Periodontitis Associated with Genetic Disorders Today, I want to talk about the periodontitis that results from genetic disorders. There are various genetic disorders that are associated with periodontitis but I will limit my presentation to the eight most common ones. Welcome to my presentation.

Introduction Periodontal diseases refers to inflammation of the structures that support the teeth. They are caused by periodontopathic bacterial resulting in progressive loss and destruction of periodontium. This leads to tooth loss. They are caused by a host of different factors, one of them being diseases Periodontal diseases refers to inflammation of the structures that support the teeth. They are caused by periodontopathic bacterial resulting in progressive loss and destruction of periodontium. This leads to tooth loss. They are caused by a host of different factors, one of them being diseases. As shown in the figure, periodontitis affects the gums which pull away as a result of tartar leaving the roots exposed. The affected structures include gingiva, alveolar tissues, ligaments, and cementum The end result is loose teeth.

Cyclic Neutropenia  Disorder that causes infection leading to shortage of neutrophils (white blood cells). Reduced neutrophils lowers the immune system Infections in sinuses, respiratory tract, and skin, Mouth Sores, gingivitis etc. Cyclic neutropenia can be described as a disorder that mainly causes recurrence infections and a host of health problems that leads to a shortage of neutrophils, a type of white blood cells that fights infection and inflammation. Neutropenia may occur at birth or shortly afterwards, recurring after every 21 days and lasting for three to five days. Lack of white blood cells make it difficult for the body to fight bacteria and viruses leading to recurrent infections in sinuses, respiratory tract, and skin, ulcers in the mouth, gingivitis, and many others. Source: https://ghr.nlm.nih.gov/condition/cyclic-neutropenia#diagnosis

As can be seen in this image, a neutropenia destroys the periodontium As can be seen in this image, a neutropenia destroys the periodontium. The accumulation of bacteria leads to infection, most commonly being the acute necrotizing gingivitis lessons. Mouth sores (ulcers) are common in this case because of uncontrolled growth of bacteria in the mouth.   Source: http://www.slideshare.net/DrmanjuPriya/gingivitis-9628801

Down Syndrome Periodontitis is a commonly problem in Down syndrome Estimated prevalence between 58% and 96% for those under 35 years of age Periodontitis is a commonly problem in Down syndrome, one of the most common genetic disorders. The specific characteristics of Down syndrome like reduced production of saliva are one of the predisposing factors to periodontitis. There is a strong relationship between periodontitis and Down syndrome with an estimated prevalence between 58% and 96% for those under 35 years of age. Sorce: Khocht (2011)

Pathway: This image shows the collective sequential events in the pathogenesis of periodontitis in DS patients. There is decreased flow of saliva accompanied by low salivary antibody production and a defective neutrophil chemotaxis provides for early microbial colonization, making it possible for periodontal pathogens to grow. High microbial presence leads to a strong gingival immune/inflammatory response that is characterized by a high levels of macrophages and lymphocytes in the gingival tissues. The antigens respond by producing antibodies while macrophages and gingival residents cells are engaged in production of degrading enzymes. In frustration, neutrophils are likely to produce degrading enzymes extracellular into the gingival tissues leading to tissue injury. Tissue injury leads to release of arachidonic acid metabolites (prostaglandins) which are involved in periodontal issues destruction.

Leukocyte Adhesion Deficiency Syndrome LAD is a rare genetic disorder Inherited disease through immunodeficiency at birth Caused by failure to express cell – surface integrin (CD18) that is important for leukocytes adherence to vessel wall at the infection site. Causes infection like otitis media, primary and permanent tooth loss LAD is a rare genetic disorder that is caused by autosomal recession. It is mainly characterized by defect that is associated with white blood cells resulting in a defective phagocytic function. This leads to poor leukocyte migration on the infection site, impaired function of the leukocyte and increased risk of infection including periodontitis. It is an inherited disease through immunodeficiency at birth due to failure to express cell – surface integrin (CD18) that is important for leukocytes adherence to vessel wall at the infection site. Children with the condition have a recurrent infection like otitis media, primary and permanent tooth loss.   Source: Garcia et al. (2011)

a. Gingival inflammation b. Severe bone loss The pathological manifestation of LAD in periodontitis is mainly due to severe chronic infection. As shown in this image, severe periodontitis is present that leads to severe loss of the alveolar bone. The early-onset periodontitis in the primary dentition and the alveolar bone loss in the primary teeth is mainly due to early exfoliation of the entire dentition. Gingival inflammation is present is present in the affected teeth, in both primary and permanent dentition as shown in figure a, while figure b. shows severe bone loss as a result. Source: http://pocketdentistry.com/conditions-associated-with-premature-exfoliation-of-primary-teeth-or-delayed-eruption-of-permanent-teeth/

Papillon Lefévre Syndrome Papillon-Lefevre syndrome is mainly caused by gene mutation in the cathespin C gene which functions by coding for a protein and playing an important role in the immune cells. Mainly manifested in the hyperkeratosis of the palms of the hands (a) and soles of the feet (b). The etiology follows an autosomal recessive pattern of inheritance with a prevalence of four per million live births. Papillon-Lefevre syndrome is mainly caused by gene mutation in the cathespin C gene which functions by coding for a protein and playing an important role in the immune cells. It is mainly manifested in the hyperkeratosis of the palms of the hands (a) and soles of the feet (b). The etiology follows an autosomal recessive pattern of inheritance with a prevalence of four per million live births.   Source: http://pocketdentistry.com/conditions-associated-with-premature-exfoliation-of-primary-teeth-or-delayed-eruption-of-permanent-teeth/

a. Under this condition, the onset that is associated with the dental changes starts with the eruption of the primary teeth, marked by the start of hyperkeratosis. The common manifestation is the loss of teeth as shown in figure (a), and it is related to the severe periodontitis and bone loss. The gingival is hyperemic and edematous, with marked deep periodontal pocketing. As a result, the teeth are more mobile and one experiences discomfort when eating. Dental radiographs reveals and alveolar bone destruction associated with primary dentition as shown in figure (b). b. Source: http://pocketdentistry.com/conditions-associated-with-premature-exfoliation-of-primary-teeth-or-delayed-eruption-of-permanent-teeth/

Chediak- Higashi Syndrome A genetically transmitted condition The melanocytes, platelets and phagocytes are all affected Results in partial albinism, mild bleeding, & recurrent infections The neutrophils have abnormal large lysosomes that can fuse with phagosomes but have impaired ability to release their content which delay killing of microorganism Result in aggressive periodontitis CHS is a genetically transmitted condition. The melanocytes, platelets and phagocytes are all affected which impairs on their functionality. It results in partial albinism, mild bleeding, and recurrent infections. Beginning as infants, children with CHS suffer from recurrent infections, most commonly involving the skin and respiratory systems. Typical processes including periorbital cellulitis, otitis media, pneumonia, pyoderma, abscesses, sinus infections, and dental caries. The neutrophils have abnormal large lysosomes that can fuse with phagosomes but have impaired ability to release their content which delay killing of microorganism. The condition result in aggressive periodontitis Source: Razende M. et al. (2013)

Loss of interdental papillae and heavy accumulation of dental plaque. Misplaced Teeth Generalized swelling of gingival margins These are clinical images showing misplaced teeth, generalized swelling of gingival margins, loss of interdental papillae and heavy accumulation of dental plaque. The alteration of the periodontal tissues may be a primary consequence of such systemic alterations or a secondary effect, causing periodontal disease to progress without any apparent underlying cause, or alternatively maintaining or incrementing the severity of a previously established local condition. The periodontal condition in CHS manifests as early onset periodontitis with premature exfoliation of both dentitions. Source: Razende M. et al. (2013)

Cohen Syndrome A gene mutation in chromose 8 at locus 8q22 gene COH1. Manifested as obesity, mental retardation, craniofacial dysmorphism, and others An autosomal recessive transimssion with variable expression This syndrome is believed to be a gene mutation in chromosome 8 at locus 8q22 gene COH1.Cohen syndrome has several characteristics such as obesity, mental retardation and craniofacial dimorphism. It has an autosomal recessive transmission with variable expression Source: Seow, Bartold, Thong & Taylor (1998)

These images shows the manifestation of Cohen syndrome periodontitis These images shows the manifestation of Cohen syndrome periodontitis. The first image shows the dentition of a female sibling with severe gingival inflammation that is as a result of gross deposits of plaque and calculus. There is evidence of enamel hyper-mineralization. The next shows the dentation of a male sibling with severe gingival inflammation and loss of attachment in the mandibular anterior teeth. Source: Seow, Bartold, Thong & Taylor (1998)

Glycogen Storage Disease Type 1b An inherited autosomal recessive disease Prevalence – 1:150,000 births Caused by hypoglycemia or hepatomegaly Either due to glucose- 6-phosphate deficiency or lack of transporter protein Glycogen storage disease Type 1b is an inherited autosomal recessive disease, which is caused by hypoglycemia or hepatomegaly. It has a prevalence of1:150,000 births. It is either due to glucose-6-phosphate deficiency or lack of transporter protein. Source: Salapata et al. (2006)

a. Localized early onset gingivitis b. Generalized severe periodontitis The main feature of the glycogen storage disease type 1 as manifested in periodontitis is the early onset of gingivitis that soon leas to severe periodontal disease as shown in figure a and b. The pathway is mediated by neutropenia which lowers the ability of the body to fight bacteria. There are present oral mucosal lessons that are discrete, deep, , irregular, recurrent, and are usually covered by whitish pseudo membrane. There are recurrent incidences of oral infection and vaulted palate. Source: Laskaris and Scully (2003)

Ehlers-Danlos syndrome (EDS) Ehlers-Danlos syndrome (EDS) is a hereditary collagen disease manifested as dermatological and joint disorders. Occurs in 8 forms: Type V – Associated with X chromosome Type VII - Characterized by generalized early-onset periodontitis Ehlers-Danlos syndrome (EDS) is a hereditary collagen disease manifested as dermatological and joint disorders. It mainly occurs in 8 forms: Type V – Associated with X chromosome, and mostly carried by women. Type VII - Characterized by generalized early-onset periodontitis Source: Rahman et al. (2003).

Missing teeth restored Bacteria biofilm Missing teeth restored In type VIII, the possibility of gingivitis and periodontitis is increased as shown in the images. The two main pathways include plaque accumulation and dental anomalies. The risk of plaque accumulation is increased by thing oral mucosa. Individuals with this condition have a thing oral mucosa, which means it easily tear and exposes the teeth roots to bacterial infections. In addition, individuals are also likely to lack labial or lingua frenula that leads to a spectrum of dental anomalies. A spectrum of dental anomalies have been described, particularly in classical and hypermobile including high cusps and deep fissures of premolars and molars, shortened or abnormally shaped roots with stones in the pulp of crowns, and enamel hypoplasia (underdevelopment) with microscopic evidence of various enamel and/or dentine defects. There is a high possibility of enamel defects that predispose teeth to loss of crowns increasing the risk of carries. Severe gingival recession Source: Rahman et al. (2003).

Conclusion Periodontitis may be caused by associated systemic diseases Most of these disease occurs as a result of genetic disorders Arising case of periodontitis should be appropriately managed because these conditions are irreversible. In conclusion, periodontitis may be caused by the systemic diseases as discussed in this presentation. We have only discussed eight diseases but there are many others. Most of these condition occurs as a result of genetic disorders, which means they are not curable. Therefore, the arising case of periodontitis should be appropriately managed because these conditions are irreversible.

References Khocht, A. (2011). Genetics and etiology of Down Syndrome. Subrata Dey publishers. Pocket dentistry. Retrieved from http://pocketdentistry.com/conditions- associated-with-premature-exfoliation-of-primary-teeth-or-delayed-eruption-of- permanent-teeth/b Garcia, M. B. et al. (2011). Type I leucocyte adhesion deficiency (LAD I). Report of a case. doi: 10.1016/j.aller.2011.05.013 Razende M. et al. (2013). Chediak-Higashi Syndrome and Premature Exfoliation of Primary Teeth. Braz. Dent. 24(6) doi.org/10.1590/0103- 6440201302258 Seow, K., Bartold, P., Thong, H., & Taylor, K. (1998). Cohen syndrome with neutropenia-induced periodontitis managed with granulocyte colony- stimulating factor (G-CSF): A case report. Pediatric Dentistry, 20(5), 350-354 Salapata, Y. et al. (2006). Oral manifestations in glycogen storage disease type 1b. Journal of Pathology & Medicine, 24(3), 136-139 Laskaris, G. & Scully, C. (2003). Periodontal Manifestations of Local and Systemic Diseases: Color Atlas and Text. Springer. Rahman, N. et al. (2003). Ehlers-Danlos Syndrome with Severe Early-Onset Periodontal Disease (EDS-VIII) Is a Distinct, Heterogeneous Disorder with One Predisposition Gene at Chromosome 12p13. American Journal of Human Genetics, 73(1), 198-204 Here are the references: Khocht, A. (2011). Genetics and etiology of Down Syndrome. Subrata Dey publishers. Pocket dentistry. Retrieved from http://pocketdentistry.com/conditions-associated-with-premature-exfoliation-of-primary-teeth-or-delayed-eruption-of-permanent-teeth/b Garcia, M. B. et al. (2011). Type I leucocyte adhesion deficiency (LAD I). Report of a case. doi: 10.1016/j.aller.2011.05.013 Razende M. et al. (2013). Chediak-Higashi Syndrome and Premature Exfoliation of Primary Teeth. Braz. Dent. 24(6) doi.org/10.1590/0103-6440201302258 Seow, K., Bartold, P., Thong, H., & Taylor, K. (1998). Cohen syndrome with neutropenia-induced periodontitis managed with granulocyte colony-stimulating factor (G-CSF): A case report. Pediatric Dentistry, 20(5), 350-354 Salapata, Y. et al. (2006). Oral manifestations in glycogen storage disease type 1b. Journal of Pathology & Medicine, 24(3), 136-139 Laskaris, G. & Scully, C. (2003). Periodontal Manifestations of Local and Systemic Diseases: Color Atlas and Text. Springer. Rahman, N. et al. (2003). Ehlers-Danlos Syndrome with Severe Early-Onset Periodontal Disease (EDS-VIII) Is a Distinct, Heterogeneous Disorder with One Predisposition Gene at Chromosome 12p13. American Journal of Human Genetics, 73(1), 198-204