Dermatology Genetics Flashcards
periungual fibromata (benign tumour composed of fibrous / connective tissue) (which in this case is periungual = “around the nail”) can be due to?
Trauma – if there is just one.
BUT if there are multiple –> person could have tuberous sclerosis.
what is tuberous sclerosis?
one of the most common genodermatoses.
It is a genetic disorder characterised by hamartomas in many organs. May have skin lesions, epileptic seizures, developmental delay. Severity varies widely.
May present as infantile seizures, earliest cutaneous sign is ash-leaf macule.
Autosomal dominant BUT new mutations are common.
what are ash-leaf macules and what is their significance?
they are depigmented macules which are found in 90% cases of tuberous sclerosis. Can be hard to spot in pale-skinned people - so can use a Wood’s lamp to spot it.
what tumours may be present in tuberous sclerosis?
periungual fibromas facial angiofibromas hamartomas bone cysts cortical tubers
what is a hamartoma?
an overgrowth of normal tissue - not malignant or benign
what are angiofibromas?
non cancerous tumours composed of fibrous tissue and blood vessels - they chiefly occur in nasal cavities and upper throat (but it is FACIAL angiofibromas which are likely to occur in tuberous sclerosis - these are pinky red spots in a butterfly distribution across the face).
aside from ash-leaf macules, what are 2 other skin signs of tuberous sclerosis?
shagreen patches (areas of thick, leathery skin which are dimpled like orange peel) enamel pitting in teeth
cortical tubers can be found in tuberous sclerosis. What is their significance?
they can cause epilepsy, and varying degrees of mental impairment
tuberous sclerosis is autosomal dominant/ recessive?
autosomal dominant (but new mutations are common). There are mutations in genes coding for tuberin and hamartin
why does an older father increase the chance of new mutations?
the older the father, the more mutations his sperm have been through
what does variable expressivity of genetic diseases mean?
means that disease severity can be variable
what does variable penetrance of genetic diseases mean?
means that individuals with the mutation may not show the disease
what is epidermolysis bullosa?
group of genetic skin fragility conditions, which could be dominant/ recessive/ new mutation/ acquired (as an autoimmune disease)
there is variable severity - some have blistering at birth, some present as adults.
Blistering at birth does NOT determine the prognosis
what are the 3 types of epidermolysis bullosa?
- SIMPLEX EB (the keratinocyte integrity is affected - so get fragile blisters)
- JUNCTIONAL EB (mutation is at the DEJ)
- DYSTROPHIC EB (mutation is at the dermis, so damage here induces scarring (like there would be in surgery of a 3rd degree burn)
sometimes in epidermolysis bullosa, the digits end up looking like a mitten. Why is this?
every time the hand is traumatised, it heals with a scar - the digits eventually are fused together and left like a mitten
what is the acquired form of EB?
it’s a rare autoimmune disease - usually presents in adult life, and tends to be localised to areas which are easily damaged e.g. hands, feet, buttocks
what is haploinsufficiency?
when a diploid organism has only a single functional copy of a gene (other copy is inactivated by a mutation) and so the single functional copy doesn’t produce enough gene product to bring about normality, and so causes an abnormal/ diseased state. (can be contrasted with haplosufficiency - where the single, unmutated allele can produce enough gene product to maintain the wild-type phenotype without the other allele)
what is a dominant negative disease mechanism?
when there is a mutated gene that acts antagonistically to the wild-type (normal) allele - causing the normal protein to stop working
what is a gain of function mutation?
when the mutant protein gains a new function - affecting cell processes
what is a complete loss of protein?
autosomal recessive - 2 faulty copies of gene produce NO protein
what are café au lait macules? what is their significance?
common birthmarks, presents as hyperpigmented skin patches with a sharp border. Usually present at birth/ appear in early infancy. Sun darkens them. More than 3 are uncommon, and more than 5 suggests genetic disease!!! café au lait macules have excessive numbers of melanosomes, produced by normal numbers of epidermal melanocytes.
what is neurofibromatosis type 1?
genetic disorder that affects the bone, soft tissue, skin, and nervous system. Characterised by:
- 6 or more café au lait macules
- multiple neurofibromas (tumours, on, or hanging off, the skin)
- freckling (under armpits, areas of skin folds)
- Lisch nodules (tiny tumours of the iris)
in atopic eczema, there is a mutation in the _____ gene?
filaggrin
in atopic eczema, the mutation in the filaggrin gene causes ichthyosis vulgaris. What is ichthyosis vulgaris?
ichthyosis vulgaris is excessive, dry scaly skin. It’s the most common of the inherited ichthyoses (which are skin disorders characterised by rough, scaly skin). Ichthyosis vulgaris results from loss-of-function mutations in the gene encoding filaggrin. Atopic eczema is present in 50% people with ichthyosis vulgaris
what is the significance of filaggrin?
filaggrin is required for the binding of keratin fibres in epidermal cells - to form an effective skin barrier. Xerosis (dry skin) results from reduced skin hydration associated with defective filaggrin.
