6.2 Inherited disorders in dentistry Flashcards
What are the 3 broad categories of hereditary disorders of tooth structure?
- Amelogenesis imperfecta
- Dentinogenesis imperfecta (I, II, III)
- Dentine dysplasia (I, II)
Describe amelogenesis imperfecta.
- Can be autosomal dominant/recessive or X-linked
- Enamel proteins affected e.g. enamelin and amelogenin
- Teeth have an abnormal appearance, yellow/brown/grey in colour
- Higher risk of caries and dentine sensitivity
- Doesn’t usually have wider manifestations as most proteins are specific to enamel
Describe dentinogenesis imperfecta.
- Autosomal dominant
- 3 types
- Dentine is usually not the only structure involved, wider bodily manifestations common
Describe DI type I.
- Caused by mutations in COL1A1 or COL1A2
- DI type I is a part of osteogenesis imperfecta
- Osteoporosis
- Frequent fractures
- Deafness
- Blue sclera
- Short stature
- Teeth appear translucent and show signficant attrition
Describe DI type II.
- Caused by dentine sialophosphoprotein mutations
- Typically isolated to teeth only, some may have deafness
- Teeth are blue-gray or amber brown and opalescent
- Bulbous crowns, narrow roots, small pulp chamber
- Enamel shears away
- Deciduous dentition more severely affected
Describe DI type III.
Found in a population living in Maryland, USA.
Thin dentine, large pulpchamber- “shell teeth”- caused by mutation in dentine sialophosphoprotein.
Describe dentine dysplasia.
Problem with growth/morphology of denitne, something has gone wrong during development.
Autosomal dominant.
Describe dentine dysplasia type I.
- Normal appearance of crown
- Short, blunt and conical roots leading to premature tooth loss
- Pulp chambers and root canals are obliterated in deciduous teeth, and crescent shaped in permanent teeth
Also called radicular dentine dysplasia.
Describe dentine dysplasia type II.
- Caused by DSPP mutations
- Deciduous teeth: brown/blue discolouration, pulp chamber obliteration
- Permanent teeth: normal colour, large thistle shaped pulp chamber, pulp stones may be found
Also called coronal dentine dysplasia.
What are the 2 types of hypodontia?
Non-syndromic: isolated hypodontia, most common, can be familial.
Syndromic: ectodermal dysplasia, Incontinentia Pigmenti,Down’s syndrome, Ellis-van Crevald
Describe Incontinentia Pigmenti.
- X-linked dominant disorder
- NEMO gene
- Affected males die in utero
- Affected females experience hypodontia, conical teeth, retinal detachment, vesicles/blistering rash, swirling hyper-pigmentation, alopecia, dystrophic nails
What is HHT?
- Hereditary haemorrhagic telangiectasia
- Abnormal connections between arteries and veins
- Occur preferentially around the mucocutaneous junction e.g. around lips
- Experience regular nosebleeds
- Can also have arterio-venous malformation of other viscera including brain and lungs- potentially lethal
What is Lesch-Nyhan syndrome?
- X-linked recessive metabolic condition
- Deficiency of HGPRT enzyme
- Error in purine metabolism, causes extremely high levels of uric acid
- Leads to basal ganglia damage, severe intellectual disability, bite at their lips and fingertips etc therefore causing perioral manifestation
- Special oral appliances have been proven to reduce risk of self injury
Cleft lip and palate can be non-syndromic or syndromic, name some associated syndromes.
- Van der Woude
- Velocardiofacial sydrome
- Stickler syndrome
- Treacher Collins
Describe Van der Woude syndrome.
- Autosomal dominant
- IRF6 mutations
- Characteristic lip pits (small salivary glands)
Describe velocardiofacial syndrome.
- Autosomal dominant
- Abnormal pharyngeal arch development meaning many structures are affected e.g. heart, thymus, palate, stature
- Associated with cleft palate
Describe Stickler syndrome.
- Autosomal dominant condition, COL2A1 and COL11A1 muations
- Skeletal dysplasia
- Distinct U-shaped palate
- Flat nasal bridge and face
- Prominent eyes
- Cleft palate and bifid uvula
Describe Treacher Collins syndrome.
- Autosomal dominant
- Extremely small mandible
- Cleft palate
- Dysplastic ears, deafness
What is pharmacogenetics?
Study of how genes affect an indiviudal’s drug response.
Give examples of pharmacogenetic responses.
Malignant hyperpyrexia susceptibility: life-threatening reaction to volatile anaesthetic gases e.g. halothane. Such anaesthetics rarely used nowadays. Rare.
Abacavir hypersensitivity: severe reaction to Abacavir (HIV drug), approx. 5-7% of people affected.
What are the top 4 cancer predisposing disorders?
- Peutz-Jeghers’ Syndrome (AD)
- Familial Adenomatous Polyposis (AD)
- Cowden Syndrome (AD)
- Gorlin Syndrome (AD)
Describe Familial Adenomatous Polyposis.
- Affects approx. 1 in 8000
- APC gene affected
- Develop hundred to thousands of colorectal adenomatous polyps
- Susceptibility to upper GI and other cancers, and desmoid tumours
- Many oral symptoms: epidermoid cysts, osteomas (bony lumps on forehead or face), odontomas (benign teeth containing tumours in the jaw)
- Hypodontia, supernumerary teeth, impacted teeth, jaw cysts
Describe Peutz-Jeghers’ syndrome.
- Causes polyps in the bowel
- Uncommon
- Pigmented macules of skin and mucous membranes
- Predisposed to GI-tract cancers and extra-intestinal neoplasms (ovary, cervix, breast, testes, pancreas)
Describe Cowden syndrome.
- Uncommon
- Multiple benign hamartomas
- Many small lumps and bumps on skin
- Lumps on gingiva
- Pebble stone tongue
Describe Gorlin-Goltz syndrome.
- Also called nevoid basal cell carcinoma syndrome
- Multiple basal cell carcinomas on the skin
- Young onset
- Intracranial calcification and skeletal abnormalities
- Multiple odontoegnic keratocysts
Common dental disease is multifactorial, involves a combination of polygenic contribution and environmental factors, name some genes believed to be involved in caries and periodontal disease.
Caries:
- Ameloblastin (AMBN)
- Amelogenin (AMELX)
- Enamelin (ENAM)
- MMP-16
- Mucin 5 (MUC5B)
Periodontal disease:
- IL-1, IL-6, IL-8, 1L-10, IL-37
- MMP-3/8/9
- VDR
