This document discusses various syndromes that can affect the periodontium. It begins by defining systemic conditions and syndromes. It then classifies syndromes affecting the periodontium into 10 categories based on their effects such as causing white lesions, red lesions, ulcers/erosions, pigmentation, lumps/swellings, bleeding, periodontal destruction, defects in the gingivolabial fold, and effects on the periodontal ligament. Several specific syndromes are discussed in detail for each category.

1. SYNDROMES AFFECTING
THE PERIODONTIUM

2. Introduction
• Systemic conditions are defined as the
naturally occurring or induced states that are
expected to exert general effects throughout
the body.
• They can be hormonal, nutritional, genetic or
related to age or comprise drug intake or
habits such as smoking.

3. • Systemic disorders are true abnormalities or
diseases having signs and symptoms that
deviate from normal and that define diseases,
such as diabetes mellitus.
• It is well known that systemic conditions can
manifest in the oral cavity.

4. Definition of a syndrome:
“A syndrome is a combination of symptoms
resulting from a single cause or so commonly
occurring as to constitute a distinct clinical
entity. “
( Dorland’s medical dictionary)

5. Definition of a syndrome:
“A group of symptoms that together are
characteristic of a specific disorder, disease, or
the like “
( dictionary.com )

6. CLASSIFICATION OF SYNDROMES
AFFECTING THE PERIODONTIUM

7. Classification
1. Syndromes causing white lesions in the
gingiva- Focal palmoplantar and oral mucosa
hyperkeratosis syndrome
2. Syndromes causing red lesions in the gingiva-
Melkersson –Rosenthal syndrome, Sturge-
Webber syndrome, Klippel-Trenaunay-Weber
syndrome, Sjogren’s syndrome, Osler-Rendu-
Weber syndrome

8. Classification
3. Syndromes causing ulcers and erosions in the
gingiva- Bechet’s syndrome, Reiter’s
syndrome, Myelodysplastic Syndrome
4. Syndromes causing pigmentation in the
gingiva- Peutz-Jegher’s syndrome, Albright’s
syndrome

9. Classification
5. Syndromes causing localized lumps or swellings in the
gingiva- Gardener’s syndrome, Turner’s syndrome
6. Syndromes causing generalized lumps or swellings in the
gingiva- Laband’s syndrome, Hurler’s syndrome, Sturge-
Webber syndrome, Klippel-Trenaunay-Weber syndrome,
Rutherford syndrome, Cowden’s syndrome, Goltz-Gorlin
syndrome, Murray-Puretic-Dreshcer syndrome, Cross
syndrome, Ramon syndrome, Bourneville-Pringle syndrome

10. Classification
7. Syndromes causing gingival bleeding- Sturge-Webber syndrome,
Klippel-Trenaunay-Weber syndrome, Chediak-Higashi syndrome,
Osler-Rendu-Weber syndrome
8. Syndromes causing periodontal destruction- Chediak-Higashi
syndrome, Hyperimmunoglobulin E syndrome, Congenital
neutropenia (Kostmann syndrome), Felty’s syndrome, Lazy
leukocyte syndrome, Leukocyte adhesion deficiency syndrome,
Ehlers–Danlos syndrome, Hypotrichosis osteolysis periodontitis
palmoplantar keratoderma syndrome, Kindler syndrome

11. 9. Syndromes causing defects in the
gingivolabial fold- Orofaciodigital syndrome
type I, Ellis van Crevald syndrome
10. syndromes affecting the periodontal
ligament : CREST syndrome, Thibierge-
Wissenbach syndrome

12. SYNDROMES CAUSING WHITE LESIONS
IN THE GINGIVA

13. 1. Focal palmoplantar and oral mucosa
hyperkeratosis syndrome -OMIM 148730
Definition:
• also called as hyperkeratosis or attached
gingival hyperkeratosis.
• It is unusual genetic disorder characterized by
oral mucosal and dermal hyperkeratosis
Etiology: Genetic. Inherited as an autosomal
dominant trait.

14. Clinical features:
• marked white
hyperkeratosis of the
attached gingival,
presenting clinically as
leukoplakia
• There is no inflammation
or attachment loss.

15. • White hyperkeratotic lesions at the
weight bearing and pressure
related areas of the palms and
soles are always present.
• Nail dystrophy and hyperhidrosis
may also occur.
• The hyperkeratosis develops early
in childhood and the severity
increases with age.

16. Differential diagnosis:
• Leukoplakia
• white sponge nevus
• pachyonychia congenita
• dyskeratosis congenita
Diagnosis: the diagnosis is mainly based on clinical criteria.
Biopsy and histological examination are also used.
Treatment: local and systemic aromatic retinoids with partial
success.

17. SYNDROMES CAUSING RED LESIONS
IN THE GINGIVA

18. 1. Klippel-Trenauny-Weber syndrome-
OMIM 14900
• Definition: is an uncommon
dysplastic vascular disorder.
• Etiology: dysplatic
malformation
Haemangiomas on the
leg

19. Clinical features:
• the gingival lesions appear
as capillary or cavernous
haemangiomas occasionally
leading to gingival
overgrowth that may cover
the crown of the teeth.
• Premature tooth eruption
and alveolar bone
overgrowth may occur.
• The oral mucosa
lesions are also
haemangiomas,
particularly on the hard
and soft palate.

20. • Multiple facial haemangiomas, ocular disorders (scleral
pigmentation, glaucoma, cataract, iris heterochromia), vascular
masses that involve soft tissue and bone leading to assymetrical
enlargement of the extremities, haemangiomas in the internal
organs are common.

21. Diagnosis: the diagnosis is based on clinical
criteria
Differential diagnosis:
• isolated haemangiomas
• Sturge Webber syndrome
• Maffuci’s syndrome.
Treatment: palliative, Laser may improve skin
lesions

22. 2. Sturge-Webber syndrome- OMIM 176920
(Encephalotrigeminal angiomatosis)
• Definition: is a rare sporadic congenital
hamartomatous vascular disorder typically
involving areas innervated by the trigeminal
nerve.
• Etiology: obscure, developmental anomaly.

23. Clinical features:
• typically unilateral
haemangiomas, usually
capillary, on the attached
gingival and alveolar
mucosa may be seen
occasionally leading to
gingival hyperplasia and
premature or rarely
delayed eruption.

24. • The lesions have a bright red or purple colour
and are usually flat.
• Dentists must be careful during tooth
extractions and periodontal surgery so as to
avoid bleeding complications.

25. • Unilateral oral haemangiomas may be found on the buccal
mucosa, tongue and lips.
• Unilateral facial haemagioma is the most characteristic and
consistent feature, it is evident at birth and characteristically it
is confined to the area supplied by the trigeminal nerve.
• Haemangiomas of the leptomeninges, brain calcification,
epilepsy, ocular disorders may also be present.

26. Diagnosis:
• Based on clinical examination.
• CT scan,
• Histopathological examinations.
Differential diagnosis:
• solitary haemangioma
• Klippel-Trenauny-Weber syndrome.
Treatment: laser therapy

27. 3. Melkersson –Rosenthal syndrome-
OMIM- 15590
Definition:
• is a rare disorder.
• It consists of the triad of recurrent facial
swelling, facial paralysis and fissured tongue.
Etiology: unknown

28. Clinical features:
• gingival lesions are present as
irreregular, oedematous
swelling, slightly
erythematous, affecting
mainly the anterior
interdental papillae and free
and attached gingiva.
• Granulomatous cheilitis
presenting as diffuse
recurrent swelling of the lips
is the cardinal feature of the
syndrome.

29. • Swelling of the lips is usually the first
sign.
• After a long period of attacks, the
swelling persists and can become
permanent.
• Buccal, palatal and lingual swellings
may also occur.
• Facial palsy and fissured tongue
accompany the other lesions.

30. Diagnosis:
• Based on clinical examination.
• Allergy tests
• biopsy and Histopathological examinations.
Differential diagnosis:
• angioedema
• cheilitis glandularis
• Crohn’s disease
• Sarcoidosis
• Amyloidosis
Treatment: dental plaque control and surgical excision of the gingival lesions.
Corticosteroid (topical or systemic) administration. Neurological
consultation.

31. 4. Sjogren’s syndrome- OMIM 270510
• Definition: is a relatively common, chronic
autoimmune disorder.
• Etiology: obscure; viral infection, genetic
factors and autoimmunity have been implied.

32. Clinical features:
• chronic gingivitis, (localized or
generalized) due to xerostomia
and/or candida infection may
occur.
• Rarely, alveolar bone loss can
also be seen.
• The oral mucosa is reddish, dry,
smooth and shiny.

33. • Oral soreness, discomfort and dysphagia are
seen.
• Candidiasis, angular cheilitis and dental caries
are relatively common.
• Recurrent swellings of the parotid and other
salivary glands can occur.

34. Diagnosis:
• clinical diagnosis should be confirmed by laboratory tests.
• Biopsy and Histopathological examinations of the salivary glands
• Serological tests- Antinuclear antibodies, Anti-SSA (Ro) , Anti-SSB antibodies,
Rheumatoid factor
Differential diagnosis:
• GVHD
• Xerostomia due to drugs
• Systemic sclerosis
• Mixed connective tissue disease
Treatment: good dental plaque control. Saliva and tears substitute. Antimalarial
drugs, corticosteroids, immunosuppresants

35. 5. Osler-Rendu-Weber syndrome/ hereditary
haemmorhagic telangiectasia- OMIM 187300
• Definition: is a rare disorder characterized by
permanent small dilation of vessels.
• Etiology: genetic. Inherited as an autosomal
trait.

36. Clinical features:
• the gingival lesions appear as small, localized or multiple, bright red
macules that characteristically disappear when pressure is applied.
• Gingival recurrent bleeding, usually, during or after tooth brushing,
is frequent.
• The oral mucosal manifestations are characterized by multiple
telangiectasias and rarely bleeding.
• Persistent recurrent nose bleeding is usually the first and common
clinical sign of the disease. Multiple telangiectasias of the
gastrointestinal tract and skin are common.

37. Diagnosis:
• Based on clinical examination.
• Histopathological examinations.
Differential diagnosis:
• CREST syndrome
• Fabry’s disease
• Maffuci’s syndrome
Treatment: not usually required. Laser therapy is suggested for
lesions that bleed repeatedly.

38. SYNDROMES CAUSING DEFECTS
IN THE GINGIVOLABIAL FOLD

39. 1. Orofaciodigital syndrome type I-OMIM
311200
• Definition: is an uncommon disorder in the
group of orofaciodigital syndromes
• Etiology: genetic. It is inherited as an X linked
dominant trait

40. Clinical features:
• the gingival involvement
characterized by multiple
hyperplastic fibrous bands
traversing the gingivolabial and
gingivobuccal fold, hypertrophy
and shortening of the frenulum
of the lips and the tongue.
• These may result in hyperplastic
gingivitis and gingival recession.

41. • The oral mucosal lesions include multilobed or bifid tongue,
with multiple hamartoma, lips and palate clefts,
supernumerary teeth, teeth malposition and missing teeth,
hypoplastic mandible.
• Frontal bossing, ocular hypertelorism, short upper lip, broad
nasal root, asymmetry of the nostrils, polydactyly,
brachydactyly, clinodactyly and syndactyly are common.
• The skin manifestations are xerostomia, milia, alopecia and
sparse hair.
• Learning disability and polycystic kidneys may occasionally
occur.

42. Diagnosis: the diagnosis is based clinical criteria.
Differential diagnosis: orofaciodigital syndrome
type II, chondroectodermal dysplasia,
oculodigital syndrome.
Treatment: surgical reconstruction of oral
frenulum, gingivolabial and gingivobuccal
folds. Symptomatic for the rest of the lesions.

43. 2. Ellis van Crevald syndrome- OMIM
225500
• Also called chondroectodermal dysplasia
• It is an autosomal recessive disorder.

44. Clinical features
• There is fusion of the middle portion of the
upper lip to the gingiva leading to the
disappearance of the mucolabial fold and
multiple frenula are the most characteristic
oral manifestation. Oligodontia and small
clinical crowns may be seen.
• Chondrodysplasia of the long bones,
bilateral polydactyly, shortened extremities,
thin and sparse hair, dystrophic nails, heart
defects and genital abnormalities are
common.

45. SYNDROMES CAUSING ULCERS AND
EROSIONS IN THE GINGIVA

46. 1. Bechet’s syndrome- OMIM 109650
• Definition: is a chronic multisystemic disorder
that affects more commonly certain ethnic
groups ( Japanese, Turkish, Greek and other
Mediterranean groups)
• Etiology: obscure.

47. Clinical features:
• the main feature is recurrent
apthous ulceration ( minor,
major, herpetiform,
atypical).
• Painful ulcers can develop
on the attached gingiva.

48. • Conjunctivitis, iritis, iridocyclitis with
hypopyon, uveitis are the frequent eye
manifestation.
• The skin lesions present as round genital
ulcers.
• Folluculitis, erythema, papules and necrosis
are common cutaneous lesions.

49. Diagnosis:
• Based on clinical examination.
• Histopathological examinations.
Differential diagnosis:
• Apthous ulcers
• Pemphigous
• Pemphigoid
• Erythema multiformae
• Necrotizing ulcerative gingivitis
• Neutropenia
• Leukaemia
• Langerhans cell histiocytosis
Treatment: corticosteroid – topical and systemic

50. 2. Reiter’s syndrome
• Definition: is an uncommon chronic
multisystemic disorder that may be triggered
by an infectious agent in a genetically
susceptible individual.
• Etiology: the exact mechanism remains
unknown. Immunological mechanisms have
been implicated.

51. Clinical features:
• the gingival lesions appear as
localized or generalized non
specific erythema, usually on the
attached gingiva, occasionally
associated with superficial, slightly
sensitive erosions.
• The mucosal lesions are
characterized by diffuse
erythematous areas intermixed
with thin whitish dots or lines, and
superficial erosions.

52.  Localized loss of the tongue filiform papillae in
the form of geographic tongue can occur.
• The skin manifestations appear as
macular, vesicular or pustular,
psoriasiform lesions and
keratoderma. Other
manifestations include
conjunctivitis, cyclic balanitis, non
gonococcal urethrits, prostatitis,
cervicitis and nail disturbances.
• The most characteristic feature is
the symmetrical arthritis of 6-7
joints.

53. Diagnosis:
• Based on clinical examination.
• Histopathological examinations.
• Blood and serological tests, HLA antigens
• Synovial fluid analysis.
Differential diagnosis:
• Erythema multiformae
• Bechet’s syndrome
• Geographic stomatitis
• Drug eruption
Treatment: corticosteroid – topical and systemic. NSAIDs

54. 3. Myelodysplastic Syndrome
• Definition: forms a heterogeneous group of
refractory anaemias often associated with
thrombocytopenia, neutropenia and/or
monocytosis.
• Etiology: unknown. Can develop secondarily to
radiotherapy or chemotherapy.

55. Clinical features:
• the gingival lesions may
appear as chronic, localized
swellings and/or
ulcerations, associated with
bleeding.
• The oral lesions appear as
persistent and recurrent
painful ulcerations and
bleedings.

56. • Less often candidiasis may develop.
• Multiple bacterial infections and
haemmorhages are the main features of the
disease due to neutropenia and
thrombocytopenia.
• Malaise, fatigue, fever are common
symptoms.

57. Diagnosis:
• Clinical diagnosis should be confirmed by laboratory tests.
• Complete blood count and bone marrow aspiration and biopsy
Differential diagnosis:
• Leukemias
• Agranulocytosis
• Neutropenia
• Aplastic anaemia
• Thrombocytopenia
• Non Hodgkins lymphoma
• Multiple myeloma
• Langherhans cell histiocytosis
Treatment: good oral hygiene. Topical oral antiseptics. Systemic
treatment must be left to the hematologist.

58. 4. PFAPA syndrome/Marshall
syndrome
• Stands for- Periodic Fever, Aphthous
stomatitis, Pharyngitis and Adenopathy.
• Oral manifestations - aphthous ulceration on
the oral mucosal tissues. Gingival involvement
is uncommon.

59. SYNDROMES CAUSING PIGMENTATION
IN THE GINGIVA

60. 1. Peutz-Jegher’s syndrome-OMIM
175200
Consists of
• Familial generalized intestinal polyposis
• Pigmented spots on the face, oral cavity and
sometimes, hands and feet

61. 2. Albright’s syndrome- OMIM 174800
Consists of –
• Polyostotic fibrous dysplasia
• Pigmented lesions of the skin and mucous
membrane
• Endocrine disturbances- precocious puberty

62. SYNDROMES CAUSING LOCALIZED LUMPS
OR SWELLINGS IN THE GINGIVA

63. 1. Gardener’s syndrome- OMIM
175100
• Definition: is a rare disorder in the group of
familial colorectal polyposis syndromes.
• Etiology: genetic. It is inherited as an
autosomal dominant trait.

64. Clinical features:
• It is important for dentists to diagnose the oral
lesions of the syndrome as early as possible and
to refer the patient to a gastroenterologist.
• Central osteomas in other sites of the jaws,
multiple odontomas, multiple impacted
supernumerary teeth and rarely benign oral soft
tissue tumors may occur.

65. • the alveolar bone
lesions are
characterized by
multiple osteomas
that present as
painless, hard masses
covered by normal
attached gingival and
alveolar mucosa.

66. • Multiple osteomas of the skull, paranasal
sinuses and calvaria may develop.
• Gastrointestinal manifestations are common
and appear as multiple polyps of the colon and
rectum that are characterized by a high rate of
malignant transformation into adenocarcinoma.
• Skin lesions are epidermoid cysts, multiple
fibromas and hyperpigmentation.

67. Diagnosis:
• radiographic examination of the jaws, skull and intestinal tract.
• Biopsy and histolopathological examination of tumours and polyps.
Differential diagnosis:
• isolated osteomas and exostoses,
• odontogenic tumours,
• Peutz-Jeghers syndrome,
• Cowden’s syndrome
Treatment: osteomas do not require excision unless they cause
symptoms or cosmetic problems. The intestinal polyps must be
under observation by the specialist.

68. 2.Turner’s syndrome OMIM 313000
Oral manifestations- torus mandibularis- bony lumps, which grow
slowly, appear in adolescence and usually cease growth in late
teens. The lumps are bone had with normal overlying mucosa,
asymptomatic, benign and of no consequence.
Diagnosis: clinical features and radiographic examination
Differential diagnosis; exclude unerupted teeth
Treatment- excision only if it causes difficulty, as in placement of
dentures.

69. SYNDROMES CAUSING GENERALIZED
LUMPS OR SWELLINGS IN THE GINGIVA

70. 1. Laband syndrome- OMIM 135500
• Definition: It is a rare disorder characterized
by a broad spectrum of diseases.
• Etiology: genetic. It is an autosomal dominant
disorder

71. Clinical features:
• consists of gingival
fibromatosis, ear, nose,
bone and nail defects with
splenomegaly.
• Macroglossia and
enlargement of lips are less
common.

72. •Large nose and pinnae,
hypoplastic or absent
thumb nails, rudimentary
or missing terminal
phalanges, pes cavus,
joint hypermobility are
common.
•Hepatomegaly,
splenomegaly and
learning disability have
been noted.

73. Diagnosis: based on clinical criteria
Differential diagnosis:
• hereditary gingival fibromatosis,
• drug influenced gingival enlargement,
• other syndromes associated with gingival enlargement
• alpha mannosidosis.
Treatment: good oral hygiene, gingivectomy

74. 2. Cross syndrome
• It is autosomal dominant disorder manifesting
as gingival fibromatosis, microphthalmia,
mental retardation, atelosis and
hypopigmentation

75. 3. Murray-Puretic- Drescher
syndrome-OMIM 228600
• It is an autosomal recessive disorder
manifesting as gingival fibromatosis, multiple
hyaline fibrous tumors on the scalp and back,
joint changes with osteoporosis of terminal
phalanges

76. 4. Rutherford syndrome
• It is an autosomal dominant disorder with
gingival fibromatosis, mental deficiency,
aggressive behaviour, corneal opacities,
impaired tooth eruption, root resorption and
dentigerous cysts.

77. 5. Hurler’s syndrome-OMIM 2607014
• Definition: It is also called as
Mucopolysaccharidosis I (MPS I). It is a rare
but most common form of
Mucopolysaccharide metabolic disorders.
• Etiology: genetic. Inherited as an autosomal
recessive trait. The basic defect is the
deficiency of the enzyme alpha L iduronidase
resulting in the accumulation and deposition
of heparin sulphate and dermatan sulphate
within the tissues and their excessive

78. Clinical features:
• it becomes apparent in early childhood and the
children usually die before the age of 10 due to
respiratory infection or cardiac disease.
• There is deposition of mucopolysaccharides into
the tissues.

79. •The main feature is gingival overgrowth that may fully
or partially cover the crowns of the teeth, particularly in
the anterior area of the maxilla.
•The overgrowth is mostly the result of microbial dental
plaque, mouth breathing and deposition of dermatan
sulphate and heparan sulphate in the gingival tissue.

80. • Other oral manifestations include macrocheila, macroglossia,
open mouth with protruding tongue, numerous impacted teeth,
large interdental spaces and teeth dislocation.
• Growth retardation, craniofacial malformation, characteristic
facies, scoliosis, stiff joints and chondrodystrophy are common.
• There is corneal scarring and clouding that frequently leads to
blindness, learning disability
• Cardiac failure and lung infections may also occur.

81. Diagnosis: is based on clinical and histochemical evaluation-
• Histochemical evaluation of alpha L iduronidase
• Detection of heparan sulphate and dermatan sulphate in the urine
• Radiographic examination
Differential diagnosis:
• hereditary gingival fibromatosis
• Alpha mannosidosis.
• Mouth breathing gingivitis
• Other forms of mucopolysacharidoses.
Treatment: good oral hygiene, gingivectomy, management of dental problems,
supportive for the other manifestations.

82. 6. Focal Dermal Hypoplasia syndrome/
Goltz- Gorlin syndrome-OMIM 305600
• Definition: is an uncommon disorder
characterized by multiple abnormalities.
• Etiology: genetic. It is inherited as an X linked
dominant trait.

83. Clinical features:
• the gingival lesions are
papillomas.
• Multiple papillomas on the oral
mucosa are present in about
50% of the cases.
• Oligodontia, hypodontia,
enamel dysplasia and
malocclusion, oral clefts are
common.

84. • Skin manifestations
include atrophic linear
lesions, atrophic and
hyperpigmented
plaques, telangectasias
and soft yellowish
nodules.

85. • Sparse hair and dystrophic nails may be seen.
• Syndactyly, brachydactyly, oligodactyly or
polydactyly, clinodactyly extremity asymmetry,
scoliosis and microcephaly may occur.
• Eye anomalies, learning disabilities are less
common findings.

86. Diagnosis: the diagnosis is based on clinical
criteria. Biopsy and histopatholoogical
examination of the skin and oral lesions.
Differential diagnosis:
• multiple oral papillomas
• multiple oral condylomas
• focal epithelial hyperplasia

87. 7. Bourneville-Pringle syndrome-
OMIM 191100
• Definition – tuberous sclerosis of the
Bourneville-Pringle syndrome or epiloia, is an
uncommon disorder characterized by
mucocutaneous angiofibromas, learning
disabilities and seizures.
• Etiology- genetic. It is inherited as an
autosomal dominant trait with variable
expressivity.

88. Clinical features-
• the gingival lesions are the
most characteristics oral lesions
and present as multiple,
painless, fibrous nodules with
smooth surface and normal or
whitish colour.
• The anterior gingiva is more
frequently affected.
• The oral mucosa lesions are
similar to those seen on the
gingiva.

90. • Cleft palate and lip, vaulted palate, macroglossia and enamel
pits may occur.
• The skin lesions are common and present as multiple small,
red to brown nodules (angiofibromas), mainly in the
nasolabial folds and elsewhere in the face.
• Learning disability, seizures and neural hamartomas are
common.
• Cardiac rhabdomyoma, multiple retinal hamartomas, lung and
renal abnormalities may also occur.

91. Diagnosis: Is based on clinical and laboratory criteria.
• Biopsy and histopathological examination of the cutaneous and oral
lesions.
• Brain CT.
• EEG.
Differential diagnosis:
• Cowden’s disease
• neurofibromatosis
• lipoid proteinosis
• acanthosis nigrans
• focal dermal hypoplasia syndrome.
Treatment: symptomatic

92. 8. Ramon Syndrome –OMIM 266270
• First described by Ramon et al. (1967)
• A familial disease characterized by mild
mental retardation, growth retardation,
epilepsy, fibrous dysplasia of the maxillae,
narrow palate, cherubism, hypertrichosis,
juvenile rheumatoid arthritis, and gingival
fibromatosis.
• Inheritance is autosomal recessive.

93. Cowden’s syndrome/multiple
hamartoma syndrome
• Is an uncommon disorder characterized by a
wide spectrum of mucocutaneous lesions
usually associated with breast, thyroid and
other organ disorders
• It is a genetic disorder with an autosomal
dominant trait.

94. • The gingival lesions appear as multiple, small, smooth
pale/whitish painless papules or nodules that may be isolated or
coalesce in a cobblestone pattern on the free or attached gingiva
or the edentulous alveolar mucosa
• Skin lesions appear as multiple papillomatous papules or small
nodules that are hair follicle hamartomas
• Dermal fibromas are also common
• Several breast and thyroid gland tumours are also common

95. SYNDROMES AFFECTING THE
PERIODONTAL LIGAMENT

96. Scleroderma
• Scleroderma (OMIM 181750) is a connective
tissue disorder the characteristic feature of
which is an inflammatory, vascular and fibrotic
change in the skin and other structures.
• Scleroderma is associated with two
syndromes- CREST syndrome, Thibierge-
Wissenbach syndrome

97. CREST
syndrome

98. Thibierge-Wissenbach syndrome
• Describes extensive subcutaneous tissue
calcinosis.

99. The periodontal manifestations of
scleroderma are: ( Stafne, Austin 1944)
• Widening of the periodontal ligament space occurs at the
expense of the alveolar bone
• The periodontal space of the posterior teeth is more likely to be
affected than the anterior teeth. This may be due to the
difference in occlusal loading.
• The increase in width of the periodontal ligament space is
uniform all around the tooth.
• The affected teeth are not in supraocclusion.
• The gingival attachment is unbroken and the gingival crevice is
normal.

100. The histological picture is as
follows-
• Erratic bone resorption in the region of the alveolar bone
approximating the periodontal ligament
• Thickening due to proportionate increase of collagen and oxytalan
fibres which contain areas of degradation
• Sclerosis and hyalinization of collagen, particularly adjacent to the
teeth. There is the development of elastic fibres in this region.
• There is formation of coal areas of bone or irreregular areas
calcified deposits. ( Fulner and White, 1962)

101. Radiographic appearance of
scleroderma

102. Other clinical manifestations
• Higher incidence of periodontal disease in
scleroderma patients than in normal patients (
Mammary et al, 1981)
• Crenations are found on the buccal mucosa and
this could lead to severe mucogingival
problems. ( Eversole et al, 1983)
• Microstomia, limited mouth opening and hand
changes associated with scleroderma can
impede effective mechanical plaque control by
the patient.

104. SYNDROMES
AFFECTING THE
PERIODONTIUM
PART II

105. SYNDROMES CAUSING
PERIODONTAL DESTRUCTION

106. A. Neutrophil defects
• The importance of PMN- the cellular defender, in the
pathogenesis of periodontal disease is dramatically brought to
the forefront in those systemic diseases that are characterized
by either an innate or an induced abnormality in the number
and/or function of the neutrophil and a concomitant
destruction of the periodontium.
• Defects in any of the functions (qualitative defect) or a
marked decrease in the number of neutrophils (quantitative
defect) capable of responding to the site of infection may
result in varying degrees of susceptibility to infection.

107. Neutrophil defects
Quantitative
Qualitative
B M periphery
R & A Phagochemo

108. Quantitative defects
• A relative deficiency in neutrophil number can dramatically
increase susceptibility to infectious diseases.
• Neutropenia is considered clinically significant when the absolute
neutrophil count falls below 1,000 cells/ml (normal adult range:
1,800– 8,000 cells/ml).
• Diagnosis of neutropenia is based on clinical signs and symptoms
as well as absolute neutrophil counts.

109. The pathophysiology of neutropenia may
be -
• abnormalities of bone marrow stem cell development,
• impaired release of neutrophils from the bone marrow,
• abnormalities in distribution of neutrophils between the circulating
and marginating pool in the blood,
• decreased survival of neutrophils in the blood

110. Quantitative defects
At the BM
At the periphery
Kostmann synd Felty’s synd
Lazy leukocyte synd

111. 1. Kostmann syndrome (Congenital
neutropenia) (OMIM 610738;OMIM 605998)
• Congenital neutropenia (Kostmann syndrome) was named after
the Swedish pediatrician who first described the disease in 1950
• Congenital neutropenia is an inherited hematologic disorder
manifesting in the first year of life and characterized by severe
bacterial infections.
• The significant laboratory findings are an absolute neutrophil
count of less than 2,000/ml and an arrest of neutrophil
hematopoiesis at the promyelocyte/ myelocyte stage.

112. Oral manifestations
• gingivitis
• alveolar bone loss
- Carlsson, 2001
• generalized severe periodontitis – Defraaia
2001

113. Other syndromes associated with decreased
neutrophil counts and periodontal destruction
• Hermansky–Pudlak
syndrome
• Shwachman–
Diamond syndrome
• Inherited bone
marrow failure
syndrome

114. 2. Felty’s syndrome
• Felty’s syndrome is an uncommon complication
of rheumatoid arthritis, in which splenomegaly
and leucopenia are the major additional
features.
• Other features are- weight loss, progressive
weakness, hyperpigmentation of the skin,
generalized lymphadenopathy, hepatomegaly,
increased susceptibility to infection, and a
variety of abnormalities in white blood cell
count and function.

115. The leukopenia noted in Felty’s syndrome is primarily
due to a lack of circulating neutrophils. This could be
due to-
• insufficient formation of neutrophils,
• reduced release of neutrophils from the bone marrow,
• a shortened neutrophil life span, and
• excessive neutrophil margination
The decrease in bone marrow levels could be due to -
(Coakley et al. and Kumakara et al.)
 anti-neutrophil antibodies,
 serum inhibitory factors directed against neutrophil precursors,
 suppressor action by cytotoxic T-cells, or
 phagocytosis of neutrophils within the bone marrow.

116. Oral manifestations
• oral ulceration
• stomatitis
• periodontitis ( rarely)

117. 3. Lazy leukocyte syndrome
• Lazy leukocyte syndrome is an extremely rare disorder that
manifests in both quantitative and qualitative neutrophil
defects.
• Lazy leukocyte syndrome is characterized by recurrent
infections due to both a deficiency in neutrophil chemotaxis
and a systemic neutropenia, while the phagocytic function of
the neutrophil remains intact.
• Within the bone marrow, the quantity and morphology of the
neutrophils are normal.

118. • Peripherally, however, there exists not only a severe
neutropenia but also functional defects of neutrophils with
regard to chemotaxis and random migration.
• There is a defect in the microtubular structure of neutrophils
which causes defective mobility.
• Impaired random and directional motility leads to a
diminished in vivo migration of neutrophils into the tissue and
to sites of inflammation.

119. Clinical findings
- Constantopoulous et al, 1975
Systemic findings
• high fever
• cough
• bilateral pneumonia
• purulent skin abscess
Oral manifestations
• stomatitis
• gingivitis
• recurrent ulcerations
• periodontitis with advanced
alveolar bone loss and tooth
loss.

120. Qualitative disorders
The neutrophil’s action can be divided into six stages or
functions:
• rolling along vascular endothelium,
• adherence to the endothelial lining,
• migration (chemotaxis) toward the site of the
infection,
• adherence to microorganisms,
• engulfment of bacteria (phagocytosis),
• intracellular killing.

122. Qualitaive Defects
1.Defects in rolling and adhesion –
LAD I and LAD II
2.Defects in migration and chemotaxis-
Hyperimmunoglobulin E syndrome, lazy leukocyte syndrome,
Papillon-lefvre syndrome, Down’s dsyndrome, Kindler
syndrome
3. Defects in phagocytosis and intracellular killing-
Chediak Higashi syndrome

123. I. Defects in the process of margination can
occur at two levels.
• The first is a defect in a specific neutrophil
ligand called the Sialyl-Lewis x (selectin)
protein (CD15s).
• A defect in this glycoprotein will result in the
loss of the neutrophil’s ability to ‘‘roll’’ along
the endothelial lining of venules.

124. • Alterations in the selectin-mediated rolling function prevent
the neutrophil’s egress from the venules.
• The defect is detected through flow cytometry using a
commercially available monoclonal antibody directed against
the membrane surface antigens associated with CD15s.
• The disease associated with this deficit is leukocyte adhesion
deficiency type 2 (LAD-II).

126. • The second neutrophil defect involving margination is at the
level of neutrophil adhesion to the endothelial cell.
• Defects in neutrophil surface integrins CD18/CD11a,
CD18/CD11b, and CD18/CD11c prevent the neutrophil from
adhering to the endothelium.
• Inability to adhere to endothelial cells prevents the migration
of neutrophils to the site of infection.

128. • These integrins are responsible for neutrophil
adhesion to opsonized bacteria and thus the
neutrophil’s ability to phagocytize bacteria is
compromised.
• Defects on CD18 and CD11 peptides are also
identified by flow cytometry.
• Deficiency of these intergrins is termed LAD-I.

129. Leukocyte adhesion deficiency
syndrome
• In 1979, a group of patients with similar
symptoms of delayed umbilical cord
separation and persistent bacterial infections
in the absence of pus formation were found to
share a common neutrophil motility defect.
• The name leukocyte adhesion deficiency was
given to this condition by Anderson & Springer
in 1986.

130. • Leukocytes adhere to vessel wall endothelium, other leukocytes,
and to complement via cell surface integrins.
• These integrins are protein complexes that are stored within
neutrophil granules and when activated, are found on the surface of
the neutrophil cell membrane.
• The initial studies on leukocyte adhesion deficiency patients found a
defect in the neutrophil integrins.
• Subsequent investigations into this disorder have identified two
types of leukocyte adhesion deficiencies, LAD-I and LAD-II.

131. LAD-I
• LAD-I is an inherited disorder that follows an autosomal recessive
pattern
• LAD-I is a disorder that involves a deficiency in three membrane
integrins.
• CD18/CD11a (LFA-1) binds to leukocytes and to endothelium via
intercellular adhesion molecules (ICAM).
• CD18/CD11b (Mac-1) binds to ICAM and complement and
facilitates complement- mediated phagocytosis.
• The function of CD 18/Cd11c is not known.
(OMIM 116920)

132. • The deficiency of these integrins prevents the neutrophil from
adhering to the vessel wall at the site of an infection.
• Therefore, in spite of a leukocytosis (20,000–80,000 cells/ml),
neutrophils are unable to migrate into the affected tissues.
• The clinical appearance is one of ulceration and necrosis of
tissue, but without signs of purulence.

133. Oral manifestations (Waldrop et
al.)
• acute gingival
inflammation of the
primary and permanent
dentition
• gingival proliferation
• gingival recession
• mobility of teeth
• pathological migration

134. The oral findings in a LAD-I pt.

135. LAD-II (OMIM 266265)
• LAD-II was first described in 1992 by Etziomi et al. Individuals with
LAD-II are characterized by short stature, mental retardation, and
craniofacial abnormalities as well as recurrent infections.
• The neutrophil defect in LAD-II is of the sialyl-Lewis x glycoprotein
(CD15s), which allows neutrophils to attach to selectins (CD62E) on
the endothelial surface.
• The end result is similar to LAD-1, and neutrophils are unable to
migrate extravascularly .
• While the oral condition of these patients has not been reported, it
can be assumed that the neutrophil defect is such that severe
periodontal disease and tooth loss is likely.

136. II. Deficits in neutrophil chemotaxis
• Deficits in neutrophil chemotaxis can be either inherited, or
secondary to a number of other neutrophil defects caused by a
variety of diseases or medications.
• Any alteration in the neutrophil cytoskeleton or its ability to
sense or respond to a chemotactic gradient will interfere with
the cell’s ability to reach the site of infection.
• Neutrophil chemotactic deficits are diagnosed in vivo through
the use of the Rebuck skin window or in the laboratory using a
Boyden chamber or the agarose technique.

137. 1. Hyperimmunoglobulin E syndrome (Hill-Quie syndrome,
Jobs syndrome) (OMIM 147060)
• Hyperimmunoglobulin E syndrome is a
multisystem disorder inherited as an
autosomal dominant trait that affects the
dentition, the skeleton, connective tissues,
and immune system .
• Classically, it has been characterized by a triad
of symptoms including skin abscesses,
pneumonia, and elevated serum
immunoglobulin E levels.

138. Clinical features
• Eosinophilia, candidiasis, arthritis, chronic eczematoid
dermatitis and other recurrent infections are also common .
• Typically, patients with hyperimmunoglobulin E syndrome
have coarse facial skin with prominent pores.
• Other common findings include facial asymmetry, prominent
forehead, deep-set eyes, broad nasal bridge and mild
prognathism.
• A decrease in bone density is common, leading to a high
incidence of long bone fractures .

139. Clinical features
• Clinically, the appearance of the soft tissue lesions is rather
unique.
• Often described as ‘‘cold abscesses’’, these deep soft tissue
lesions present as fluctuant masses that may be mistaken for
cysts or tumors.
• These abscesses, typically caused by S. aureus, often lack the
usual signs of inflammation, such as warmth, erythema, and
tenderness.
• Extension of these lesions into bone may occur giving rise to an
osteomyelitis.
• Recurrent infection is one of the chief features of
hyperimmunoglobulin E syndrome.

140. Three hypotheses exist for the chemotactic defect in the
neutrophils:
• A specific IgE against an infecting bacterium (S. aureus) causes
the release of histamine that may inhibit neutrophil
chemotaxis – Chikazawa et al, 1984
• Bacterial antigens cause monocytes to secrete chemotaxis
inhibiting mediators or IgG – Seligmann BE, 1983
• Mononuclear cells may create a specific factor which inhibits
neutrophil chemotaxis – Donabedian H, et al, 1982
Certainly contributing to the high rate of recurrent
infections in hyperimmunoglobulin E patients is a
defect in neutrophil chemotaxis

141. Oral manifestations
– ulcerations
– gingivitis
– over-retention of primary teeth
(Failure to shed the primary dentition in this case,
in contrast with the early loss of primary teeth
due to periodontitis seen in other disorders of
host defenses, is surprising

142. 2. Papillon-Lefèvre syndrome
(OMIM 245000)
• The Papillon-Lefevre syndrome is described as
a diffuse palmoplantar keratosis associated
with aggressive periodontitis of both primary
and permanent dentitions.
• The syndrome is named after the two authors
who first introduced this condition to the
literature in 1924.

143. • Papillon-Lefevre syndrome is a rare autosomal recessive
disease with a prevalence of one to three cases per million in
the general population.
• Consanguinity between parents has been reported in at least
one third of the reported cases.
• The syndrome appears equally in males and females

144. The two essential features of Papillon-Lefevre syndrome are
1.hyperkeratosis of the palms and soles (either diffuse
or localized)
2. generalized rapid destruction of the periodontal
attachment apparatus resulting in premature loss of
both primary and permanent teeth.

145. Other findings are-
• ectopic calcifications of the falx cerebri and
choroid plexus
• increased susceptibility to infection
• mental retardation
• endocrine disorders

146. • Papillon-Lefevre syndrome is but one of at
least 19 different forms of palmoplantar
keratoedema.
• While some of these other conditions may
manifest with abnormalities of the teeth,
Papillon-Lefevre syndrome is the only one
associated with aggressive periodontitis.

147. • The association of Papillon-Lefevre syndrome with aggressive
periodontitis, and in some cases recurrent infections, led
investigators to study neutrophil functions in Papillon-Lefevre
syndrome patients.
• Van Dyke et al. described neutrophil chemotaxis defects in
two patients with Papillon-Lefevre syndrome and noted
decreases in both random migration and directed migration
toward a chemotactic factor.

148. • This alteration of polymorphonuclear neutrophil leukocyte
function has not been observed in all cases.
• Both Lyberg and Schroeder et al. reported normal neutrophil
function including margination, chemotaxis, phagocytosis,
degranulation of lysosomes and intracellular destruction in
several children with Papillon-Lefevre syndrome who did not
exhibit an increased susceptibility to infection

149. 3. The Haim-Munk syndrome
(OMIM 245010)
• A particular form of Papillon-Lefevre syndrome has been
named the Haim-Munk syndrome. While also characterized by
palmoplantar keratosis and severe early onset periodontitis,
the Haim-Munk syndrome additionally presents with digital
abnormalities.
• These include osteolysis of the distal phalanges, abnormal
length and slenderness of the fingers and toes, and a claw-like
hypertrophic deformity of the nails

150. 4. Down’s syndrome
• Down’s syndrome, one of the most common causes of mental
retardation in children, was named after the English physician
who in 1866 characterized the appearance and behavior of
these patients.
• The distinct similarities in the features and conditions of the
disease led early researchers to suspect a chromosomal
aberration, and in the late 1950s Down’s syndrome was
specifically linked to trisomy of chromosome 21.

151. Down’s syndrome and
periodontitis
• In an extensive review of periodontal disease in Down’s syndrome, Roland-
Bousma & Van Dijk examined both endogenous conditions and exogenous
factors that may predispose affected patients to aggressive periodontitis.
• They divided the exogenous factors into local factors, related mostly to oral
hygiene, and secondary factors, such as tongue thrust, malocclusion, and lack of
lip seal, which are common features of Down’s syndrome.
• While certainly contributing to the extent of the disease, the bulk of the
evidence suggests that these exogenous factors are not commensurate with the
severity of the periodontitis noted in Down’s syndrome patients.

152. Among the endogenous factors that may exacerbate the
periodontitis in Down’s syndrome are defects in
neutrophils.
• the tendency of the nucleus in neutrophils of Down’s
syndrome patients to be consistently less segmented than in
other patient groups.
• preponderance of younger cell forms that is independent of
both the total leukocyte count and the relative number of
neutrophils.
• tendency for the shortening of the half-life of circulating
neutrophils in patients with Down’s syndrome.

153. Other Neutrophil defects reported
-
• significant reduction in chemotaxis in the
Down’s syndrome children.
• Reports on the phagocytic ability of
neutrophils in Down’s syndrome are mixed.
• Reduced bacteriocidal capacity has been
reported for a number of organisms, including
S. aureus, Escherichia coli, and C. albicans.

154. • Halinen et al. found increased levels of
neutrophil collagenase (MMP-8) in the saliva
and gingival crevicular fluid of Down’s
syndrome patients.
• These findings suggest that the active MMP-8
derived from triggered neutrophils and/or
cytokine induced periodontal fibroblasts may
reflect the periodontal destruction seen in
patients with Down’s syndrome.

155. Clinical features
• Clinically the gingiva are
red, swollen and bleed
easily.
• Gingival hyperplasia can
occur secondarily due to
mouth breathing, poor
hygiene, and local irritating
factors.

156. • The gingivitis frequently
progresses to generalized
early periodontitis, which
commences in the
deciduous dentition and
continues to affect the
permanent dentition. Bone
loss, migration of teeth and
mobility are common. All
these predispose to
premature loss of teeth.

157. • Macroglossia, fissured and geographic tongue, high
arched palate, cleft palate, delayed tooth eruption
and hypoplastic teeth are the most frequent oral
lesions
• Follicular hyperkeratosis, facial flushing, aloepecia
aerata and dry skin are common.
• Polydactyly, syndactyly, clinodactyly,
hyperextensibility of joints, other skeletal
abnormalities, congential heart abnormalities,
hormonal abnormalities, learning disabilities,
mongoloid slanting of eyes, short ears and a flat
face are common.

158. 5. Kindler syndrome
• Also called hereditary acrokeratotic poikiloderma, this
autosomal-recessive condition, first described by Kindler in
1954, is caused by mutation in the kinderlin gene (KIND1) .
• Kinderlin is expressed in multiple tissues, including the skin,
where it may play a role in integrin signaling of cell-adhesion
processes.
• Studies of the KIND1 gene homologue in the nematode
(roundworm) Caenorhabiditis elegans suggest that it has an
important role linking the actin cytoskeleton to the extracellular
matrix

159. • Patients present with severe periodontitis of both the primary
and secondary dentition, resulting in severe alveolar bone loss
and premature exfoliation of the teeth .
• Kindler syndrome manifestations include multiple
dermatological findings, including sun sensitivity, eczematoid
dermatitis, skin fragility, patchy hyper and hypo-pigmentation,
hyperkeratosis of the palms and soles, and diffuse skin
wrinkling.
• Ridging and grooving of the nails may also be present.

160. 6. Hypotrichosis osteolysis periodontitis palmoplantar
keratoderma syndrome (OMIM 607658)
• Hypotrichosis osteolysis periodontitis
palmoplantar keratoderma syndrome is a very
rare condition that resembles Papillon–Lefevre
syndrome and Haim– Munk syndrome.
• The condition has only been reported in three
individuals from two different families and
may be transmitted as an autosomal
dominant trait.

161. • It has been noted that periodontitis and gingivitis occur in
hypotrichosis osteolysis periodontitis palmoplantar
keratoderma syndrome, although the teeth are reported to
have been extracted in one patient as a result of advanced
caries.
• Radiographic demonstration of periodontitis is not provided
in reports of hypotrichosis osteolysis periodontitis
palmoplantar keratoderma syndrome.
• More thorough evaluation of periodontal status in
hypotrichosis osteolysis periodontitis palmoplantar
keratoderma syndrome is warranted.

162. III. Defects in intracellular killing
• Defects in intracellular killing usually refers to
degranulation defects
• Degranulation is either delayed or
incomplete, leading to impaired intracellular
killing.
• There are two main conditions with defects
in degranulation – Chediak- Higashi
syndrome and specific granule deficiency.

163. 1. Chediak-Higashi syndrome
(OMIM 214500)
• Chediak-Higashi syndrome is a rare autosomal
recessive disorder that primarily affects
neutrophils.
• Its genetic etiology manifests itself early in life
in the form of partial oculocutaneous
albinism, photophobia, frequent pyogenic
infections and lymphadenopathy.

164. Clinical features
• Oral findings include severe gingivitis, ulcerations
of the tongue and buccal mucosa, and early onset
periodontitis leading to premature loss of both
deciduous and permanent dentitions.
• The syndrome was first described by Beguez-
Cesar in 1943, but acquired its name 10 years
later from separate reports by Chediak in 1952
and Higashi in 1954, which described the same
condition

165. Clinical features
• Clinically, the syndrome may present as abnormalities of
pigmentation, recurrent infections, and bleeding tendencies .
• Oculocutaneous albinism can affect the skin, eyes, and hair.
• Hair color is characteristically metallic silver, the skin color white to
gray due to defective melanosomes, and the eyes are affected by
reduced pigmentation of the retina and iris.

166. Clinical features
• Other ocular abnormalities can include nystagmus, photophobia
and reduced visual acuity.
• Infections are commonly skin abscesses, pneumonias, otitis media
and sinusitis.
• Bleeding problems arise because of organelle abnormalities within
platelets that inhibit normal clot formation.
• Peripheral or cranial neuropathies may develop similar to those
seen in Parkinson’s disease.
• Weakness, sensory deficits, clumsiness, a wide-based gait, seizures
and tremors have also been reported

167. Cellular level findings
• On a cellular level, organelle abnormalities,
specifically of lysosomes, are present in cells
throughout the body.
• One of the hallmarks of the Chediak- Higashi
syndrome is the presence of large intracellular
azurophilic inclusions in the cytoplasm of
neutrophils.

168. Cellular level findings
• These large inclusions impair neutrophil migration, possibly by
inhibiting cell deformability, and render neutrophils unable to
metabolize and digest microbes.
• As a result, patients with Chediak- Higashi syndrome are
prone to recurrent infections in early childhood
• a mutation in the LYST (lysosome trafficking regulation) gene,
the only known Chediak-Higashi syndrome-causing gene, may
be responsible for this phenomenon. Bone marrow
transplantation appears to be the most effective treatment.

169. Oral manifestations
• dental pain
• swollen gingiva with frank purulence
• severe horizontal bone loss
• lymphadenopathy
- Delcourt-Deburyne, 2000
• severe mobility of teeth
• generalized recession with deep probing depths
- Hamilton RE, 1974
• gingival bleeding
– Huizing M et al, 2001

170. B. connective tissue disorders
Ehlers–Danlos syndrome
• The Ehlers–Danlos syndromes are a heterogeneous group of
inherited connective tissue disorders characterized clinically by skin
fragility, skin hyperextensibility, joint hypermobility, and excessive
bruising.

171. • At least 17 different subtypes of Ehlers– Danlos
syndrome have been classified based on genetic,
biochemical, and clinical characteristics
• Poor wound healing is a component of a number
of subtypes of Ehlers–Danlos syndrome, and
severe, early-onset periodontitis has been
associated with two subtypes: Ehlers–Danlos
syndrome type 4 and Ehlers–Danlos syndrome
type 8.

173. Ehlers–Danlos syndrome type IV (OMIM 130050)
- Sack’s ecchymotic type
• Transmitted as an autosomal-dominant trait, Pope
et al. (96) first identified that this form of Ehlers–
Danlos syndrome is caused by defects in type III
collagen.
• The majority of mutations that give rise to Ehlers–
Danlos syndrome type IV are point mutations that
result in substitution of a glycine residue within
the triple helix and point mutations that alter
splice junctions and lead to exon-skipping.

174. • These types of mutations disrupt the secretion of most of the
type III procollagen molecules being synthesized.
• The severity of the phenotype appears to be related to the
stability of mutant type III collagen protein and the extent to
which it disrupts collagen fibrillogenesis in the extracellular
matrix
• Since collagen type III comprises 9% of the gingival collagen
and approximately 16-20% of the total collagen in the
periodontal ligament, it was proposed that a defect in type III
collagen would compromise the periodontal attachment
apparatus.

175. The clinical presentation of Ehlers–Danlos
syndrome type IV can include
• significant and life-threatening cardiovascular and
cerebrovascular complications that predispose to rupture of
arteries, the bowel, and the gravid uterus .
• Phenotypic findings include short stature, pinched thin nose,
thin lips, lobeless ears, keratoconus, periodontitis, mitral valve
prolapse, intracranial aneurism, pneumothorax, uterine
prolapse, bladder prolapse, hypermobility of distal
interphalangeal joints, acroosteolysis, fragile skin, easy bruising,
cigarette-paper scars, and prominent venous markings.

176. • A number of reports document the presence of severe
periodontitis in individuals with Ehlers–Danlos syndrome type IV,
although many clinical reports of the condition do not mention if
an oral examination was performed, possibly because attention
was focused on more serious clinical manifestations
• More work needs to be done to determine the nature of the
cellular and biochemical defects in patients with early
periodontitis and Ehlers-Danlos syndrome.

177. Ehlers–Danlos syndrome type VIII (OMIM
130080) -Periodontitis type
• Transmitted as an autosomal-dominant condition, the gene
mutations responsible for Ehlers–Danlos syndrome type VIII
have not yet been identified.
• However, genetic linkage studies indicate that at least two
genetically distinct forms of Ehlers–Danlos syndrome type VIII
exist, with one form localized to chromosome 12 .
• The association of precocious periodontitis with Ehlers–Danlos
syndrome type VIII has been reported by a number of
investigators, suggesting that periodontal findings may be more
common in Ehlers–Danlos syndrome type VIII than in type IV.

178. • The association of
precocious periodontitis
with Ehlers–Danlos
syndrome type VIII has been
reported by a number of
investigators, suggesting
that periodontal findings
may be more common in
Ehlers–Danlos syndrome
type VIII than in type IV.

179. AIDS

180. AIDS
• Stands for Acquired Immuno Deficiency Syndrome
• This is the end stage disease in a patient with HIV infection
representing the irreversible breakdown of immune defence
mechanisms, leaving the patient a prey to progressive
opportunistic infections and malignancies.
• The definition of AIDS has now been broadened to include all
seropositive persons (irrespective of clinical manifestations) with
CD4 T cell counts of less than 200 per cu.mm

181. • The clinical severity of AIDS varies with the type of
infection or malignancy present.
• In early AIDS, many patients are ill only during
episodes of infection, which may respond to
treatment.
• Between episodes they may be relatively well and
able to resume normal life.
• The illness progresses inexorably and death ensues in
months or years.

182. CDC Surveillance Case Classification (1993):
Category A includes patients with acute symptoms or asymptomatic
diseases, along with individuals with persistent generalized
lymphadenopathy, with or without malaise, fatigue, or low-grade
fever.
Category B patients have symptomatic conditions such as
oropharyngeal or vulvovaginal candidiasis; herpes zoster; oral hairy
leukoplakia; idiopathic thrombocytopenia;or constitutional
symptoms of fever, diarrhea, and weight loss.
Category C patients are those with outright AIDS as manifested by life-
threatening conditions identified by CD4+ T lymphocyte levels of
less than 200 per cubic millimeter.

183. According to the system most affected patients present
with various complaints, some of which are as follows:
a. Respiratory system- The commonest presentation is with increasing dry cough,
dyspnea and fever.
b. Gastrointestinal system – Dysphagia, intestinal infections, Chronic colitis
c. CNS- opportunistic infections- toxoplasmosis and cryptococcosis
d. malignancies- Kaposi’s sarcoma
e. Cutaneous lesions - herpes lesions, candidiasis, xeroderma, seborrheic dermatitis,
prurigo, folliculitis, impetigo and molluscum contagiosum

184. ORAL AND PERIODONTAL MANIFESTATIONS OF
HIV INFECTION
• Oral Hairy Leukoplakia
• Oral Candidiasis
• Kaposi's Sarcoma
• Bacillary (Epithelioid)
Angiomatosis
• Oral Hyperpigmentation
• Atypical Ulcers and Delayed
Healing
• Adverse Drug Effects
• Periodontal D’se-
• L.G.E
• N.U.G
• N.U.P
• N.U.S

185. Oral Hairy Leukoplakia
• Oral hairy leukoplakia
primarily occurs in persons
with HIV infection.
• Found on the lateral
borders of the tongue, it
frequently has a bilateral
distribution and may extend
to the ventrum.

186. • This lesion is characterized by an asymptomatic, poorly
demarcated keratotic area ranging in size from a few
millimeters to several centimeters.
• Often, characteristic vertical striations, imparting a corrugated
appearance, are present, or the surface may be shaggy and
may appear "hairy" when dried.
• The lesion does not rub off and may resemble other keratotic
oral lesions.

187. Oral Candidiasis
• Candidiasis is the most common oral lesion in HIV diseases
and has been found in approximately 90% of AIDS patients.
• It usually has one of four clinical presentations:
pseudomembranous, erythematous, or hyperplastic
candidiasis or angular cheilitis.
• Although candidiasis in HIV-infected patients may respond to
antifungal therapy, it is often refractory or recurrent.

188. Kaposi's Sarcoma
• Kaposi's sarcoma is a rare, multifocal, vascular
neoplasm; it was originally described in 1872
as occurring in the skin of the lower
extremities of older men of Mediterranean
origin.
• Although KS is a malignant tumor, in its classic
form it is a localized and slowly growing
lesion.

189. • In the early stages, the oral lesions
are painless, reddishpurple macules
of the mucosa.
• As the lesions progress, they
frequently become nodular and can
easily be confused with other oral
vascular entities such as
hemangioma, hematoma, varicosity,
or pyogenic granuloma (when
occurring in the gingiva).

190. Bacillary (Epithelioid) Angiomatosis
• Bacillary (epithelioid) angiomatosis (BA) is an infectious
vascular proliferative disease with clinical and histologic
features very similar to those of KS.
• BA is believed to be caused by rickettsia-like organisms,
Bartonellaciae henselia, quintana, or others.

191. • Gingival BA manifests as red, purple, or blue edematous soft
tissue lesions that may cause destruction of periodontal
ligament and bone
• The condition is more prevalent in HIV-positive individuals
with low CD4 levels.

192. Linear Gingival Erythema
• A persistent, linear, easily bleeding,
erythematous gingivitis (LGE) has been
described in some HIV-positive patients.
• This may or may not serve as a precursor to
rapidly progressive necrotizing ulcerative
periodontitis
• LGE is often unresponsive to corrective
therapy, yet such lesions may undergo
spontaneous remission.

193. Necrotizing Ulcerative Gingivitis
• Some reports have described an increased incidence of
necrotizing ulcerative gingivitis among HIV-infected individuals,
although this has not been substantiated by other studies.

194. Necrotizing Ulcerative Periodontitis
• A necrotizing, ulcerative, rapidly progressive
form of periodontitis occurs more frequently
among HIV-positive individuals.
• NUP is characterized by soft tissue necrosis,
rapid periodontal destruction, and
interproximal bone loss
• Lesions may occur anywhere in the dental
arches and are usually localized to a few teeth,
although generalized NUP is sometimes present
after marked CD4+ cell depletion

195. Conclusion
• It is well established that many systemic conditions express
their effects on the periodontium.
• Future epidemiological studies designed to assess the role of
systemic conditions and disorders in periodontal disease are
needed, particularly to refine experimental design and data
analysis; to identify gaps in knowledge with respect to
mechanisms of factors known to play a role in increasing
susceptibility to periodontal disease; and to address gaps in
knowledge of the correlation with the systemic conditions
suspected of being related to periodontal disease.

196. References
• Carranza’s clinical periodontology-8th edition- Takei, Newman, Klokkevold
and Carranza
• Carranza’s clinical periodontology-9th edition- Takei, Newman and Carranza
• A textbook of oral pathology- 4th edition- Shafer, Hine and Levy.
• Drugs, diseases and the periodontium- Robin A Seymour
• Periodontal manifestations of local and systemic diseases- Laskaris G, Scully
C.
• Influences of systemic diseases on periodontitis in children and adolescents
- Joerg Meyle & Jose R. Gonzales Periodontology 2000, vol. 26, 2001, 92–
112

197. References
• Systemic disease and periodontitis: manifestations of neutrophil
dysfunction- David E. Deas, Scott A. Mackey & Howard T. McDonnell-
Periodontology 2000, vol. 32, 2003, 82–104
• Gingival and periodontal aspects of diseases of the blood and blood
forming organs and malignancy- Stephen r. Porter Periodontology 2000,
vol. 18, 1998, 102-110
• Mendelian forms of periodontitis- Thomas C. Hart & Jane .C. Atkinson-
Periodontology 2000, vol. 45, 2007, 95–112
• www.ncbi.nlm.nih.gov
• www.whonamedit.com/synd.cfm/3648.html
• www.wikepedia.com

198. Thank you