Genoderm Flashcards
What is the genetic change in Incontinentia Pigmenti? What is the mode of inheritance?
IKBKG gene (prev called NEMO); X-linked
What are the stages of Incontinentia Pigmenti?
4 stages: Vesicular, Verrucous, Hyperpigmented and
Hypopigmented
Stage I: redness or inflammation of the skin (erythema), blisters, and boils
Stage II: the blisters develop a raised, wart-like (verrucous) appearance, and the lesions look like warts.
Stage III: between the ages of 6 and 12 months. In this phase, the skin is darkened (hyperpigmented). On the trunk, the dark is sometimes described as a “marble cake” appearance.
Stage IV: changes are pale or hypopigmented and hairless. There may be a diminished number of sweat glands
What is Incontinentia Pigmenti?
Genetic ectodermal dysplasia affecting the skin, hair, teeth, microvasculature, and central nervous system
- Ocular (20-70%)
- Neurologic (seizures, microcephaly, developmental delay)
- Dental abnormalities (>80% of cases)
- Absent teeth, conical teeth, delayed eruption
- Skeletal anomalies
- Cardiovascular anomalies (less common)
What are the main genes involved in Ectodermal Dysplasias?
EDA (X-linked)
p63
WNT
What is the phenotype of ED caused by mutations in EDA (X-linked)?
Hypohidrotic, or anhidrotic, ectodermal dysplasia (HED/EDA) is characterized by a triad of signs comprising sparse hair (hypotrichosis), abnormal or missing teeth (anodontia or hypodontia), and inability to sweat (anhidrosis or hypohidrosis)
What is the phenotype of p63 ED?
Split hand/foot malformation (electrodactyly)
lightly pigmented
sparse with patchy alopecia
hypohidrosis in some patients
Cleft lip/palate
Lacrimal duct defect
tooth abnormalities
What is the genetic change in Werner syndrome?
RECQL2 (WRN) Autosomal Recessive
What is the phenotype of Werner syndrome?
accelerated aging
Increased risk of malignancy – especially osteogenic sarcoma,
melanoma, thyroid cancer, breast cancer, hepatoma, leukemia
- Facial: beaked nose, prominent scalp veins and eyes, thin nose and
lips, micrognathia, midfacial hypoplasia - Lipoatrophy
- Mottled hyperpigmentation
- Scleroderma-like skin tightening
- Nails: dystrophic, hypoplastic, absent
- Joint hyperkeratosis
- Hypogonadism, laryngeal atrophy, osteosclerosis of extremities
- Bilateral cataracts, diabetes mellitus type II, osteoporosis
- Meningioma, sarcoma, thyroid cancer, melanoma
What is the gene change in Hutchinson-Gilford progeria syndrome?
De novo mutation in lamin A gene (LMNA) - point mutation
What is the phenotype of Hutchinson-Gilford progeria syndrome?
Facial feature:
* Prominent superficial scalp (and body) veins
* Perioral and nasolabial cyanosis
* Thin beaked nose, small mouth
* Frontal bossing
Clinical features:
* Normal at birth
* Poor growth, poor weight gain in 1st year of life
* Skin dry, thin. Alopecia
* Scleroderma-like features trunk, thigh, buttock, lower abdomen – usually by 3yo
* Early signs of photodamage e.g lentigo
* Delay in eruption of primary and secondary dentition
* Osteopenia with fractures 25
What are the two most common genes associated with Epidermolysis Bullosa Simplex?
KRT5 and KRT14 (encodes for Keratin 5 and Keratin 14)
What is the skin manifestation in Epidermolysis Bullosa Simplex?
Blisters of the basal layer of epidermis.
What is the most common genetic change in Junctional Epidermolysis Bullosa?
Integrin alpha 6 beta 4
What is the skin manifestation in Junctional Epidermolysis Bullosa?
Blisters of the lamina lucida
What is the most common genetic change in Dystrophic Epidermolysis Bullosa?
COL7A1
