*5.2.1.1 Marfan syndrome*

Mutation of a gene encoding for fibril-1 present in chromosome 15 marks a defect in the synthesis of a glycoprotein forming part of the connective tissue matrix. This causes defects in a series of locations such as the ocular lens suspensory ligament, blood vessel walls and, apparently, the periodontal ligament [62].

Periodontal manifestations:

The mode of periodontal pathogenesis in these syndromes can be understood by connective tissue modifications which generates increased vulnerability to periodontal inflammation and bone resorption. Despite the co-existence of a similar background alteration, the manifestations of periodontal disease vary in their presentation in each of the syndromes. For instance, Marfan syndrome exhibit both chronic and severe form of disease with patterns of horizontal and vertical bone resorption, in accordance to the presence of bacterial plaque. However, tooth mobility has been shown to be a sequel to periodontitis, and is not endorsed to the primary condition of the syndrome [62, 63].

#### *5.2.1.2 Ehler-Danlos syndrome*

Ehlers-Danlos syndrome (EDS) comprises a group of genetic diseases involving the connective tissue characterised by mutations in the genes responsible for the collagen biosynthesis. The clinical expressions of EDS include increased tissue fragility, hypermobility of joints, and hyperextensibility of skin [64].

Periodontal manifestations

In EDS, periodontal disease can be linked with syndromes type I, VII, III, or IV. Type I EDS has *increased predisposition to periodontal disease, whereas type VIII manifests as early onset periodontitis, with premature loss of permanent teeth, fragility of the mucosa leading to bleeding gums and oral mucosa The postulated mechanism is a defect in type III collagen, amounting to a total of periodontal junction. Moreover, a relationship has been found to Fusobacterium nucleatum, which could be isolated from the active affected sites* [65].

### *5.2.2 Immune related conditions*

The immune conditions contemplated in the above classification are all primary immune deficiencies caused by a decrease in neutrophil presence, or by modifications in the functions of these cells – as in the above cited syndromes. These conditions predispose patients to bacterial and fungal infections in childhood, because the decrease in neutrophil presence alters the host defence capacity. Additionally, a drop is seen in the production of granulocyte colony stimulating factors [66, 67]. Let us discuss some significant disorders.

#### *5.2.2.1 Chediak-Higiashi syndrome*

Chediak-Higiashi syndrome is supplemented by leukocyte modification, basically limited to the lysosomes, which destroy melanosomes producing oculocutaneous albinism. Affected patients also present mental retardation, and neutropenia additionally may also be observed – with altered LA.

#### *5.2.2.2 Down syndrome*

Down syndrome or trisomy 21 results because of chromosomal abnormality that causes peculiar physical changes, with co-existing mental retardation and other systemic alterations. The immune changes described in Down syndrome are linked to function of WBCs, responsible for the defensive mechanisms in periodontal tissues [68, 69].

### *5.2.2.3 Papillon-Lefèvre syndrome*

Papillon-Lefèvre syndrome is classically manifested as palmoplantar erythematous hyperkeratosis along with periodontal disease. The proposed mechanism is linked to a mutation of the gene encoding for cathepsin C, which generates a lysosomal protein implicated to modify the host immune response, inflammatory response and extracellular matrix function with significant changes in the palmar, plantar and gingival epithelium [64]. Hyperimmunoglobulinemia E (HE) consists of an increase in serum immunoglobulin E (IgE). This in turn leads to a series of systematic variations with involvement of the skin, facial malformations and increased vulnerability to staphylococcal infections [70, 71].

#### **5.3 Periodontal manifestations of immune related disorders**

In neutrophil disorders, the notable reduction in the amount of neutrophils tends to disregulate the host defence capacity, causing periodontal disease to manifest at a younger age. Gingival inflammation, aggressive periodontal tissue destruction, edema, pocket formation and tooth mobility are common presentations. This clinical representation is much similar to prepuberal or rapidly progressive periodontitis with premature loss of the deciduous teeth [66, 68, 72].

#### *5.3.1 Chediak-Higiashi syndrome*

Chediak-Higiashi syndrome manifests as early occurrence of periodontitis with premature exfoliation of both dentitions. The bone resorption patterns may be local or generalised, and are linked to associated inflammation. The disorder is associated with anaerobic flora, due to the amble presence of purulent processes. The abundant presence of spirochetes in the locations with inflammation and high proteolytic activity, which facilitates bacterial adherence further explains the pathosis. Adding to this, the co-existence of lysosomal modifications and defective chemotaxis in neutrophils gives rise to very rapidly progressing periodontitis that inclines to be recurrent and is refractory to antibiotic treatment [68].

#### *5.3.2 Down syndrome*

Down syndrome is characterised by aggressive and generalised periodontitis, with subsequent damage of the supporting tissues and loss of teeth at an early age. Eight percent of Down syndrome children suffer periodontal lesions by 12 years of age [73]. The rate of occurence of periodontal disease in this population ranges from 60–100% in young adults under 30 years of age [70]. The co existence of immune deficiency, inadequate control of bacterial plaque, deficient masticatory function, early ageing and alterations in dental anatomy (short roots) predispose or aggravate the progression of periodontal disease [74, 75].

In patients with higher level of mental retardation, difficulties are observed with relation to oral hygiene maintenance. Oral health care needs to be emphasised



#### **Table 5.**

*Comprehensive tabulation of genetic disorders and their periodontal manifestations [44, 61, 62].*

in order to avoid the accumulation of plaque leading to initiation of the disease [76–78]. The presence of defective neutrophil chemotaxis, leads to progressive periodontitis as observed in juvenile periodontitis. Concurrently, it has been reported that the B cells,T cells, and monocytes, also illustrate functional defects. The periodontal destruction is directly proportional to the degree of alteration in

functional chemotaxis. The mechanism mounting for the dysfunction is attributed to a decrease in the number of cell surface receptors, and diminished levels of zinc and some vitamins in serum [70].
