Metabolic Diseases & Syndromes

Question 1

Paget’s Disease

Answer 1

• Mutation of SQSTM1 gene
  
  • ​SQSTM1 gene provides instructions for making protein p62, which helps in regulating formation of osteoclasts
• Abnormal resorption & deposition of bone
  
  • Bone broken down and replaced much faster than normal
  • New bone is weaker and less organized than normal bone
• Distortion and weakening
• Unknown cause
• Inflammatory, genetic, and endocrine factors may play a role
• Characterized by abnormal & dysfunctional resorption & deposition of bone = weakening and deformation of bone
• Bowing of legs
• Enlargement of jaws
• Involves multiple areas of the skeleton
• Results in enlargement of skull, jaws, facial bones and deformity of spine & long bones
• Increased pathologic fracture
• Occurs in pts >40yo
  
  • Always >40yo
• More common w/ increasing age
• Gradual onset & chronic course
• Old white guys classically
• Narrowing of skull foramina leads to cranial nerve dysfunction
• Enlargement of jaws and widening of alveolar ridges
  
  • Dentures don’t fit
  • Spaces between teeth
• When jaws are involved, skull is also involved
• Enlarged cranium and bony deformity = stooped posture and bowing of legs
• Osteoporosis circumscripta: Large circumscribed areas of RL seen in early stages of disease

Question 2

Pagets Disease: Rad

Answer 2

• Early stages show decreased bone density
• Later stages, patchy, poorly-defined RO areas (“cotton wool”)
  
  • During osteoblastic phase, patchy areas of sclerotic bone are formed which tend to become confluent
  • Happens everywhere and not focal
  • Different from fibrous dysplasia, which can be monostotic, always expansion, always under 20yo
  • In all 4 quadrants and no expansion; always over 40yo
• Increased thickness of diploe of skill
• Multiple teeth w/ hypercementosis
• Lincoln’s Sign or Blackbeard: Uptake condyle to condyle

Question 3

Pagets Disease: Tx

Answer 3

• Chronic, slowly progressive, seldom causes of death of pt
• Can cause bone pain, bone deformity, neurologic problems
• Calcitonin and bisphosphonates inhibit osteoclastic resorption
• Not usually fatal, but has complications
• Increased incidence of osteosarcoma

Question 4

Pagets Disease: Lab values

Answer 4

• ↑serum alkaline phosphatase
• Normal blood Ca2+
• Normal blood phosphorus
• ↑urine hydroxyproline levels

Question 5

Hyperparathyroidism

Answer 5

• Primary: Parathyroid gland hyperplasia, adenoma, carcinoma → increased PTH production
  
  • Cause is from the gland itself and the main reason is because of an adenoma on one of the 4 parathyroid glands
• Secondary: Kidney disease → Hypocalcemia → increased PTH production
  
  • Not a problem w/ the gland itself
  • Results from compensatory increase in the output of PTH in response to hypocalcemia either from kidney disease or decreased Vitamin D absorption due to diet
• Hypercalcemia leads to:
  
  • Bone & joint pain
  • Renal calculi
  • Peptic ulcers
  • Cognitive impairment
  • Painful bones, renal stones, abdominal groans, psychotic moans

Question 6

Hyparathyroidism: Rad

Answer 6

• Generalized decrease in bone density → osteoporotic “ground glass” or “salt and pepper” appearance due to loss of trabeculation & lamina dura
• Loss of trabeculation, lamina dura, cortical plates
• Occasionally, giant cell tumors of bone (“brown tumors”)
• NO expansion, no displacement of teeth, not focal → can’t be fibrous dysplasia

Question 7

Hyperparathyroidism: Lab Features

Answer 7

• Primary: Increased serum Ca2+ (>12.5mg%) and PTH
• Secondary: Decreased or normal serum Ca2+; increased PTH

Question 8

Hyperparathyroidism: Microscopic

Answer 8

• Increased bone turnover
• Giant cell lesions identical to CGCG
• Osteoclastic resorption in hyperparathyroidism
• New bone formation in hyperparathyroidism

Question 9

Hyperparathyroidism: Tx

Answer 9

• Primary: Excision of parathyroid gland(s)
• Secondary: Renal dialysis or renal transplant

Question 10

Osteogenesis Imperfecta

Answer 10

• Group of genetic disorders w/ impaired collagen maturation
• COL1A1 OR COL1A2​ mutations
• Defective cross-linking of collagen
• Osteoblasts produce defective osteoid
• Bones are brittle or fragile
• Congenital onset is more severe: Multiple fractures in utero; often die at birth or shortly after
• Later onset is milder: Normal lifespan
• Hallmark: Bone fragility
• Skeletal features:
  
  • Multiple fractures: Sometimes bony deformity
  • Radiographic: Thin cortical plates, multiple fractures, excessive callus formation
  • Large skull w/ prominent facial bones
  • Kyphosis and/or scoliosis
  • Hyperextensible joints
  • Thin cortical plates
• Eyes: Blue sclera
• Ears: Hearing loss
• Ligament laxity - bowing/deformity of long bones
• Increased prevalence of Class III malocclusion due to MX hypoplasia w/ or w/o MN hyperplasia
• Opalescent teeth: Diffuse blue-brown discoloration; slight translucence

Question 11

Osteogenesis Imperfecta: Tx

Answer 11

• No tx or cure
• Px varies from death at birth to normal lifespan
• # of bony fractures decreases w/ age

Question 12

Osoteopetrosis

Answer 12

• Osteoclasts are unable to resorb bone
• Marked thickening of bone density bc osteoclasts don’t stop laying down bone
• Defect in bone remodeling
• Increased density of bone (skull, jaws) and osteomyelitis
• Generalized hyperdensity of MX and MN w/ multiple malformed and impacted teeth

Question 13

Ectodermal Hyperplasia

Answer 13

• 2 Major types
  
  • Anhidrotic: Partial or complete absence of eccrine sweat glands, sebaceous glands, hair follicles
  • Hidrotic
• Facial abnormalities
  
  • Prominent frontal bone
  • Midface hypoplasia and saddle nose
• Skin & appendages
  
  • Fine, sparse hair
  • Scanty eyelashes & eyebrows
  • Decreased eccrine sweat glands → decreased sweating → heat intolerance and fever
  • Dry skin
  • Hypoplastic or aplastic nails
• Oral manifestations
  
  • Hypodontia or anodontia of primary and permanent dentitions
  • Hypoplasia of alveolar ridges
  • Decreased vertical dimension
  • Protuberant lips
  • Cone-shaped teeth
  • Unerupted teeth
  • Xerostomia

Question 14

Ectodermal Dysplasia: Tx

Answer 14

• Cool envt
• Lube for dry skin
• Dental prostheses
  
  • Bone grafting & implants
  • Dentures
• Normal lifespan

Question 15

Cherubism

Answer 15

• Mutation of SH3BP2 gene
  
  • Controls osteoclasts & osteoblasts
• Autosomal dominant, genetic disease
• Clinical features usually appear by 10yo
  
  • Progressive, non-tender swelling of jaws
  • MN almost always involved
  • Swelling → Round “cherubic” face
  • Stops growing at some point
  • Eyes tilted up
• Progressive, nontender swelling of jaws
• MN almost always involved
• Radiographic features
  
  • Bilateral RL features → expansion & sometimes perforation of cortices
  • Multilocular RL areas
  • Multiple unerupted teeth are displaced by lesions
• Premature exfoliation of primary teeth and unerupted permanent teeth
• Not true hypodontia bc teeth haven’t fully developed
• Bilateral, multilocular, expansile RL lesions
• Giant cells like hyperparathyroidism and CGCG

Question 16

Cherubism: Tx

Answer 16

• Lesions stabilize at puberty
• Difficult to surgically remove lesions
• Surgical recontouring can be done for esthetics

Question 17

Gardner Syndrome

Answer 17

• AKA Familial Adenomatous Polyposis
• Rare disorder inherited as AD trait
  
  • Genetic
  • Mutation of APC gene
• Characterized by familial colorectal poplyposis
• Other GI abnormalities
• Skin, ST, retina, skeletal system, teeth
• Important syndrome bc
  
  • 3/4 of pts have dental abnormalities or osteomas
  • Associated w/ cancer
• Polyps (adenomas) of colon and rectum
  
  • Almost all pts w/ polyps develop carcinoma of colon/rectum
• Benign and very RO
• Gardner Syndrome: Can have intestinal carcinoma
• Peutz-Jeghers Syndrome: Polyps have low malignant potential
• Multiple osteomas of bone
  
  • Osteoma is a benign neoplasm of bone
  • Often precede intestinal polyps
  • Found mainly in calvarium and facial skeleton
• Multiple epidermal cysts & fibrous tumors of skin
• Multiple unerupted permanent and supernumerary teeth
• Colonic polyps develop during 2nd decade of life
  
  • Characterized by familial colorectal polyposis
• Osteoma of MN
• Bilateral MN osteomas & unerupted teeth

Question 18

Gardner Syndrome: Tx

Answer 18

• Pts w/o polyps should be periodically reevaluated
• Once polyps develop, colectomy is done prophylactically before they develop into cancer
• Px depends on intestinal carcinoma
• Major problem is high risk of malignant transformation of polyps
  
  • By 30yo, 50% of pts have colorectal carcinoma
  • By 60yo, rates approach 100%
• Osteomas & epidermoid cysts removed
• Prophylactic colectomy rec’d

Question 19

Other name for Gardner Syndrome

Answer 19

Familial Adenomatous Polyposis

Question 20

Other name for Craniofacial Dysostosis

Answer 20

Crouzon Disease

Question 21

Craniofacial Dysostosis

Answer 21

• Crouzon Disease
• Genetic disease
• Manifestations are due to synostosis = early closure of sutures
• Associated w/ increased paternal age
• Mutation w/ FGFR2 gene
• Midface hypoplasia & exophthalmos
• Craniofacial
  
  • Midface hypoplasia
  • Prominent nose
• Brain is pushing on eyes & skull
• Class III occlusion bc jaw growing normally but skull isn’t
• Eyes
  
  • Exophthalmos
  • Divergent strabismus
  • Increased interpupillary distance
  • Optic nerve damage and possible blindness
• Brain increases in size, but skull doesn’t grow
• Brain puts pressure on inner layer of skull
• Leads to “beaten metal” or “beaten copper” skull appearance on rads
• Oral
  
  • High-arched palate, sometimes cleft
  • Hypoplastic MX → malocclusion
• Apert Syndrome: Craniofacial dysostosis w/ webbing b/w adjacent fingers and toes (syndactyly)

Question 22

Craniofacial Dysostosis: Tx

Answer 22

• Craniectomy early in life to provide space for brain
• Ortho & orthognathic surgery
• Complications: Impaired hearing, speech, vision; mental retardation
• May have normal lifespan

Question 23

Cleidocranial Dysplasia

Answer 23

• Defect in the CBFA1 (RUNX2) gene
  
  • Guides osteoblastic differentiation
• Genetic disease
• Skull
  
  • Fontanels are open or have late closure
    
    • Disrupted growth of skull and clavicles
  • Sutures remain open → wormian bones
    
    • Little bones form in the spaces
  • Brachycephalic skull
  • Prominent frontal, parietal and occipital bones
• Normally clavicles hyperplastic
  
  • 10% have clavicle absence
  • Narrow and drooping shoulders
  • Unusual motility of shoulders
• Shoulder girdle
  
  • Aplasia, hypoplasia, or thinning of clavicles
  • Hypermobility of shoulders
• Oral
  
  • High narrow palate
    
    • May be cleft
  • Hypoplastic MX and sinuses
• Teeth
  
  • Prolonged retention of primary teeth
  • Succedaneous teeth may fail to erupt or have delayed eruption due to lack of cellular cementum
  • Multiple unerupted supernumerary teeth
  • Severe malocclusion

Question 24

Cleidocranial Dysplasia: Tx

Answer 24

• Orthognathic surgery and orthodontics
• Lifespan is normal

Question 25

Other name for Mandibulofacial Dysostosis

Answer 25

Treacher Collins Syndrome

Question 26

Mandibulofacial Dysostosis

Answer 26

• Genetic disease
  
  • Mutation in TCOF1 gene
  • Defects of structure derived from 1st and 2nd branchial arches
• Face: Convex facial profile
  
  • Downward sloping palpebral fissures
  • Hypoplasia of MN and malar bones
  • Large mouth
  • Missing ear canals and zygomatic bones
  • Hypoplastic zygomatic arch
  • Underdeveloped condyle & ramus
  • Deepened antegonial notch
  • MN hypoplasia & retrognathia
• Condyle messed up so MN doesn’t grow properly
• Eyes
  
  • Fissure (coloboma) of lower eyelid
  • Deficiency of eyelashes
• Ears
  
  • Deformed pinna
  • Conductive hearing loss
• Face: Convex profile
  
  • Downward sloping palpebral fissures
  • Hypoplasia of MN and malar b ones
  • Large mouth
• Oral
  
  • Hypoplastic MN
  • High palate, sometimes cleft
  • Malocclusion

Question 27

Mandibulofacial Dysoastosis: Tx

Answer 27

• Surgery for eyes and ears
• Orthognathic surgery and ortho
• Normal lifespan

Question 28

Neurofibromatosis (von Recklinghausen’s Disease of skin)

Answer 28

• Multiple neurofibromas
  
  • Well circumscribed, exophytic
  • Diffuse involving deep tissues
• “Café au lait” spots
  
  • Melanotic macules >1.5cm
  • Freckles in axilla
• Oral lesions
  
  • Oral neurofibromas in 7-20% of pts
  • Neurofibromas may be well circumscribed or diffuse
  • Macroglossia
• ST sarcomas: Occur in <10% of pts
• Bony lesions
• CNS lesions

Question 29

Neurofibromatosis (von Recklinghausen’s Disease of the Skin): Tx

Answer 29

• Not possible to surgically remove all neurofibromas
• Cosmetic problems
• Sarcomas have a poor px

Question 30

Papillon-Lefevre Syndrome

Answer 30

• AKA Juvenile Periodontitis w/ Palmar-Plantar
• Hyperkeratosis
• Juvenile periodontitis
  
  • Severe alveolar bone loss of primary and permanent dentitions
  • Gingivitis and deep pockets
  • Premature loss of teeth
• Hyperkeratotis of palms and soles

Question 31

Other name for Papillon-Lefevre Syndrome

Answer 31

Juvenile Periodontitis w/ Palmar-Plantar