Discuss+genetic+factors+associated+with+periodontal+disease.

=Genetic Factors Associated with Periodontal Disease =

Periodontitis as a manifestation of systemic disease:
 * Classification of Periodontitis according to the AAP format regarding Genetic Factors associated with Periodontal Disease**

// 1. Acquired neutropenia // // 2. Leukemias // // 3. Other //
 * A. Associated with hematologic disorders**

1. Familial and cyclic neutropenia: an autosomal dominant genetic blood dyscrasia in which there are periodic reductions in neutrophil count in the blood and bone marrow. Characterized by a cyclic decrease in the number of circulating neutrophils. The episodes last for 2-3 days and during this period of neutropenia, the patient has severe ulcerative, painful gingivitis that can quickly lead to severe periodontal disease with loss of alveolar bone, tooth mobility, tooth exfoliation and crater-like ulcerations on tongue and throughout oral cavity.
 * B. Associated with genetic disorders**


 * 2. Down Syndrome:** ** also known as ** Trisomy 21 is a gross chromosomal abnormality with 47 chromosomes rather than 46 chromosomes. Patients with this condition may present with fissured tongue, decreased saliva, premature tooth loss, hypodontia, abnormally shaped teeth, malocclusion, enamel dysplasia, attrition and periodontal disease. It is also common for these individuals to have macroglossia, and class III malocclusion.


 * 3. Leukocyte adhesion deficiency syndromes**: a autosomal recessive inherited syndrome causes by deficiency of glycoprotein, an adhesive molecule on the surface of WBC that prevent WBC to adhese to blood vessels wall. As a result, WBC cannot leakage from intravenous to extravenoous to the injured side. This syndrome affects mainly infants and as disease progress, it is harder to control and eventually patient will die.


 * 4. Papillon-Lefevre syndrome (PLS):** an autosomal recessive inherited syndrome that is characterized by a decrease in peripheral blood neutrophils, palmoplantar hyperkeratosis, and aggressive periodontitis. This disorder can affect both the primary as well as the permanent dentition. At about 2 yrs old, a marked gingivoperiodontal inflammatory process develops marked by exfoliation of all teeth and then the gingiva returns to normal. Patient has red, scaly keratosis on their palms of their hands and soles of their feet (palmoplantar hyperkeratosis). At 8 or 9 yrs old, the gingivoperiodontal destruction is repeated and ALL permanent teeth are lost before age 14. After the last tooth is lost, the gingiva returns to normal. In some patients with PLS the virulent microorganism //Actinobacillus actinomycetemcomitans// is associated with the aggressive perio disease. The periodontal destruction of this microorganism can be arrested by its elimination, suggesting that aggressive periodontitis is a consequence of a bacterial infection in an immunocompromised host rather then a direct result of the gene mutation


 * 5. Chediak-Higashi syndrome:** an autosomal recessive disorder that affects multiple systems of the body. Patients with this disease exhibit hypopigmentation of the skin, eyes, and hair; prolonged bleeding times; easy bruisability; recurrent infections; abnormal natural killer cell function; and peripheral neuropathy. Affects neutrophil production, chemotaxis, and production. Neutrophil granules fuse and form giant granules making the neutrophil not able to release its contents to fight infections. Oral Characteristics: Aggressive periodontitis with oral ulcerations.


 * 6. Histiocytosis syndromes:** characterized by skin lesions including papules, plaques, vesicles, and hemorrhagic nodules, all of which may manifest in a pattern similar to that of seborrheic dermatitis. Oral symptoms include large ulcerations, ecchymoses, gingivitis, periodontitis, and subsequent tooth loss.


 * 7. Glycogen storage disease**: oral ulcers are common due to severe neutropenia and impaired neutrophil migration.


 * 8. Infantile genetic agranulocytosis:** also known as congenital neutropenia. Common symptoms are abscesses located on various parts of the body including the ear, cutis, lungs and oral cavity.Oral manifestations include Severe tooth loss of the deciduous and permanent dentition that progresses rapidly. The patient needs excellent oral hygiene including antibiotics (Clindamicine).


 * 9. Cohen syndrome:** Is an inherited disorder affecting many parts of the body. Oral manifestations include: micrognathis, microcephaly, short philtrum, high nasal bridge, malar and upper maxillary arches, hypoplasia, prominent central incisors, high vaulted palate, open mouth, small tongue,and hypertrophic gums. Physical characteristics include: decelopmental delay, mental retardation, small head (microcephaly), degenaration of the light sensitive tissue at the back of the eye (retinal dystrophy), joint hypermobility,thick hair, thick eyebrows, long eyelashes, down slanting eyes, bulbuous nasal tip, smooth or shortened area between the nose and the upper lip.
 * 10. Ehlers-Danlos syndrome:** Is a connective tissue disorder with d ental clinical characteristics that include: aggressive periodontitis, severe periodontal bone loss with early loss of deciduous and permanent teeth, premature dental inflammation and gingival recession detected in childhood. Physical features asociated with the disease include articular hypermobility, skin hyperextensibility, tissue fragility, easily scarring, slightly increased tendency to bruising on mild trauma.


 * 11. Hypophosphatasia:** A rare inherited metabolic disorder characterized by a mutation of the alkaline phosphate gene in the tissues. These mutations cause a deficiency in the alkaline phosphates resulting in abnormal mineralization in bone, skeletal anomalies, as well as cementum hypoplasia. Both autosomal recessive and autosomal dominant variants of the disease exist. The disease comes in one of five forms: perinatal, infantile, childhood, adult, and odontohypophosphatasia. Signs and symptoms include bone malformations and higher chance of bone fracture. Both the adult form and odontohypophosphatasial form are marked by premature tooth loss. Early loss of primary teeth is one of the first signs of the condition in children. Affected adults may lose their teeth prematurely and are at increased risk for joint pain and inflammation.


 * 12.** **Gingival Fibromatosis:** An ** a **utosomal dominant disorder. Gingival hypertrophy develops early in life, the teeth will completely be covered with gingiva tissue. The gingiva is very pale and firm with granular corrugated surface and could cause the lips to protrude. Surgery is an option but not recommended till puberty when the growth is slower.


 * 13. Chondroectodermal Dysplasia:** Has an ** a **utosomal recessive inheritance pattern. The patient is a dwarf with shortening of their extremities and polydactyl fingers. The oral manifestations include fusion of the anterior portion of the maxillary gingiva to the upper lip from canine to canine- a V-notch appearance in midline of upper lip. Central incisor are usually lacking and teeth are conical and have enamel hypoplasia.


 * 14. Cleidocranial Dysplasia:** Has an autosomal dominant inheritance pattern. The patient has hypoplasia of their clavicles. The oral manifestations include supernumerary teeth and multiple cysts can develop due to the impacted teeth. The patient may also have possible cleft lip or cleft palate.


 * 15.** **Gardner** **syndrome:** An autosomal dominant disorder. Patients may have osteomas in the frontal bone, mandible, maxilla, and in long bones that can expand bone. Multiple odontomas can occur in the mandible. Teeth may fail to erupt "hypercementosis". Patients could also develop malignant intestinal polyps by 30 years old.


 * 16. Mandibulofacial Dysostosis:** An autosomal dominant disorder. The patient can present with a hypoplastic nose, abnormal or misplaced ears, deafness and an abnormal zygomatic process. The oral manifestations include a "fish-like" mouth with downward sloping lip commissures, teeth that are malposed, malocclusion with an open bite and a predisposition for gingival diseases.


 * 17.Nevoid Basal Cell Carcinoma:** An autosomal dominant disorder. The patient may presents with a basal cell carcinomas on the nose, eyelids, cheeks, neck and arms and can have skeletal anomalies. The oral manifestations of the disease include multiple jaw cysts consisting of odontogenic keratocysts and ameloblastomas. Cysts may develop as early as 5-6 yrs old and can cause an interference with development.


 * 18. Cherubism:** Is an autosomal dominant disorder. The disease is characterised by bilateral facial swelling that appears betwee 1.5 to 4 years of age, it can affect the mandible and maxilla and eyes can become displaced. The facial deformity remains for life, the jaw size will increase in size till puberty and will become stable by age 20-30 years then the bone appears normal. In radiographs the bone will have a soap bubble multilocular appearance. The radiolucent areas are filled with fibrous CT that contain multinucleated giant cells. The disease may cause problems with tooth eruption and/or development.


 * 19. Osteogenesis Imperfecta:** Is 30% autosomal dominant and 70% autosomal recessive. It consists of a basic defect in the collagen and results in bones that fracture easily. The oral manifestations include dentinogenesis imperfecta of the primary teeth, and smaller than normal teeth. Enamel is lost from the abnormal dentin that is not able to support it.


 * 20. Cleft Palate/Lip:** Is an autosomal dominant birth defect or can be of unknown etiology. Cleft lip is more common in males and cleft palate is more common in females. Patients generally have surgery between 15-18 months to correct the disorder, however malocclusion and scarring are common side effects.


 * 21. Hereditary Hemorrhagic Telangiectasia:** Is an autosomal dominant disorder. A telangiectasia is a purplish red/slightly red papule or permanently enlarged capillary. Physically this disorder appears as multiple capillary dilations of the skin and mucous membranes. The skin of the face may have numerous pinpoint and spider-like telangiectases. The lips, eyelids, nose, scalp, ears and nasal mucosa may be affected. This may result in numerous nose bleeds. In the oral cavity Telangiectases may appear on the tip and anterior dorsum of the tongue, palate, gingiva, and buccal mucosa; may hemorrhage from lips and tongue. What we as clinicians need to be concerned with is gingival hemorrhage. We can help to control these by pressure packs.

Medullary carcinoma of the thyroid develops in 2nd decade of life, metastatic lesions may develop and the carcinomas can be found by evaluating plasma levels of calcitonin (thyroid hormone). Pheochromocytoma develops in the 2nd or 3rd decade of life, bilateral benign neoplasm usually develop in the ganglia around the adrenal glands. Symptoms include: night sweats, HBP, episodes of severe diarrhea, cutaneous pigmentation, and skeletal abnormalities.
 * 22. Multiple Mucosal Neuroma Syndrome:** Is an autosomal dominant disorder. You may also see this disorder being called: Multiple endocrine neoplasia, type 2B (MEN2B). This is a combination syndrome because many things can occur at the same time. Those multipul symptom include: multiple mucosal neuromas, medullary carcinoma of the thyroid gland, and pheochromocytoma. Oral neuromas may be the first visible manifestation of this syndrome. Early diagnosis is imperative due to high malignant potential of the thyroid physicians may preventatively remove thyroid. Physically, we will see: tall, thick, large lips and often everted upper eyelids; neuromas can occur on the eyelids. Oral manifestations (include a combination of 3 conditions): Mucosal neuromas are prominent on the lips and the anterior dorsal surface of the tongue (can occur in the first few years of life); mucosal neuromas can also occur on buccal mucosa and are characterized by multiple, mobile, firm lumps covered by normal mucosa that are aggregates of nerve tissue.


 * 23. Neurofibromatosis of von Recklinghausen:** Is an autosomal dominant disorder that is characterized by multiple neurofibromas that appear as papules and growths that vary in size on facial skin (eyelids). They can arise at birth or early in life and are present anywhere and may turn malignant. 10% of these patients have oral manifestations of the disease which include one or multiple tumors at any location in the oral mucosa- usually the lateral borders of the tongue. 90% of patients will have cafe au lait pigmentation which usually precedes the neurofibromas.


 * 24. Peutz-Jeghers Syndrome:** Is an autosomal dominant syndrome that is characterized by multiple melanotic macular pigmentation of the skin and mucosa (eyes, nose, mouth) and gastrointestinal polyposis which rarely turn malignant.


 * 25. White Sponge Nevus:** Described by Cannon in 1935 and is also is known as familial white folded mucosal dysplasia, leukoderma exfoliativum mucosae oris, and hereditary leukokeratosis. It is a benign, uncommon, autosomal dominant disorder that involves a mutation in mucosal keratin that predominantly affects non-keratinized stratified-squamous epithelia. Cases without a familial background have been reported. The onset is in early childhood, with 50 percent of patients being diagnosed before age 20. White sponge nevus is attributed to a mutation in the helical domain of mucosal specific keratins, K4 and K13. The mutations are in the form of insertions, deletions, and substitutions that result in abnormal aggregation of tonofilaments and keratin filaments instability. Lesions appear as white-to-gray, diffuse, painless, spongy folded plaques that are typically found on the buccal mucosa. White sponge nevus may be confused with other white lesions of the oral mucosa, which include cheek biting, lichen planus, lupus erythematosus, hereditary benign intraepithelial dyskeratosis, tobacco-induced keratotic lesions, pachyonychia congenita, keratosis follicularis, and candidiasis.

There are several inherited and or genetic disorders were early and aggressive periodontitis are consistent features.
 * Aggressive Periodontitis and its Associations with Genetic Disorders:**


 * 1.** **Hypophosphatasia: See #11 above**


 * 2.** **Papillon-Lefevre Syndrome (PLS): See #4 above**