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Dermatological Disorders (Ichthyosis
Defined by dry, scaly skin
that…
Dermatological Disorders
Ichthyosis
Defined by dry, scaly skin
that varies in severity
depending on the type
Syndromes with Ichthyosis
CHILD Syndrome
Conradi-Hünermann Syndrome
Keratitis-ichthyosis-deafness syndrome
Netherton Syndrome
Neutral Lipid Storage Disease with Ichthyosis
Adult Refsum Disease
Ichthyosis and Male Hypogonadism
Sjögren-Larsson Syndrome
Gaucher Disease, type 2
Ichthyosis Vulgaris
- Very common
- Presents in childhood
- Dominant/Semi-dominant
- 1 in 250 in childhood
- Scaly skin --> manage with lotions
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X-Linked Ichthyosis
- Mild disorder of keratinization
- Steroid sulatase deficiency
- 90% complete or partial STS gene deletions
- Increased plasma cholesterol-sulfate
- Pregnancy Issues: undetectable estriol in MS screen; insufficient cervical dilation
- Presents in birth or infancy
- Dry, scaly skin* (most prevalent finding)
- Teeth and hair findings
- Corneal opacities
- 25% cataract findings; doesn't affect vision
1 in 2,000 to 1 in 6,000 in males
Most have completely deleted gene
Others have contiguous gene deletion; seen with other diseases
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Epidermolysis Bullosa
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Junctional
- Separation above basement membrane of dermis
- Non-scarring, atrophy with time
- Patchy, absent hair
- Early onset osteoporosis
- AR
- Present in areas in addition to hands and feet
- Multiple genes
Laminin 5 subunits: LAMB3, LAMA3, LAMC2, integrin, XVII collagen
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Dystrophic
- Separation below basement membrane
- Scarring
- Type VII collagen: COL7A1 gene
- Both AD and AR
- Limb abnormalities
Almost complete syndactyly
3 Major Subtypes
- Dominant DEB (DDEB)
- Recessive DEB, generalized other (RDEB-O)
- Severe generalized (RDEB-sev-gen)
Hyperpigmentation
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Patchy Hyperpigmentation
Incontinentia Pigmenti
- X-Linked Dominant
- Skin
- Hair: thin, sparse
- Teeth: missing, small, abnormal
- Nails: hypoplastic
- Breast: supernumerary nipples
- Eye
- CNS
- Streaky Hyperpigmentation
First, blisters form
Then they heal over
Hyperpigmentation is left over in a streaky pattern
GENETICS OF IP
- Presents as early as infancy
- IKBKG (previously NEMO) gene, Xq28
80% caused by deletion of exons 4-10
- De novo mutations are more likely on paternal X
- Females primarily affected
- Affected males have been reported: 47, XXY; somatic mosaicism
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Focal Dermal Hypoplasia
Clinical Findings
- Skin abnormalities
(hyperpigmentation, hypopigmentation, cutis aplasia)
- Sparse or absent hair
- Dysplastic, hypoplastic or ridged nails
- Limb abnormalities (Syndactyly, Oligodactyly)
Genetics
- Mutations in PORCN gene
- X-Linked Dominant
- Lethal in males
- High de novo rate
-
Hypopigmentation
Albinism
A defect of melanin production
that results in little or no color (pigment) in the skin, hair, and eyes
Eye Findings in Albinism
- Nystagmus
- Reduced iris pigment w/iris translucency
- Decreased retinal pigment
- Foveal hypoplasia with decreased visual acuity
- Misrouting of optic nerves with alternating strabismus and decreased sterepscopic vision
- Majority of people with Albinism are legally blind

Reduced Iris Pigment 
Hypoplastic Fovea
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Ocular Ablinism
1 in 50,000 to 60,000
X-Linked GPR143 gene
Significant eye findings
Minor skin manifestations
Female carriers have iris transillumination and retinal hypopigmentation
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Oculocutaneous Albinism
OCA 3
Rufus-red-Albinism
1 in 8,500 in Southern Africa
TRYP1 gene
Some increase in pigment over time
Reddish hair
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OCA1
1 in 40,000
TYR gene (only one gene, easy to DX)
Least pigment of all OCA's
1 in 100 carriers

OCA1B

OCA1A
- White hair
- Non-tanning skin
- Fully translucent eyes, do not darken with age
More severe
OCA2
Incidences:
1 in 37,000 whites
1 in 15,000 blacks
1 in 3,700 Southern Africans (Bantu-speaking)
OCA2 (P gene) mutations
Pigmented hair at birth, usually do not tan, irises have some pigment, some freckles or nevi
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Patchy Hypopigmentation
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Hypomelanosis of Ito
- Pigmentary mosaicism
- No inflammatory stages (like in Incontinentia Pigmenti)
- Can have anomalies, CNS abnormalities, ID
- Chromosomal mosaicism, Xp11 abnormalities
- Mostly sporadic
- Hand anomalies (clinodactyly, syndactyly, polydactyly)
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Melanin Production
- No melanin is produced
- Melanosomes are not made (carry the melanin)
- Melanosome does not get to where it needs to be (melanin is loaded properly)
- Depends on TYR metabolism (People w/PKU therefore may have some albinism)
Ectodermal Dysplasia
Common Phenotypes
- Teeth - missing, pointed, widely-spaced, prone to cavities
- Hair - absent, sparse, thin, very light in color, excessively brittle, curly, or twisted
- Nails - Thick, thin, abnormally shaped, discolored, ridged, slow-growing, or brittle
- Sweat Glands - inability to perspire
- Skin - Thin, pale, dry, scaly, easily irritated, prine to rashes, infections and sunburn, thick over palms and sole
- Other Abnormalities may be present
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Hidrotic
Can sweat, but other ectoderm anomalies
HED2 (Clouston Syndrome)
- Normal sweating
- Normal teeth
- Nail hypoplasia and nail deformities
- Partial to total absence of hair
- Finger clubbing
- Skin hyperpigmentation over joints
- Normal teeth
- Thickened skin on palms and soles

Alopecia
Nail Hypoplasia
in HED2
GENETICS
- AD
- Variable expressivity
- Caused by mutations in GJB6 (Connexin 30)
(So you can see this in individuals with Deafness)
- DTR in almost 100% looking for 4 mutations
p.Gly11Arg - French. French-Canadian,
African, Spanish, Scottish-Irish, and Chines
p.Ala88Val - Indian, Malaysian, and Welsh
p.Asp50Asn - Ashkenazi Jewish
p.Val37Glu - a simplex case of Scottish origin
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Rapp Hodgkin Syndrome
Caused by mutations in one of the same genes in EEC
Likely to belong to a spectrum
- Ectodermal dysplasia
- Clefting
- Unsual Facies
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ED4 (HED with CL/P)
Particular gene on Chromosome 11
Seen in consanguinous couples
- Scanty eyebrows, eyelashes, scalp hair
- Striking teeth changes
- CL/P
- Webbing of fingers and toes
- Nail dystrophy
- Normal sweating
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