Genoderm Flashcards
1
Q
Epidermolytic ichthyosis - genes
A
KRT1
KRT10 - no hands
2
Q
Ichthyosis vulgaris - gene
A
FLG/ profillagrin
Semi autosomal dominant
3
Q
Steroid sulfurase deficiency - gene
A
X linked recessive
STS gene deletion of Xp22.31
4
Q
Gene associated with pilomatricoma and carcinoma
A
CTNNB1
5
Q
Langerhanscell histiocytosis gene
A
BRAFV600E
6
Q
Diagnostic criteria for NF1
A
CANFOOL Cafe au lait macules - >6, >5 mm pre-pubertal or >15 mm post Axillary freckling Neurofibromas - X2 any, X 1 plexiform First degree relative Osseus lesions Optic gliomas Lischn nodules
7
Q
Epidermal naevus epidemiology
A
1 in 1000 infants
8
Q
Epidermal naevus clinical features
A
- 80% occur within first year of life
- Most commonly single linear
- Well circumscribed, hyperpigmented papillomatous papules or plaques
- Asymptomatic
- Rarely - hypopigmented
- Can thicken and become more verrucous - particularly over joints
Rarely - malignant change, if so will be post-puberty - Location: commonly trunk and neck, follows lines of Blaschko
- Naevus verrucosus: warty appearance
- Naevus unius lateris: extensive, unilateral plaques, often involving the trunk
- Ichthyosis hystrix: extensive bilateral involvement, also on the trunk
- Epidermal naevus syndrome: epidermal naevi with other anomalies - CNS, MSK
9
Q
Epidermal naevus pathogenesis (genes and what is it)
A
- Thought to originate from pluripotent cells in the basal layer of the embryonic epidermis, harmatomous process involves epidermis and at least some of papillary dwermis
- Possible mutations:
- Mutations identified in some: KRT1, KRT10, ATP2A2
- Common: FGFR3 mosaicism for activating mutations
- Have also found PIK3CA mutation
- RAS mutations have been observed in patients with keratinocytic epidermal naevi (HRAS>NRAS>KRAS)
10
Q
Epidermal naevus histology
A
- epidermal hyperplasia
- hyperkeratosis
- acanthosis
- papillomatosis
- variable parakeratosis
- focal acantholytic dyskeratosis
11
Q
Ddx epidermal naevus
A
- Naevus sebaceous
- Organoid naevi
- Lichen striatus
- Linear and whorled naevoid hypermelanosis
- Porokeratotic eccrine ostial and dermal duct naevus
- Linear LP
- X-linked dominant chondrodysplasia punctata
12
Q
Treatment epidermal naevus
A
- Full thickness excision: recurrence is common, and can be complicated by scarring
- Topical therapies with limited benefit: steroids, retinoic acid, tars, anthralin, 5-FU, podophyllin
- Systemic therapy: retinoids –> decreases thickness
- Laser ablation –> however to be effective must induce scarring
13
Q
PWS/Sturge Weber mode of inheritance and gene
A
GNAQ –> Q class G protein alpha subunits
Mosaic, with somatic mutations in lesional skin
Activating mutation
14
Q
PWS/Phakomatosis pigmentovascularis type 2 or overgrwoth of an extremity
A
GNA11 –> Q class G protein alpha sub units
Mosaic, with somatic mutations in lesional skin
Activating mutation
15
Q
Ataxia telangiectasia genetics
A
ATM gene - ATM protein is similar to phosphoinositol 3 kinase - regulates cell cycle, DNA repair, p53
Autosomal recessive
Loss of function
16
Q
Capillary malformation-AVM genetics
A
RASA1 and EPHB4
loss of function - p120-Ras-GAP protein and EPH receptor B4 in endothelial cells - interact and modulate MAPK signaling growth factor receptors
Autosomal dominant
17
Q
Cutaneous and mucosal venous malformations and Blue rubber bleb naevus syndrome genetics
A
TEK
Gain of function of TIE-2 - an endothelial cell-specific tyrosine kinase receptor that binds angiopoietins
Auutosomal dominant
Blue rubber bleb is mosaic
18
Q
Venous malformations genetics
A
TEK, PIK3CA
Gain of function of TIE-2 –> binds angiopoietins
PIK3CA - activates the AKT/mTOR pathway
19
Q
Lymphatic malformations genetics
A
PIK3CA - gain of function
TIE2 –> binds angiopoietins
PIK3CA activates the AKT/mTOR pathway
Mosaic, with somatic mutations in lesional tissue
20
Q
Hereditary lymphoedema genetics
A
GJC2
Loss of function: connexin 47 in gap junctions of lymphatic vessels
autosomal dominant
21
Q
CADASIL genetics
A
NOTCH3
Accumulation of NOTCH-3 protein in vascular smooth muscle cells
22
Q
Phakomatosis pigmentovascularis 1
A
Epidermal naevus + port wine stain
<5% of PPV cases
23
Q
Phakomatosis pigmentovascularis 2
A
Mongolian spots + PWS
75% of PPV cases
Other associations: naevus anaemicus, hypotrichosis, lipohypoplasia, hypoplastic nails
24
Q
Phakomatosis pigmentovascularis 3
A
Naevus spilus + naevus roseus
Other: naevus anaemicus, lymphoedema, hypotrichosis
25
Phakomatosis pigmentovascularis 4
CALM + capillary malformation
| Other: naevus anaemicus, naevoid hyper or hypopigmentation, naevus sebaceous
26
Phakomatosis pigmentovascularis 5
Dermal melanocytosis + cutis marmorata telangiectatica congenita
27
Sjogren larsson epi
- Autosomal recessive
- Prevalence <1 in 100 000
- Most common in northern Sweden
28
Sjogren larsson genetics and path
- Deficiency of microsomal fatty aldehyde dehydrogenase enzyme
- Mutations in ALDH3A2
- results in membrane alterations due to accumulation of fatty alcohol or fatty aldehyde modified lipids and proteins
- retarded myelination and variable degree of dysmyelination in periventricular white matter
29
Sjogren larsson clinical
- Cutaneous:
- Birth: erythema, hyperkeratosis, scaling. Rarely colloidon.
- Hyperkeratosis then becomes darker
- Ichthyosis varies from fine, white scales to larger, plate-like scales
- Prediliction: lower abdomen, neck and flexural areas
- Palmoplantar keratoderma - 70% patients
- Lichenification of flexural areas
- Extra-cutaneous:
- Ophthal: perifoveal glistening white dots in the ocular fundus - juvenile macular dystrophy
- CNS: delayed motor development, abnormal gait, pyramidal signs, spasticity, contractures. Seizures in 40%. MRI: white matter disease
30
Sjogren larrson diagnosis
- Histopath: orthokeratotic hyperkeratosis, papillomatosis and moderate acanthosis, well-developed granular layer
- Cultured skin fibroblasts/keratinocytes/leukocytes have reduced or absent FALDH activity
- SLS in detection of elevated free fatty alcohol in cultured fibroblasts and plasma also helpful
- Preferred method of diagnosis is DNA based molecular testing
- Can do pre-natal molecular diagnosis from CVS or amniocentesis
31
Refsum epidemiology and path
- Super rare
- Autosomal recessive - PAHX gene on 10p, and PEX7 on 6q
- M=F
- Deficiency in phytanoyl-CoA hydroxylase --> accumulation of phytanic acid in the serum
32
Refsum clinical
- Cutaneous: mild ichthyosis, begins after neurological symptoms
- CNS: ataxia, progressive peripheral polyneuropathy
- Eyes: retinitis pigmentosa with salt and pepper pigment
- ENT: deafness
- Arrhythmias, cardiac failure
33
Refsum diagnosis
- Cultured fibroblasts: increased serum phytanic acid
| - DNA mutational analysis if mutation known
34
Refsum management
- Dietary restriction of phytanic acid - decrease green vegetables, dairy products and ruminant fats
- Plasma exchange removal of phytanic acid
- If diet and exchange instituted early on, progression of disease can be halted
35
Nail patella syndrome genetic mutation
LMX1B, AD
Aplastic or hypoplastic nails and patella, and renal issues - 40% nephropathy, 8% renal insufficiency
Iliac horns on pelvic x-ray
triangle shaped lunula
36
Goltz mutation and epi
PORCN ++ females
37
Goltz clinical
1. Cutaneous: worm like atrophoderma, fat herniation, raspberry papillomas
2. Other ectodermal: nail dystrophy, sparse hair, dentition (hypodontia)
3. Eyes: unilateral, microphthalmia etc
4. Bone: 80% limb abnormalities
5. Dysmorphic facies - pointed chin, large malformed ears, etc
38
Dyskeratosis congenita main features and pathogenesis
Telomere shortening
DYC 1 + other mutations
1. Reticulate hyperpigmentation - generalized
2. Oral leukoplakia
3. Nail dystrophy - pterygium
4. BM failure
5. Incr risk malignancy: SCC, AML, GI malignancy
6. Other: liver cirrhosis, lung fibrosis, cryptorchidism, hypogonadism, incr risk infections, short stature, developmental delay
39
Dowling Degos clinical and pathogenesis
```
KRT5 mutation, M>F, AD
Clin:
onset 30s-40s - flexural reticulate hyperpigmentation
open comedones
cysts
acne
HS
assoc: HS, SCCs, KAs, nail dystrophy, seb ks, cysts
```
40
Chediak Higashi main clinical features
```
NUPBOIL
Neuro - DD, etc
Ulcerations - PG, oral ulceratio, etc
Pigment - bronze colour
Bleeding - bruises, ecchymoses
Ocular - nyastagmus, strabismus, no change in visual acuity
Infections - skin, resp
Lymphoproliferative - HLH sx, and also LYST gene mutation
```
41
Chronic granulomatous disease main features
M>F 90%
Reduced NADPH
Clinical:
1. Cutaneous: staph infections, sterile cutaneous, lupus like piccture
2. Extra-cutaneous: lymphadenitis, granulomas elsewhere - GIT - looks like IBD, can basically be anywhere
42
Omenn syndrome/SCID main features
Defective cell and humoral immunity
X linked
Omenn: RAG1 and RAG2 mutation
SCID - ADA important one (associated with DFSP)
Clinical:
1. Cutaneous: maternofoetal GVHD - seb derm, morbilliform, then eczema, erythroderma, alopecia. ADA linked with DFSP - multiple in 10s-20s
2. Chronic diarrhoea, failure to thrive, HSM, LN, recurrent infections
Need to diagnose early before give blood products etc
Rx: IVIG, HSCT, ADA replacement
43
Wiskott Aldrich Syndrome main features
```
WASP mutation
X linked - boys
Clinical - TIME
Thrombocytopaenia - bleeding
Infections - cutaneous, resp tract, CNS, etc
Malignancy - lymphoma
Eczema
```
44
Hermansky Pudlak main features
BLOC 1/2/3 mutation
```
Pigmentary dilution
Ulcers – knife cut ulcers and granulomas intertriginous
Decreased vision
Lungs - pul fibrosis
AR
K vitamin K not working à bleeder
```
45
Rothmund thompson gene and features
```
RECQL4 mutation
THOMPSON:
- Teeth abnormalities
- Ocular: cataracts
- Microcephaly
- Photosensitivity, poikiloderma, perforating
- Short
- Osteosarcoma + other cancers
- No hair
```
46
Ddx for photosensitive genodermatoses
```
XP
Rothmund Thompson
Bloom Sx
Cockayne Sx
Trichothiodystrophy
```
47
Cockayne sx gene and features
- Autosomal recessive
- defective transcription coupled NER --> inability to recover mRNA synthesis after exposure to UVR
- 2/3 have mutation in ERCC6, 1/3 in ERCC8
- Don't get skin cancers --> cells with low level damage are eliminated
Clinical
- Cutaneous:
- Photosensitivity, pigmented macules
- Loss of subcutaneous fat
- No increased risk of malignancy
- Alopecia
- Premature ageing
- Hypohidrosis
- Acral oedema
- Stellate scars
- Cold extremities
- CNS:
- Basal ganglia calcification
- Sensorineural hearing loss
- Intention tremor
- Ocular
- Pigmentary retinal degeneration - 'salt and pepper'
- Cataracts
- Nyastagmus and strabismus
- Dysmorphic facies
- Sunken eyes due to loss of adipose tissue
- Progeria
- Beaked nose
- Ortho
- Stooped posture
- Cachetic dwarfism
- Joint contractures
48
Bloom syndrome gene and features
```
BLM mutation
BLOOM:
- Butterfly rash
- Leukaemias, lymphomas and carcinomas
- Oral: lower lip blistering
- Otic and pulmonary infections
- Macules: cafe aut lait macules
```
49
Goltz syndrome gene and features
X linked, females only, PORCN
1. Linear dermal atrophy, fat herniations, raspberry like papillomas
2. 80% limb problems - skeletal
3. Ocular
4. Nail
5. Hair
6. Dysmorphic face
50
EN syndrome
FGFR/PIK3CA/AKT1 mutation or RAS/MAPK mutation
Cutaneous: EN, seb naevus, dyspigmentation, CALM, aplasia cutis congenita
CNS: hemimegalencephaly, seizures, DD
Ocular: coloboma, lipodermoids, etc
Skeletal: Ricketts, asymmetry, kyphoscoliosis etc
Other: cardiac, malignancy
51
Genes for EB
EB simplex - KRT 5 and 14
Junctional EB - laminin 332
Dystrophic EB - collagen 7
52
Hypohidrotic ectodermal dysplasia gene and features
```
Ectodysplasin - X linked most commonly
1. Sparse hair
2. Hypodontia - conical teeth
3. Reduced ability to sweat
4. Cutaneous: atopy, loss of dermatoglyphs, colloidon baby like
5. Dysmorphic facies
NORMAL NAILS
```
53
Hypohidrotic ectodermal dysplasia with immune deficiency gene and features
```
NEMO, AD
Milder than without immune def
1. Hypotrichosis
2. Hypodontia
3. Inability to sweat
4. Cutaneous: seb derm, erythrodermic
5. Pyogenic infection
```
54
Hidrotic ED - Clouston - gene and features
GJB6 mutation AD
Hair: wiry, brittle, pale
Nails: milky white
PPK - pebbled skin
55
Monilethrix gene
AD, Hb1 and 6 (KRT 81 and 86)
