SYN= TOGETHER ,DROMOS= A RUNNING “The aggregate of signs & symptoms associated with any morbid process & constituting together the picture of the disease and related to each other anatomically, biochemically or physiologically” A group of deformations and malformation sequences, etc. that occur together due to some identifiable underlying cause. Syndromes can be caused by chromosomes anomalies, single genes mutations, teratogens, or other causes.

1. Head And Neck Syndrome
Dr Amitha G
Dept of oral pathology

2. INTRODUCTION
SYN= TOGETHER ,DROMOS= A RUNNING
• “The aggregate of signs & symptoms associated with any morbid process &
constituting together the picture of the disease and related to each other
anatomically, biochemically or physiologically”
• A group of deformations and malformation sequences, etc. that occur together due to
some identifiable underlying cause.
• Syndromes can be caused by chromosomes anomalies, single genes mutations,
teratogens, or other causes.

3. CLASSIFICATION OF SYNDROME
1. Etiologic classification
2. Embryologic or Histologic classification
3. Syndrome prototypes
4. Polythetic classification
5. Monothetic classification
6. Mixed classification
7. Morphogenetic classification

4. ETIOLOGIC CLASSIFICATION
Syndromes can be classified according to broad etiologic categories such as
• Monogenic
• Chromosomal
• Environmentally induced
Such classifications usually requires supplementary categories such as
• Multifactorial
• Disruptive
• Unknown

5. EMBRYOLOGIC / HISTOLOGIC CLASSIFICATION
Developmental disturbances of the tissue structure are basis of some classifications.
Thus hematoneoplastic syndromes are sometimes classified on the basis of the Germ layer
involved.
Examples
1. Multiple osteochondromas involves only one germ layer -The Mesoderm.
2. Gardner syndrome –consisting of polyposis of colon, osteomas, desmoid tumors,
leiomyomas, lipomas and odontomas involves – All 3 Germ Layers

6. SYNDROME PROTOTYPES
Syndromes can be analysed at different levels of organization.
In the broadest possible context, four classes of syndromes can be defined.
• Dysmetabolic syndrome
• Dyshistogenetic syndrome
• Malformation syndrome
• Deformation syndrome

7. MONOTHETIC CLASSIFICATION
In monothetic classification, syndromes are grouped together because they share a single
feature such as polydactyly or cleft palate.
Such groupings are often used as an aid in differential diagnosis.
Examples:
1. Syndromes with arthrogryposis
2. Syndromes with craniosynostosis
3. Syndromes with propensity for Wilms tumor

8. LIST OF SYNDROMES ACCORDING TO ORAL CAVITY SITE
LIPS
Double lip -> Aschers’s syndrome
Pebbly lesions of lip -> Cowden’s syndrome
Everted lip -> Down’s syndrome
Fusion of upper lip to maxillary gingiva -> Ellis-Van Creveld syndrome
Thick lips -> Hurler syndrome
Pigmented Lips -> Laugier - Hunziker syndrome
Neuromas Of Lip -> Multiple endocrine neoplasia syndrome (Type 3)
Cleft Lip -> Goltz Gorlin syndrome
Protruding Lip -> Reiger’s syndrome
Occurrence Of Pits Of Lip -> Van Der Woude’s syndrome
Whistling Lips -> Whistling face syndrome
Dryness And Fissuring Of Lips -> Mucocutaneous lymph node syndrome

9. BUCCAL MUOSA
Lichen Planus Lesions On Buccal Mucosa
• Graham Little syndrome
• Grinspan syndrome
Bilateral Oral White Lesion
• Jadassohn Lewandowsky syndrome
Neuromas of Buccal Mucosa
 Multiple Endocrine Neoplasia syndrome
Oral Leukoplakia
• Zinsser –Engman – Cole syndrome

10. TONGUE
Macroglossia -> Down’s syndrome
Microglossia ->Hanhart’s syndrome
Aglossia -> Hypoglossia –Hypodactilia syndrome
Fissured Tongue -> Melkerssons Rosenthal syndrome
Glossitis -> Chediak-Higashi syndrome
Hypotomia Invoving Tongue -> Floppy Infant syndrome
Multiple Hemangiomas -> Maffucci’s syndrome
Atrophy of tongue -> Parry –Romberg syndrome
Glossoptosis -> Pierre Robin syndrome

11. PALATE
High palatal vault
• Apert’s syndrome
• Crouzon syndrome
• Down’s syndrome
• Marfan syndrome
• Treacher Collin syndrome
Cleft palate
• Pierre Robin syndrome
• Goltz gorlin syndrome
Pebbly Lesions of palate
• Cowden’s syndrome

12. GINGIVA
Severe Gingivitis -> Chediak –Higashi syndrome
Pebbly Lesions Of Gingiva -> Cowden’s syndrome
Gingival Enlargement -> Cross syndrome
Gingival Fibromatosis -> Ramon syndrome
Inflammatory Gingival Enlargement -> Papillon –Lefevre syndrome
Congenital Enlargement Of Gingiva -> Rutherfurd’s syndrome
Massive Growth Of Gingiva -> Sturge –Weber syndrome

13. TEETH
Microdontia
• Down’s syndrome
• Gardner’s syndrome
• Goltz-Gorlin syndrome
Macrodontia -> KBG syndrome
Hypodontia -> Down’s syndrome
Altered Eruption -> Turner’s syndrome
Congenital missing teeth
• Curry-hall syndrome
• Bloch –Sulzberger syndrome
Absence Of Premolars And Third Molar -> Book’s syndrome
Additional Cusps -> Ellis-Van creveld syndrome

14. Peg or cone shaped teeth
• Crouzen syndrome
• Curry-Hall syndrome
• Trichondental syndrome
Supernumenary Teeth
• Down’s syndrome
• Gardner’s syndrome
Taurodontism -> Trichodental syndrome
Talon’s cusp -> Rubinstein-Taybi syndrome
Enamel hypoplasia -> Ehlers-Danlos syndrome
Development Of Crack During excessive Occlusal Forces -> Cracked Tooth
syndrome

15. BONE
Micrognathia
Pierre robin syndrome
Turner’s syndrome
Fibrous dysplasia
Albright’s syndrome
Jaffe Lichenstein syndrome
Cortical thickening or hyperostosis
Caffey-Silverman syndrome
Mandibulofacial Dysostosis
Treacher Collins syndrome
Maxillary hypoplasia
Reiger’s syndrome
Scheuthauer-Marie-Sainton syndrome
Mandibular hypoplasia
Hutchinson Gilford syndrome
Cleft of Alveolar Process
Orofacial Digital syndrome
Elongated Styloid Process
Eagles syndrome

16. APERT SYNDROME
• Apert syndrome is named after the French physician “Eugene Apert”, who described the
syndrome Acrocephalosyndactylia in 1906.
• It is rare autosomal dominant disorder characterized by craniosynostosis (premature
fusion of cranial sutures), severe syndactyly of the hands and feet, symphalangism and
dysmorphic facial features.

17. ETIOLOGY
• Apert syndrome occurs as a result of mutation in Fibroblast
growth factor receptor 2 (FGFR2) on chromosome 10q25.3-
26.
• Fibroblast growth factor receptor 2 mutation leads to an
increase in the number of precursor cells that enter the
osteogenic pathway. Ultimately, this leads to increased
subperiosteal bone matrix formation and premature calvaria
ossification during fetal development.
• Syndactyly of Apert syndrome could be due to effect
mediated by keratinocyte growth factor receptor (KGFR).

18. CLINICAL FEATURES
• Incidence: Asians have the highest reported prevalence (22.3 per
million live births).
• one in 65,000 babies is born with Apert syndrome.
• Sex: No gender predilection.

19. Presentation
• It is characterized by severe craniosynostosis, craniofacial abnormalities and symmetric
syndactyly of the hands and feet.
• Syndactyly involving the hands and feet with partial-to-complete fusion of the digit, often
involving second, third and fourth digits. These often are termed mitten hands and sock feet.

20. ORAL MANIFESTATIONS
• The jaw shows a prominent mandible, maxillary
hypoplasia, drooping angle of the mouth and a
trapezoid shaped appearance to the lips when they are
relaxed.
• High arched palate, bifid uvula, cleft palate, crowded
upper teeth, malocclusion, delayed and ectopic
eruption, shovel shaped incisor, supernumerary teeth,
V-shaped maxillary arch and bulging alveolar ridges.
https://head-face-med.biomedcentral.com/articles/10.1186/1746-160X-3-10

21. TREATMENT AND PROGNOSIS
• Surgical care involves early release of the coronal sutures
and fronto-orbital advancement and reshaping.
- Release of skull bone fusion (craniosynostosis release)
- Midface advancement
- Correction of wide-set eyes (hypertelorism correction)
• The cosmetic and functional defects can be treated by an
interdisiciplinary approach using multiple surgical
procedures.
• Prognosis largely depends on the age at operation.
http://craniofacialcochin.com/apert-syndrome/

22. ASCHER’S SYNDROME
• Ascher’s syndrome is a rare disease first described in 1920 by Ascher, an
ophthalmologist from Prague.
• It is characterized by a double upper lip, blepharochalasis, and nontoxic thyroid
enlargement.

23. ETIOLOGY
• Etiology of this syndrome is unknown.
• Most cases are sporadic, though rarely family of Ascher has been reported.
CLINICAL FEATURES
• Double lip usually affects the upper lip and are rare oral anomaly of
congenital or acquired origin.
• Acquired cases of the syndrome usually result from trauma, while
congenital cases stem from a developmental anomaly.
• It is equally prevalent in both genders and also shows no racial
predilection.
• It usually affects the upper lip bilaterally, although it can also occur
unilaterally in both the upper and lower lips.

24. HISTOPATHOLOGY
Showing acanthosis in epithelium, minor mucus glands and skeletal muscles in connective tissue
http://www.ejgd.org/article.asp?issn=2278-9626;year=2014;volume=3;issue=3;spage=199;epage=201;aulast=Bakshi
An appraisal of congenital maxillary double lip with a case report

25. TREATMENT AND PROGNOSIS
• It is indicated when the condition interferes with speech and chewing, or for cosmetic reasons.
• Surgical techniques like W-plasty, electrosurgical excision
• Prognosis remained good, and no severe systemic problems have been seen.

26. BECKWITH SYNDROME
Wiedemann-Beckwith syndrome (WBS)
• It is a disorder of growth regulation exhibiting somatic overgrowth and a predisposition
to embryonal tumors.
• It is characterized by macroglossia, omphalocele, hypoglycemia, renomegaly,
microcephaly, hepatomegaly, splenomegaly

27. ETIOLOGY
Epigenetic and/or genetic alterations that dysregulate the imprinted genes on chromosome 11p15.5.
• The presence of chromosomal aberrations and gene mutations on a part of chromosome 11, have pointed
to genetic factors, as the probable cause of Beckwith-Wiedemann Syndrome
• Chromosome 11 of the child is affected, as certain expressions of the parent gene (mother's or father's)
remain inactive; a process known as genetic imprinting
• Sometimes, these defective genes are inherited from the parents, or sometimes normal genes stop
functioning in the prenatal stage sporadically, leading to BWS.
https://www.dovemed.com/diseases-conditions/beckwith-wiedemann-syndrome-bws/

28. Epidemology
Age and Sex Distribution
•The global incidence is about 1 in 14,000, and 85% of the cases occur at random (sporadic
occurrences)
•There is no known predilection towards any particular gender or racial group

29. Signs and Symptoms
• Major features: Abdominal wall defects causing internal
organs to push themselves out of the belly button, large-
sized tongue , abnormally large body at birth
• Minor features: Creases at the earlobes, blood vessel
defect called port-wine stain (often seen as a red
birthmark), hypoglycemia, renomegaly, asymmetrical
body
• Infant may have large eyes, undescended testicles,
microcephaly, hepatomegaly, splenomegaly, be lethargic,
and convulsions

30. LABORATORY FINDINGS
On physical examination, a child should be present with more than
two major and three minor features to be defined as affected with
Beckwith-Wiedemann Syndrome.
Diagnostic tools include:
• Evaluation of patient’s medical history
• Blood tests for electrolytes
• Genetic analysis
• MRI, CT scan (abdominal)
• X-ray studies (of the skeletal system)
• Abdominal ultrasound scan
https://www.dovemed.com/diseases-conditions/beckwith-wiedemann-syndrome-bws/

31. TREATMENT
The management of BWS patients involves standard supportive medical and surgical strategies
(eg, surgical repair of omphalocele).
http://www.afrjpaedsurg.org/viewimage.asp?img=AfrJPaediatrSurg_2011_8_2_159_86053_f6.jpg
(a) Infected omphalocele, (b) good granulation tissue, (c) healed ventral hernia

32. BEHCET’S SYNDROME
Oculo-oro-genital syndrome
• Behçet’s syndrome was described by the Turkish dermatologist Hulûsi Behçet.
• It is characterized by recurrent aphthous stomatitis, uveitis, genital ulcers, and skin lesions.

33. ETIOLOGY
• The underlying cause of Behçet's disease is unknown.
• As with other autoimmune diseases, disorder may represent aberrant immune activity triggered by exposure of
an agent, in patients with a genetic predisposition (HLA B51).
• Some environmental factors that have been suggested as possibly being associated with Behçet's disease
include:
• Herpes virus,
• Hepatitis virus,
• Bacteria,
• Pollutants e.g., industrial waste or chemicals.

34. EPIDEMIOLOGY
The higher prevalence is seen eastern Asia, where 1 in 10,000 , North America, where it is estimated that 1
in 500,000 persons is affected.
CLINICAL FEATURES
Age – Young adults common around 25 to 40years.
Sex predilection- Males are more common

35. Presentations – It is characterized by oral, genital ulcerations, ocular and skin lesions.
Disease is usually the appearance of oral lesions in about 25 to 70% of cases. The lesions are painful and very similar
clinically and histologically to that of recurrent aphthous ulcers.
They occur in crops at any intraoral sites and consist of ulcer ranging from several millimeters to centimeter or more
in diameter.
These ulcers have erythematous border and are covered by a grey or yellow exudate.

36. HISTOPATHOLOGICAL FEATURES
• The features are not specific for Behcet’s syndrome
and can be seen in aphthous stomatitis.
• The small blood vessels classically demonstrate
intramural invasion by neutrophils, karyorrhexis of
neutrophils, and extravasation of RBC and fibrinoid
necrosis of the vessel wall.
http://www.dxpath.com/histlib/Behcet-s-syndrome-histopathology-20373.html
https://escholarship.org/uc/item/81f3k4dj

37. TREATMENT AND PROGNOSIS
• Applications of corticosteroid treatment for recurrent ulcerations have been indicated for temporary relief and
to prevent further ulcerations.
• Mouthwashes with local anesthetic and use of painkillers like non steroidal anti-inflammatory drugs help in pain
relief.
• Corticosteroids are also used in the form of eye drops to reduce inflammation; they are also used during
involvement of the nervous tissue with other immunosuppressive agents.
• Immunosuppressive agents like Azathioprine, Chlorambucil help in reducing inflammation and protection of the
organ.
http://www.medindia.net/patientinfo/behcets-syndrome.htm

38. BURNING MOUTH SYNDROME
SYNONYMS: Stomatopyrosis, Somatodynia, Glossopyrosis, Glossodynia, Burning Tongue Syndrome
Burning mouth syndrome (BMS) is an idiopathic condition characterized by a continuous burning sensation
of the mucosa of the mouth, typically involving the tongue, with or without extension to the lips and oral
mucosa.

39. ETIOLOGY:
LOCAL FACTORS
Xerostomia
Chronic mouth breathing
Chronic tongue trust habit
Referred pain from teeth or tonsils
Atypical facial pain or neuralgia
Angioedema
Oral candidiasis
Temporomandibular dysfunction
Oral submucous fibrosis
Contact stomatitis
Trauma to lingual nerve
SYSTEMIC FACTORS
Vitamin B deficiency
Diabetes mellitus
Chronic gastritis or regurgitation
Chronic gastric hypoacidity
Hypothyroidism
Mercurialism
Estrogen deficiency
Anxiety, stress, depression
Parkinson’s diseases
AIDS
https://www.1800dentist.com/burning-mouth-syndrome/

40. Epidemiology
BMS appears to be most prevalent in postmenopausal women. It has been reported in 10
to 40 percent of women presenting for treatment of menopausal symptoms.
Age
BMS is particularly common among postmenopausal women aged over 55. It also affects
young adults older than 30 to 40 years.
Sex
BMS is much more frequent among women, with the male-to-female ratio ranging
between 1:7 and 1:13.
Site
The tongue is the most common site of involvement, but the lips and palate are also
frequently involved.

41. Signs & Symptoms
Burning mouth syndrome is a painful condition where the discomfort gets worse as the day progresses.
Because of this, in some cases individuals affected may experience:
• Dry mouth
• Pain
• Increased thirst
• Changes or loss of taste
• Metallic taste in mouth that remains after eating or brushing teeth
• Burning or scaled sensation in one or more areas of the mouth
https://draxe.com/burning-mouth-syndrome/

42. Risk Factors
Medical conditions that can cause burning mouth symptoms include:
• Sjogren’s Syndrome
• Radiation therapy
• Chemotherapy
• Low blood pressure medications
• Vitamin B deficiency
• Iron deficiency
• Acid reflux
• Diabetes
• Thyroid problems
• Fungal infection in the mouth
• Dentures that don’t fit properly
• Allergic reactions to dyes, foods, toothpaste, fragrances or environmental elements

43. Presentation
• Spontaneous onset, although it may be quite gradual.
• The dorsum of the tongue develops a burning sensation.
• Mucosal changes are visible, tongue have erythematous and
edematous papillae on the tip of the tongue.
• There is significant decrease in stimulated salivary output.
• Patient complains of xerostomia. Salivary levels of various
proteins, immunoglobulins and phosphates may be elevated
and there is decreased pH or buffering capacity.
• Along with other chronic discomforts, patients frequently
demonstrate psychologic dysfunction, usually depression,
anxiety or irritability.

44. TREATMENT
1. Low doses of tricyclic antidepressants
2. Selective serotonin reuptake inhibitors
3. Dual-action antidepressants
4. Antipsychotics
5. Benzodiazepines
6. Gabapentin 300-1600 mg/d (start with 100 mg)
7. Alpha-lipoic acid 600 mg/d

45. CHEDIAK –HIGASHI SYNDROME
• SYNONYMS: Beguez Cesar Syndrome, Chediak –Steinbrinck-Higashi
Syndrome
• Chediak-Higashi syndrome is a rare autosomal recessive disorder
which is characterized by incomplete oculo-cutaneous hypo-
pigmentation, neutropenia and an abnormal susceptibility to
cutaneous and respiratory infections.
• Hepatosplenomegaly, lymphadenopathy, pancytopenia, jaundice
and gingivitis with bleeding tendency are other common features.
• It was first described by Beguez Cesar in 1943, Steinbrinck in 1948,
Chediak in 1952, and Higashi in 1954.

46. ETIOLOGY
• Inefficient use of lysosomal enzymes resulting from a
mutation in the lysosomal trafficking regulator, or LYST
gene or CHS1 gene.
• The CHS1 gene affects the synthesis and/or maintenance
of storage or secretory granules in the cells.
• Example lysosomes of leukocytes and fibroblasts, dense
bodies of platelets, azurophilic granules of neutrophils,
and melanosomes of melanocytes.
Abnormalities of
granulation are also
seen in cytotoxic T-
cells as seen in this
lymphocyte with a
single large
azurophilic granule
Eosinophils
show
abnormally
giant
granules
Abnormalities of nuclear
lobation in neutrophils
as seen in this bi-lobed
neutrophil.
neutrophils
with giant
azurophilic
granules.
http://www.pathpedia.com/education/eatlas/histopathology/blood_cells/chediak-higashi_syndrome.aspx

47. CLINICAL FEATURES
• It is seen in all the races.
• Age- Common after birth or in children less than 5yrs.
• Presentation-Hypopigmentation resulting from the pigment dilution
is noted in skin and hair during infancy. The hair will have gray
streaks. Neuropathy and ataxia are prominent features in some
patients.
• The degranulation defect of neutrophils causes recurrent bacterial
infections of the skin and respiratory tract, chiefly by gram-positive
organisms, such as Staphylococcus aureus and β-hemolytic
Streptococcus.
• Patients usually die of recurrent infections before the age of 10 years.
https://askhematologist.com/chediak-higashi-syndrome/

48. Oral manifestations
Ulceration of the oral mucosa, severe gingivitis and glossitis is seen.
Periodontal breakdown was the common feature due to defective leukocyte function.

49. LABORATORY FINDINGS
• Laboratory investigation reveals decreased
haemoglobin, raised ESR, neutropenia and
lymphocytosis. Blood culture showed a growth of
staphylococcus aureus.
• On peripheral blood smear, giant granules are present
in neutrophils, eosinophils and granulocytes.
• Bone marrow biopsy reveals myeloperoxidase positive
inclusions in neutrophils and its precursors as well as
in monocytes and lymphocytes.
• Hair microscopy reveals multiple small pigmented
granules in the shaft.
Eosinophils
show
abnormally
giant
granules
neutrophils
with giant
azurophilic
granules.
Bone
marrow
aspirate
showing
giant
eosinophilic
granules
Evenly distributed
melanin granules of
regular diameter which
were bigger than those
seen in normal hair

50. TREATMENT AND PROGNOSIS
There is no specific treatment for the disease. it is often fatal, with death occurring
before the child reaches the age of 10 years.

51. COWDEN’S SYNDROME
• SYNONYMS: Multiple Hamartoma And Carcinoma Syndrome, Lhermitte –
Duclos Disease
• Cowden's syndrome is a rare autosomal dominant syndrome that is characterized
by hamartomas of ectodermal, mesodermal, and endodermal origin as well as
an increased risk of breast, thyroid, and endometrial neoplasias
ETIOLOGY
It is caused by mutation of PTEN (phosphatase and tensin homolog) gene.

52. CLINICAL FEATURES
Mucocutaneous lesions
a) Multiple facial papules
b) Dermal fibromas
c) Oral fibromas
d) Lipomas
e) Vascular malformations
f) Cutaneous and oral malignancies.
Oral manifestation
Papular and verrucous lesions of the lips, tongue, gingiva, alveolar ridge, buccal mucosa, palate and
tonsils have been seen. These lesions may coalesce and produce a cobblestone appearance.

53. HISTOPATHOLOGICAL FEATURES
• The oral lesions are rather nonspecific, essentially representing fibroepithelial hyperplasia.
• Other lesions associated with this syndrome have their own characteristic histopathologic findings,
depending on the hamartomatous or neoplastic tissue origin.
TREATMENT AND PROGNOSIS
• Treatment of multiple hamartoma is controversial. Although most of the tumors are benign, the
prevalence of malignancy is higher than in the general population.

54. HEERFORDT’S SYNDROME
SYNONYMS
Heerfordt's disease, Heerfordt-Mylius syndrome, Heerfordt-Waldenstrom syndrome.
Heerfordt syndrome is rare and is characterized by fever, uveitis, parotid gland enlargement, and facial
nerve palsy.
The condition was first described in 1909 by Danish ophthalmologist Christian Frederick Heerfordt.
It was originally attributed to mumps, but after further studies by Swedish doctor Jan G. Waldenström in
1937, it was classified as a distinct manifestation of sarcoidosis.

55. ETIOLOGY
The exact cause of Heerfordt's syndrome has not yet been definitively determined. It is been said that the syndrome
results from a combination of an environmental agent and a hereditary predisposition. Mycobacterium and
Propionibacteria species have both been suggested as the environmental agents.

56. CLINICAL FEATURES
Symptoms and Signs:
General
 The patient may have experienced paroxysmal episodes of fever or night sweats.
 Evidence of recent weight loss
 Facial swelling around the cheeks
 Swollen eyelids
 Inflamed eyes, squinting in light
 Visible facial nerve palsy with drooping of features on one side.

57. Ocular
 Acute uveitis presents with:
o Ocular discomfort
o Photophobia
o Blurred vision
o Red eye
 The lacrimal glands may be involved, causing puffy eyelids.
Parotid swelling
• May be unilateral or bilateral - bilateral in 73% of cases may cause sarcoidosis.
• Diffuse, painless swelling which is not tender on palpation.
• May cause a dry mouth.
• Tongue deviation or atrophy

58. Cranial nerve palsy
• Commonly affect the facial nerve (CN VII) which is abrupt in onset within a short period of the parotid
swelling.
• Sometimes the nerve is thought to be entrapped or infiltrated by granulomatous inflammation in the
parotid gland or facial canal, but exact site remains uncertain.
• Disturbance of taste due to chorda tympani dysfunction.
• Other cranial nerves can also be involved. Symptoms of other cranial neuropathies commonly involved in
neurosarcoidosis include:
• Disturbance of smell
• Blurred vision/diplopia/blindness
• Speech or swallowing difficulty
• Vertigo/deafness/tinnitus
• Weakness of trapezius/neck muscles
• Bell's phenomenon may be seen - upward, outward turning of the eyeball as the patient attempts to close
the eyelids.

59. INVESTIGATIONS
The two most useful specific diagnostic tests for this presentation of sarcoidosis are:
1. Serum Angiotensin Converting Enzyme (ACE) - which is usually elevated.
2. Scintigraphy using Gallium 67 - which shows increased uptake in the parotid gland, signifying active
sarcoidosis. Scintigraphy may reveal other sites of active sarcoidosis.
Additional investigations may include:
• Chest x ray - to look for evidence of hilar adenopathy or pulmonary involvement.
• Basic screening blood tests such as ESR, FBS, Urine examination and LFTs are usually performed as
baseline investigations but are fairly non-specific.
• Lumbar puncture may be needed where there is suspicion of meningitis - in sarcoidosis, it shows a sterile
pleomorphic inflammatory picture.

60. TREATMENT AND PROGNOSIS
• Sarcoidosis tends to undergo spontaneous remission in 50–60% of cases and does not always require
active management. Surgical intervention may be used to treat the complications of cataracts or
vitreous opacification. Uveitis increases the risk of glaucoma, so a significant proportion of patients
may require trabeculectomy or other glaucoma-drainage devices.
• The degree of involvement of sarcoidosis at other sites will influence the overall prognosis. Overall long-
term mortality in sarcoidosis is about 5-8%

61. HUNTER SYNDROME
SYNONYMS: Mucopolysaccharidosis II
Hunter syndrome is a rare, X-linked disorder caused by a deficiency of the lysosomal enzyme iduronate-2-
sulfatase, which catalyzes a step in the catabolism of glycosaminoglycans.
It was first described by Charles Hunter, a Canadian physician , in 1917.
ETIOLOGY
It is caused by a deficiency in the activity of the lysosomal enzyme exohydrolase iduronate-2-sulphate located
at Xq28.
This enzyme deficiency leads to intracellular and extracellular accumulation of glycosaminoglycan, dermatan
and heparin sulphate.

62. TYPES
 Type A mucopolysaccharidosis type II (MPS II) disease (severe form)
 Type B mucopolysaccharidosis type II disease (milder form)
CLINICAL FEATURES
Incidence : 1 in 170 000 male live births
Age: The severe form is diagnosed in children aged 2-4 years.
The mild form cannot be diagnosed until teenage or adulthood.

63. Presentation:
General Appearance
 Broad noses with flared nostrils
 Prominent supraorbital ridges
 Large jaws
 Thick lips
 Enlarged and protruding tongue.
 The head circumference is large throughout life
 Mobility is restricted because of joint stiffness and contractures.
Skeletal Abnormalities
• Abnormal thickness of all bones and irregular epiphyseal ossification in the joints.
• The hands shows claw-like Appearance
• Loss of hand function.
• The ribs are thickened and have an unusual shape and clavicles can be increased in bulk
• The lateral surfaces of the vertebral bodies are irregularly notched in appearance.

64. Ear, eyes and respiratory involvement
 Retinal dysfunction and bilateral pigmentary changes
 Disk swelling and scleral thickening, which may cause optic nerve compression
 Hearing loss
 Recurrent upper respiratory tract infections
 Recurrent otitis media
 Upper airway obstruction
 Sleep apnoea
 Recurrent ear infections
Gastrointestinal Involvement
Umbilical and inguinal hernias
Hepatosplenomegaly
Cardiovascular Involvement
Valvular thickening on echocardiography
Right And Left ventricular hypertrophy And heart Failure
Skin
Thickened and inelastic.
Ivory-white papules that are 2 to 10 mm in diameter, often coalescing to form ridges

65. Oral manifestations
 Peg shaped or irregularly shaped teeth
 Hyperplastic and hypertrophic gingiva
 Limited mouth opening
 Enlarged tongue
• Hypertrophic adenoids and tonsils

66. HISTOLOGIC FINDINGS
 Histologic examination of either peripheral granulocytes or bone marrow cells may reveal Alder-Reilly granulations.
When stained with toluidine blue, peripheral lymphocytes exhibit metachromatic granules within vacuoles.

67. TREATMENT AND PROGNOSIS
• Management has been palliative and focused on the treatment of signs and symptoms.
• Prognosis is poor and die at young age

68. HAND-SCHULLER-CHRISTIAN SYNDROME
SYNONYMS: Multifocal Eosinophilic Granuloma, Hand-Schuller-Christian Disease
It is a disease characterized by wide spread skeletal and extraskeletal lesions and a chronic clinical
course.
It is a rare entity comprising of exophthalmos, diabetes insipidus and geographical map skull.
It was first described by Hand in 1893 had bronzed skin, hepatosplenomegaly and poor development,
besides exophthalmos and geographic map skull. Schuller 1915 and Christians 1920 had called this a triad.
It was Rowland 1929 who gave histological description of this lesion in different organs while Green and
Farber 1942 demonstrated that eosinophilic granuloma of bone.

69. CLINICAL FEATURES
Age : common in young adults
Sex : more common in male of ratio 2:1
Presentation :
 Single or multiple areas of punched out bone destruction in the skull.
 Unilateral or bilateral exopthalmus.
 Diabetes insipidus with or without other manifestation of dyspituitarism such as polyuria dwarfism or
infantilism.
 Involvement of facial bones is frequently associated with soft tissue swelling and tenderness causing
facial asymmetry.
 Otitis media is common.
 Visceral organs may be involved.
Sometimes skin exhibits papular or nodular lesions

70. Oral manifestations:
 Sore mouth with or without ulcerative lesions.
 Halitosis
 Gingivitis
 Loose and sensitive teeth with precocious exfoliation
 Failure of healing of tooth sockets following extraction.
 Loss of bone

71. RADIOGRAPHICAL FEATURES
 Individual lesions with sharp outline, particularly in skull are seen
 Lesions in jaw appear more diffuse with destruction of alveolar bone and tooth displacement.

72. HISTOLOGICAL FEATURES
 Manifestations occur in four stages during the progression of the lesion
 These are:
1. A proliferative histiocytic phase with accumulation of eosinophilic leukocytes scattered throughout the sheets of
histiocytes.
2. A vascular-granulomatous phase with persistence of histiocytes and eosinophils sometimes with aggregations of lipid
laden macrophages.
3. A diffuse xanthomatus phase with abundance of foam cells.
A fibrous or healing phase.

73. TREATMENT AND PROGNOSIS
 The treatment of choice is curettage and excision of the lesions inaccessible lesions may be irradiated for some patients
chemotherapeutic drugs was benefited like prednisone, vinblastine and cyclophosphamide.
 The prognosis is good. Patient undergo spontaneous remission over a period of time.

74. MARFAN SYNDROME
SYNONYMS: Marfan- Achard Syndrome, Arachnodactyly
Marfan syndrome is an autosomal dominant heritable disorder of fibrous connective tissue that classically involves
3 systems: skeletal, ocular, and cardiovascular.
It was first described in 1896, by a French pediatrician named Antonin Marfan.
Former American President Abraham Lincoln (1809-1865) was thought to had Marfan’s syndrome.