Chapter 16-Derm Dz 2 Flashcards
prevalence of peutz-jeghers syndrome
1:50,000-200,000
What are 3 characteristic clinical manifestations/risks of peutz-jeghers?
- freckling of hands, perioral skin, oral mucosa
- hamartomatous intestinal polyps
- predisposition towards cancer 10-18x greater
inheritance of peutz-jeghers
autosomal dominant
What % of peutz-jegher cases represent new mutations
35%
Characteristic molecular change in peutz-jeghers
- chromsome
- encodes ____
- STK11 mutation also called LKB1
- chromosome 19p13.3
- encodes serine/threonine kinase
How do you tell the difference between an ephelide and a lesion of peutz-jeghers?
PJ lesions do not wax and wane with sun exposure
In addition to hamartomatous polyps of the jejunum and ileum (predominantly) PJ patients also are at increased risk of what intestinal complication?
intussusception- telescoping of the bowel
are patients with PJ at higher risk of GI adenocarcinoma?
yes- but unrelated to the polyps apparently
___% of women with Peutz-jeghers develop breast cancer by 60
50%
Histiologic appearance of pigmented lesion of peutz-jeghers intraorally
- acanthosis, elogated rete ridges
- elongated dendritic processes of melanocytes with pigment
- no increase in the # of melanocytes
Characterized by numerous vascular hamartomas of the skin and mucosa
Hereditary hemorrhagic telangiectasia (HHT)
Inheritance pattern of HHT? Alternate name?
autosomal dominant… OSLER-WEBER-RENDU Syndrome
Prevalence of HHT? Whats usually the first sign of HHT?
1:5000-18000…Epistaxis
Genetic mutations for:
- HHT1
- HHT2
- Overlapping syndrome of HHT and juvenile polyposis
- ENG (endoglin gene) chromo 9
- ALK1; ACVRL1 chromo 12
- MADH4
HHT1 characteristically affects what (2) organs more frequently than HHT2 which affects ____
HHT1: pulmonary (lungs) cerebral (brain)
HHT2: liver
patients with overlapping syndrome of MADH4 have an increased risk of _________ at an early age
colorectal carcinoma
Oral lesions of hereditary hemorrhagic telangiectasia consist of multiple small telangiectasias that most frequently involve which 3 sites?
- vermillion zone of the lips, 2.tongue and 3.buccal mucosa
GI telangiectasias of HHT tend to rupture and cause significant GI bleeding resulting in _____
chronic iron deficiency anemia
Patients with HHT are at an increased risk of brain abscesses if they develop _____ _____ of the lungs
AV fistulas (15-45% of patients)
Criteria for diagnosis of HHT (4) 3 of 4 required for diagnosis
- recurrent spontaneous epistaxis
- telangiectasia of the mucosa and skin
- AV malformation involving lungs, liver or CNS
- family history of HHT
What might you consider on your clinical differential in patients with multiple telangiectasias?
-how would you differentiate the two conditions?
Hereditary hemorrhagic telangiectasia VS CREST syndrome….anticentromere autoantibody testing +CREST -HHT
what monoclonal antibody is used in the treatment of HHT
bevacizumab: antibody against VEGF
What is the main clinical (dental) consideration for a pt with HHT?
antibiotic prophylaxis….HHT pt may have an AV fistula on the lung…. also 1% of HHT pts have a brain abscess
hypermobility of joints, easy bruising, elasticity of skin is characteristic of what disease?
Ehlers-Danlos syndrome (group of inherited CT disorders)
Most cases of ehlers-danlos are inherited ___ ___
autosomal dom
4 clinical types of ehlers-danlos syndrome
- classical
- hypermobility type
- vascular type
- Type 8
What type of scarring is characteristic of classical type ehlers-danlos
papyraceous healing- minor skin injury= skin that resembles crumpled cigarette paper
Defects in type 1 or V collagen leads to what type of ehlers-danlos
classical type
What collagen type is defective in vascular type ehlers danlos? What is the inheritance pattern of this type?
type 3….AD
Extensive bruising with everyday trauma, arterial bowel and uterine rupture and decreased life expectancy are characteristic of
vascular type ehlers danlos
What characteristic oral feature is present in type 8 ehlers-danlos syndrome
marked periodontal disease at an early age
50% of patients with ehlers danlos can touch the tip of the tongue to the tip of the nose, this is called ____ _____
Gorlin sign
Oral manifestations of ehlers danlos (4)
- Gorlin sign: 50% of patients can touch the tip of tongue to the tip of nose
- Easy bleeding of the oral mucosa on manipulation
- Tendency for recurrent subluxation of the TMJ
- Possibly increase in pulp stones in classical type Ehlers danlos
Characterized by intellectual disability, seizure disorders, and angiofibromas of the skin
Tuberous sclerosis
____ of cases of Tuberous sclerosis represent new mutations
66%
-rest inherited auto dom
Genetics for Tuberous sclerosis
- TSC1 chromo 9
- TSC2 chromo 16 more common and more severe
prevalence of Tuberous sclerosis
1:10,000
Facial angiofibromas predominantly occur where in tuberous sclerosis? What is the old name for these?
Nasolabial fold area predominantly…Adenoma sebaceum (neither adenomas nor sebaceous, so term discontinued)
Tuberous sclerosis: similar lesions to facial angiofibromas that are found in the nail area are called?
Ungual or periungual fibroma
Characteristic skin lesions of tuberous sclerosis (4)
facial angiofibromas
ungual fibromas
shagreen patches (conn tissue hamartoma)
ash-leaf spots (ovoid areas of hypopigmentation)
Whats the term for the connective tissue hamartomas on the skin of the trunk in tuberous sclerosis?
Shagreen patches (named because of their resemblance to sharkskin-derived shagreen cloth)
What are ovoid areas of hypopigmentation in tuberous sclerosis (5% of children without the syndrome can also have this)? What is used to visualize these?
ash-leaf spots..UV (wood’s lamp) light
CNS manifestations of tuberous sclerosis (4)
- seizure disorder
- intellectual disability
- tuberous hamartomas in the CNS (“potato like growths” seen on MRI or at autopsy)
- Subependymal giant cell astrocytoma of the brain (holy shit)
What is the cardiac lesion and the kidney lesion associated with tuberous sclerosis?
- cardiac rhabdomyoma
- kidney: angiomyolipoma
What are the 4 Oral manifestations of tuberous sclerosis?
- Enamel pitting of the facial anterior permanent dentition in 50-100%
- Multiple fibrous papules: 11-56%
- Diffuse fibrous gingival enlargement
- Radiolucencies in the jaws which are dense fibrous connective tissue proliferations
diagnosis of tuberous sclerosis requires 2 major or 1 major and 2 minor criteria. Major criteria include (9)
- Facial angiofibromas
- Ungual or periungual fibromas
- Hypomelanotic macules (3+)
- Shagreen patch
- CNS hamartomas
- Subependymal giant cell astrocytoma
- Cardiac rhabdomyoma
- Renal angiomyolipoma
- Multiple retinal nodular hamartomas
Minor criteria for tuberous sclerosis (5)
- Multiple enamel pits
- Gingival fibromas
- Bone “cysts” (fibrous proliferations)
- Multiple renal cysts
- Hamartomatous rectal polyps
Radiolucent bony lesions of tuberous sclerosis resemble what 2 histologic entities?
desmoplastic fibroma or central odontogenic fibroma
What are the 2 alternate names for Multiple hamartoma syndrome?
Cowden syndrome
PTEN hamartoma-tumor syndrome
Mutation in _____ gene on chromo 10 is characteristic of Cowden syndrome.
____ of people with the syndrome lack this mutation
PTEN(phosphatase and tensin homolog)
20%
Inheritance pattern and prevalence for multiple hamartoma syndrome
autosomal dominant
1:200,000
Multiple hamartoma syndrome has overlapping clinical features with what three syndromes? (They all have mutations of PTEN)
Lhermitte-Duclos disease
Bannayan-Riley-Ruvalcaba
Proteus-like syndrome
The multiple skin papules primarily of the face especially around the nose and ears seen in multiple hamartoma syndrome are most commonly what type? What age do these typically appear?
trichilemmomas
can also have: hemangiomas, neuromas, xanthomas, lipomas
Appear during the 2nd decade of life
Patients with cowden syndrome may have thyroid disease such as a _______…. They are also more prone to ______ of the breast
goiter or thyroid adenoma (also thyroid adenocarcinoma)
fibrocystic disease
Avg age of breast malignancy in cowden syndrome patients is ____
40
10 years younger than the avg
What are the 3 oral manifestations of multiple hamartoma syndrome?
- Multiple papules of the gingiva, tongue, buccal mucosa
- High arched palate
- Perio dz and caries
Oral papules of cowden syndrome are histologically
fibroepithelial hyperplasia
What are the 3 diagnostic criteria for multiple hamartoma syndrome? How many do you need to have to qualify for dx?
2+ of the following:
- Multiple facial trichilemmomas
- Multiple oral papules
- Acral keratoses
Peutz-Jaghers vs Gardner Syndrome: Which develops which type of polyp?
Peutz-Jaghers: Hamartomatous polyps in the jejunum and ileum, but patients are at 10-18x greater risk for general GI, breast, GU, and pancreatic caner VS Gardner Syndrome: adenomatous polyps (FAP from APC gene mutation) in COLON 100% turn to cancer
Peutz-Jaghers vs Cowden: What type of lesions and where? Also, both have increased risk for cancer, but differ on location - what is the location for each?
Both have hamartomatous lesions and have greater risk of cancer, but PJ = polyps in the SI and cancer in GI, Breast, GU and panc……Cowden = hamartomas of the skin (oral cavity), increase cancer risk in thyroid and breast
2 alternate names for Tuberous Sclerosis?
- Epiloia
2. Bourneville-Pringle syndrome
