators, using a multi-dimensional staging and grading system [10] , [11] . Periodontal diseases also develop as one of the manifestations of systemic genetic disorders, such as immunologic disorders, which include Papillon-Lefèvre syndrome, Chediak-Higashi syndrome, Cohen syndrome, and Ehlers-Danlos syndrome, and bone metabolism disorders such as hypophosphatasia [12] . These clinical observations suggest that genetic and epigenetic factors have predominant roles for the development of periodontitis.…”