Genetics Flashcards
what is tuberose sclerosis?
a rare multi-system genetic disease that causes benign tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin. one of the most common genodermatoses.
what might tuberose sclerosis present as in infants?
infantile seizures
what is the earliest cutaneous sign?
ash-leaf macules
what type of mutation is tuberose sclerosis?
autosomal dominant but new mutations are common
what do ash-leaf macules look like?
depigmented macules
what can be used to make ash-leaf macules more visible?
a wood’s lamp
what tumours are found in tuberose sclerosis?
periungual fibromas
facial angiofibromas cortical tubers &/or calcification of falx cerebri
hamartomas (angiomyolipomas)
bone cysts
when do angiofibromas start to develop in tuberose sclerosis?
in the first few years of life
what other skin signs are present in tuberose sclerosis?
shagreen patches
enamel pitting
what can cortical tubers cause in tuberose sclerosis?
epilepsy & varying degrees of mental impairment
what do the affected genes code for in tuberose sclerosis?
tuberin & hamartin
what is epidermolysis bullosa (EB)?
a group of genetic skin fragility conditions of varying severity
what type of mutations are present in EB?
can be dominant, recessive, new mutations or acquired
what does simplex EB affect?
affects keratinocytes binding together, blisters at sites of trauma
what does junctional EB affect?
affects proteins in DEJ
what does dystrophic EB affect?
affects the dermis and the organisation of the proteins within it, skin is progressively shed and replaced by more and more scarring
how many genes are involved in EB & what do they affect?
10
skin structure & adhesion
what is EB aquisita?
a rare autoimmune condition, acquired usually in their 6th/7th decade of life
what happens in haploinsufficiency?
only one copy of the gene is working - reduced protein production
what happens in dominant negative mutations?
expression of an abnormal protein interferes with normal protein
what happens in gain of function mutations?
mutant protein gains a new function, affecting cell processes
what happens in complete loss of protein?
autosomal recessive - need 2 faulty copies of the gene to stop production of a protein
when do cafe au lait macules occur?
from birth onwards
how many cafe au lait macules suggest a genetic disease?
more than 5
what are the two main clinical signs in neurofibromatosis type 1?
cafe au lait macules
neurofibromas
what are neurofibromas?
soft neural tumours
what other features are found in NF type 1?
plexiform neuroma - diffuse axillary/inguinal freckling optic gliomas 2 or morelisch nodules in the eye a distinctive bony lesion
when would lish nodules appear in the eye in NF 1?
aged 10+
what is the primary abnormality in atopic eczema & what is it determined by?
issue with skin’s barrier function
determined by genetic factors
which gene is important in skin barrier function?
filaggrin gene
what do filaggrin mutations cause?
ichthyosis vulgaris
what triad of symptoms describes eczema?
fine scaling (dryness of the skin)
keratosis pylorus
hyper-linearity
which layer of the skin is not present in ichthyosis vulgaris?
no granular layer
