Pediatrics Flashcards
1
Q
Form of Oculocutaneous albinism with complete loss of pigment at birth, gray blue irides
Gene?
Other associated features?
A
OCA1a: TYR (absent); tyrosinase negative
Markedly decreased visual acuity
Increased risk of SCC
2
Q
Form of oculocutaneous albinism with no pigmentation at birth, but develop some pigmentation over time
Both amelanotic and pigmented nevi
Associated complications?
A
OCA1b; TYR (decreased to 5-10% of normal); otherwise known as yellow mutant albinism
Milder ocular complications than OCA1a
Temperature sensitive variant (OCA1b TS): Functions only at cool sites
Where would the pigment be?
3
Q
Most common form of oculocutaneous albinism
Africans
Light Brown Hair
Gray/Tan Irides
Other conditions with similar skin findings
A
OCA 2; (P gene; pink-eyed dilution)
Tyrosinase positive
1% of Prader-Willi and Angelman syndrome (mutation on 15q, has OCA2 gene)
4
Q
Very Rare Oculocutaneous Albinism
Africa and New Guinea
Reddish-Brown skin and red hair
Blue-Brown Irides
A
OCA 3; TYRP1
5
Q
OCA4
Population?
Clinical Presentation?
Gene?
A
Japan, 25% of OCA
Variable skin, similar to OCA2
solute carrier family 45; member 2 (SLC45A2); Formerly MATP
6
Q
Oculocutaneous Albinism
What is the problem?
Which cutaneous malignancies are they at risk for?
Why?
A
abnormal melanin, melanosome biosynthesis and transport (skin, hair, eyes)
SCC (most common), BCC, and melanoma
They have normal number of melanocytes, but decreased melanin
7
Q
What is this condition?
What is the gene mutation?
What are the characteristic changes in the affected cells?
What are associated systemic symptoms? (Hint three primary organ systems)
A
Chediak-Higashi
Oculocutaneous albinism (only slivery hair with eye)
Gene: LYST/CHS1
Impaired melanosomes (giant), platelet granules, giant PMN granules
Blood: Prolonged Bleeding Time; lymphoproliferative accellerated phase/HPS (death by age 10)
Neurological degeneration
Immunodeficiency: EBV, gingivitis, periodontitis
8
Q
What is the name of this syndrome?
What are the types?
What are the genes associated with each type?
What are the systemic features of this disease?
Other Similar syndromes?
A
Griscelli (all AR)
Aberrant translocation of melanosomes along microtubules
Trichoscopy: large and irregularly spaced melanin
Normal granules, no giant melanosomes
GS1: (MYO5A) Neuro
GS2: (RAB27A) Immunodeficiency with HLH
GS3: (MLPH)) skin limited
Elejalde: Variant of GS1?
9
Q
Puerto Rican with light hair, multiple bruises, who presents with progressive shortness of breath.
1) Disease?
2) Mutation?
3) What is the main problem?
4) Other systemic complications?
5) Most common cause of death?
A
1) Hermansky-Pudlak
2) AR (HPS1-HPS9)
3) Accumulation of ceroid lipofuscin
Disorder of lysosomal-related organelles (melanosomes, platelet dense granules)
4) Bleeding diathesis
Pale Irides: photophobia, strabismus, nystagmus
granulomatous colitis, progressive pulmonary fibrosis, cardiomyopathy, and renal failure
5) pulmonary fibrosis
10
Q
Disease?
Inheritance?
Mutation?
Other Internal Sequelae?
A
Piebaldism
AD
c-KIT protooncogene or zinc finger (SNAI2, SLUG)
White forelock +/- adjacent leukoderma
No systemic involvement
11
Q
What is the disease?
How many Types?
Mutations?
Characteristic features?
A
Waardenburg Syndrome
AD
white forelock, heterochromia irides, broad nasal root, and dystopia canthorum
WS1: PAX3
WS2: MITF (SNAI2)
WS3: PAX3
WS4: SOX10, EDNRB, EDN3
WS1: deafness (20-40%)
WS2: no dystopia canthorum, deafness common
WS3: Deafness + Upper limb abnormalities (hypoplasia, contracture, syndactyly)
WS4: WS1+ Hirschprungs
12
Q
Child with large hyperpigmented patch on the side of the chest
Disease?
Inheritance?
Gene?
Systemic Manifestations?
Laboratory?
A
1) McCune-Albright
2) Non-inherited, post-zygotic, F>M
3) GNAS1
4) CALMS, polyostotic fibrous dyplasia, endocrine dysfunction
4) bone pain, visible skeletal deformit, fractures
Precocious puberty, hyperthyroidism, acromegaly, hypophosphatemic rickets, and infantile Cushing syndrome
13
Q
Name of Disease?
Inheritance?
Gene?
Associated Findings?
A
Reticuate acropigmentation of Kitamura
AD (Japanese, rare)
ADAM10 (metaloproteinase and disintegrin)
lentigo-like hyperpigmented macules coalescing into a reticate pattern on the hands and feet
Palmoplantar its, abnormal dermatoglyphs
Histo: Increased melanin and melanocytes
14
Q
Disease?
Inheritance?
Gene/Mutation?
Subtype?
A
Dowling-Degos disease
AD
keratin 5
Galli-Galli (also keratin 5, but acantholysis on histology)
Can also have comedone-like lesions, pitted perioral scars, EIC, and Hidradenitis Suppurativa
15
Q
Name of disease?
Characteristic features?
A
Leiner’s disease
Seborrheic like dermatitis-> erythroderma
16
Q
What is this syndrome?
What is the gene and inheritance?
What is the mneumonic?
What are the associated systemic manifestations?
A
Noonan with multiple lentigines
PTPN11/SHP2, RAF1 (AD)
L(entigines), E(ECG), O (Ocular hypertelorism), P(ulmonic Stenosis), A(bnormal genitalia), R(etardating of growth), D(eafness)
Lentigines develop at 4-5 years of age
HCM
short stature, skeletal-mandibular prognatihism
Important: granular cell myoblastoma
17
Q
Diagnosis?
Gene? Inheritance?
Associated Systemic Manifestations?
A
Carney Complex (LAMB/NAME)
PRKAR1A (AD)
Multiple lentigines, ephelides, blue nevi (epithelioid); all fade with time, skin myxomas
Atrial myxomeas (50-80%)
Endocrine neoplasms (adrenocortiacal, pituitary, thyroid)
Sertoli cell tumor (aka testicular cancer)
Psammomatous melanocytic schwannoma
Breast ductal carcinoma
18
Q
Diagnosis?
Gene? Inheritance?
Systemic Manifestations?
A
Peutz-Jeghers
STK11/LBK, AD
Pigmented macules on lips, digits, and other mucosa by age 20
GI polyps
93% develop GI cancer before age 65, but also lung and breast cancer
19
Q
Diagnosis?
Gene, Inheritance?
Systemic Manifestations?
A
Laugier-Hunziker
Acquired!
Skin: pigmented macules on lips, buccal mucosa, genitals, melanonychia in 50%
No increased cancer risk
20
Q
Diagnosis?
Gene? Inheritance?
Skin Findings?
Systemic Manifestations
A
Cronkhite-Canada
Acquired
Older (age ~59, M>>F)
Lentigines of the hands, feet, and buccal mucosa
Nail Dystrophy, Alopecia
Intestinal polyposis-> Protein losing enteropathy and chronic diarrhead
21
Q
These hyperpigmented macules appeared within the first year of life, and are only where pictured, no other body areas are affected.
Diagnosis?
Gene? Inheritance?
Systemic Manifestations?
A
Centrofacial Lentiginosis (Touraine’s Syndrome)
Unknown, AD
Developmental delay, Seizures,
Mitral valve stenosis
Dwarfism, Skeletal abnormalities
Endocrine dysfunction
22
Q
Diagnosis?
Gene/Inheritance?
Skin Manifestations?
Systemic Manifestations?
A
Bannayan-Riley-Ruvalcaba
PTEN, AD -> failure of programmed cell death
Penile lentigines, lipomas
angiokeratomas, high flow vascular anomalies
macrocephaly, long philtrum, thin upper lip
facial acanthosis nigricans and verruca like lesions
Systemic: Developmental delay, intestinal polyps, hashimoto thyroiditis,
increased risk of malignancy?? (More evidence for CS)
23
Q
Disease?
Population?
Gene/ Inheritance?
Systemic Involvement?
A
Dyschromatosis Symmetrica Hereditaria
Japanese/Chinese
ADAR (SRAD), AD
RNA-specific adenosine deaminase
Presents by 6yo with dyschromia, hyper and hypopigmented macules on face and dorsal aspect of the extremities
No known systemic disease
24
Q
Disease?
Gene/Inheritance?
Sytemic Involvement
A
dyschromatosis universalis hereditaria
Japanese
ABCB6 (ATP binding cassette subfamily B), AD/AR
Generalized or torso dominant brown macules with scattered hypopigmented macules with a mottled appearance
Can have nail pterygium
Reported: short stature, idiopathic torsion dystonia, x-linked ocular albinism, neurosensory hearing loss
25
Disease?
Gene/Inheritance?
Skin Features?
Systemic Involvement?
Dyskeratosis Congenita
Zinsser-Engman-Cole syndrome
TERT, TERC (AD)
DKC1, TINF2 (XLR)-\> most common
Genes involved in telomere maintenance
Oral leukoplakia (premalignant), reticulated dyspigmentation, onychodystrophy (anonychia, pterygium, ridging, splitting
Palmoplantar hyperkeratosis,
Systemic: hematologic malignancies, squamous cell carcinoma of the mucosa (genital and oral)
pulmonary fibrosis
26
Disease?
Gene? Inheritance?
Skin Manifestations?
Systemic Manifestations?
Naegeli–Franceschetti– Jadassohn Syndrome/ Dermatopathia Pigmentosa Reticularis
keratin 14 (both NFJS and DPR)-\> allelic to ectodermal dysplasia disorders
Remember this is also the mutation in EB simplex
Skin:
NFJS (a-d,g): reticulated hyperpigmentation on the abdomen, improves after puberty
palmoplatar keratoderma, adermatoglyphia, hypohidrosis
**dental anomalies (not in DPR)**
DPR (e,f): diffuse non-scarring **alopecia (not in NFJS)**, **persistent** reticulated hyperpigmentation of the torso
27
**EB Simplex**
Level of Split
Inheritance?
Epidemiology?
Characteristic Features?
Intraepidermal split
AD (except for EBS with muscular dystrophy, AR)
Most common form
Does not heal with scarring
28
Diagnosis?
Mutation? Inheritance?
Exacerbating factors?
Other Skin Involvement?
Epidermolysis Bullosa Simplex (localized or webber-cockayne)
KRT 5, 14 (AD)
Worse with heat in summer, localized to sites of friction on soles \> palms
Can also rarely have oral ulcerations, palmoplantar hyperkeratosis, nail dystrophy
Normal Life Span
29
Diagnosis?
Characteristics?
Mutation/Inheritance?
Systemic Symptoms?
Epidermolysis Bullosa Simplex, Generalized Intermediate (Koebner)
Present at birth or in early infancy, bullae at any site of friction
Can have oral blisters, plamoplantar hyperkeratosis, +/- nail dystrophy
K5, K14 (AD)
Normal Life Span
30
Diagnosis?
Mutation/Inheritance?
Characteristic Features?
Age of Onset?
Systemic Involvement?
Epidermolysis Bullosa Simplex, Generalized Severe (Dowling-Meara)
KRT 5, KRT 14 (AD)
herpetiform clustered blisters, generalized blisters, may have some scarring
Oral blisters, ++ palmoplantar keratoderma, ++ nail dystrophy
Presents at birth or within the first few months
Clumped tonofilaments on EM
Usually normal life span, some early death from sepsis, anemia, or growth failure
31
Diagnosis?
Gene/Inheritance?
Age of Onset?
Characteristic Features?
Systemic Involvement?
Epidermolysis Bullosa Simplex with Mottled Pigmentation
KRT5, KRT 14 (AD)
childhood
Acral blisters, mottled pigmentation on the trunk and extremities
Nail dystrophy, puntate palmoplantar keratoderma
Normal lifespan
32
Diagnosis?
Gene/Inheritance?
Characteristic Features?
Age of Onset?
Systemic Involvement?
Other diseases with same mutation?
EBS with muscular dystrophy
Plectin (PLEC), AR
Generalized blisters that leave atrophic scars
Nail hyperkeratosis, dental abnormalities, scarring alopecia
Blistering at birth
Muscular dystrophy in infancy or later in life
Can have uretheral stricture, visual defects, and muscle weakness
EBS with pyloric atresia (Plectin, a6B4)
EBS-ogna (plectin)-\> mostly acral blistering
33
Junctional EB
Inheritance?
Mutations?
Basement Membrane Zone?
Clinical Characteristics?
Epidemiology?
AR
Laminin 332, BPAG 2, a6B4
Lamina Lucida
Enamal Hypoplasia-\> Dental Caries
Rarest form of EB
34
Disease?
Inheritance? Gene?
Age of Onset?
Systemic Involvement?
Junctional Epidermolysis Bullosa- Generalized Severe (Herlitz)
Laminin 332 (premature termination codon), AR
birth
generalized blisters health without scarring, buttocks, perioral, ears
hoarse cry (laryngeal involvement), perioral granulation tissue, nail dystrophy
Death within the first few years of life from respiratory failure or septicemia (90% by age 1)
FTT and anemia
35
Disease?
Gene? Inheritance?
Age of Onset?
Systemic Manifestations?
Junctional Epidermolysis Bullosa- Generalized Intermediate
Laminin 332, Col 17a (BPAG 2/180); AR
Birth
Generalized blisters and oral involvement, improves with age
heals with atrophic scars, **granulation tissues uncommon**
Nail dystrophy, dental enamal hypoplasia, corneal erosions
Survival into adulthood
36
Junctional EB with pyloric atresia
Mutation? Inheritance?
Age of Onset?
Systemic Complications?
a6B4, AR
Birth
Generalized Blisters, often with congenital aplasia cutis
GI, GU mucosal involvement
urethral strictures, hydronephrosis, malformed ears
~80% mortality in infancy
37
Disease?
Mutation, Inheritance?
Age of Onset?
Cutaneous Features?
Systemic Involvement?
Dominant Dystrophic Epidermolysis Bullosa
Coll 7 (missense mutation), AD
Birth
Cockayne-Touraine-\> Generalized, heal with scars and milia-\> improves over time
Pasini-\> all of the above + albopapuloid papules (see image)
Nail dystrophy, oral blisters
rare esophageal strictures, anemia
Survival Into Adulthood
38
(Ignore left upper image!)
Disease?
Gene, Inheritance?
Age of Onset?
Cutaneous Manifestations?
Systemic Manifestations
Recessive Dystrophic Epidermolysis Bullosa (Halopeau-Siemens Type)
Col 7 (stop?), AR
Birth
Generalized blistering
heal with milia and scarring -\> contracture of digits and limbs
(Pseudosyndactyly) Mitten deformities
Oral blisters, dental abnormalities
Scarring alopecia, corneal erosions
Esophageal strictures
Osteopenia, Anemia, Growth Failure
Dilated Cardiomyopathy
**Renal Failure, Agressive SCC**
SCC is leading cause od death (50% by age 35)
Renal Failure (12% mortality)
39
Recessive Dystrophic Epidermolysis Bullosa, Generalized Intermediate
Gene, Inheritance?
Age of Onset?
Cutaneous Manifestations?
Systemic Manifestations?
Also called, Non-Hallopeau-Siemens
Col 7, AR
Birth
Generalize blisters-Heal with milia and scarring-\> Can also have pseudosyndactyly
**Can improve slightly with age**
Systemic features include: rare cardiomyopathy, esophageal strictures, tracheolaryngeal stenosis, malnutrition failure to thrive.
40
Diagnosis?
Gene/Inheritance?
Age of Onset?
Cutaneous Features?
Systemic Involvement
Kindler Syndrome
FERMT1 (previously kindlin), AR
Duplication of the lamina dense on EM
Neonatal, improves over time
Poikiloderma, Acral blisters
Photosensitivity
Eczematous dermatitis, webbing of digits
Palmoplantar hyperkeratosis, Nail dystrophy, SCC of the oral mucosa
Normal lifespan
41
Disease?
Gene? Inheritance?
Cutaneous Manifestations?
Systemic Manifestations?
Basal Cell Nevus Syndrome (Gorlin)
PTCH, AD
PTCH inhibits SMO (which stimulates cell proliferation through GLI1/2)
Multiple BCCs appear around puberty-\> appear clinically more like nevi, SK, milia, acrochordons
Major Criteria:
1) \> 2 BCC or 1 before 20 years of age
2) Palmoplantar pits (\>3)
3) Odontogenic Cysts of the Jaw w/ histo ( at around age 10)
4) Calcification of the Flax Ceribri
5) Medulloblastoma (presents within the first 3 years of life)
6) First degree relative
Minor:
1) Bifib ribs
2) Cleft lip/palate
3) Skeletal: pectus excavatum, polydactyly
4) Macrocephaly (frontal bossing, hypertelorism)
5) Ovarian/Cardiac Fibroma
6) Lymphomesenteric cysts
7) Ocular abnormalities (cataract, coloboma, glaucoma)
Risk for Other Malignancy: Fibrosarcoma, Rhabdomyosarcoma
42
Diagnosis?
Gene? Inheritance?
Cutaneous Features?
Systemic Involvement
Birt Hogg Dube
BHD gene, encodes folliculin (AD)
Fibrofolliculoma, trichodiscoma, acrochordons
Renal Cell Carcinoma, Spontaneous Pneumothorax (Bullous Emphysema)
43
Diagnosis?
Gene? Inheritance?
Skin Findings?
Sytemic Involvement?
Brooke-Spiegler
CYLD, AD
deubiquinating enzyme for NEMO (which stimulates the NFKB pathway)
Trichoepitheliomas, cylindromas, spiradenomas, basal cell carciomas\*
Salivary and Parotid Neoplasms\*
44
Wermer Syndrome
Other Name?
Gene, Inheritance
Cutaneous Findings?
Systemic Involvement?
MEN 1
MEN1 (menin), AD
CALMS, angiofibromas, collagenomas, gingival papules (similar to tuberous sclerosis)
Pituitary, Parathyroid, Pancreas (Islet Cell, Gastrinoma, Glucagonoma, Insulinoma)
45
Diagnosis/Associated Syndrome?
Other Name?
Gene, Inheritance?
Cutaneous Manifestations?
Systemic Manifestations?
MEN IIa
Sipple Syndrome
RET, AD
macular and lichen amyloidosis
Medullary thyroid carcinoma, pheochromocytoma, hyperparathyroidism (2P)
46
Diagnosis?
Other Name?
Gene? Inheritance?
Cutaneous Manifestations?
Systemic Involvement
MEN 2B
Multiple Mucosal Neuroma Syndrome
RET, AD
mucosal neuromas, conjunctival neuromas, marfanoid habitus, thick lips
Medullary thyroid carcioma, pheochromocytoma, diffuse gangioneuromatosis
47
Diagnosis?
Gene? Inheritance?
Cutaneous Manifestations?
Systemic Involvement?
Cowden Syndrome
PTEN, AD
tricholemmomas, sclerotic fibromas, puncatate palmoplantar keratoses, acral keratoses, inverted follicular keratoses, lipomas
Oral cobblestone appearance
Thyroid: goiter, **follicular carcinoma**
Breast: fibrocystic disease, **adeno (most common Ca)**
GI: hamartomatous polyps
GU: uterine leiomyomas, **endometrial carcinoma**
Bone: craniomegaly, bone cysts
**Lhermitte-Duclos:** (dysplastic gangiocytoma of the cerebellum)-\> ataxia, seizures, increased ICP
48
Disease?
Gene, Inheritance?
Cutaneous Findings?
Systemic Involvement?
Gardner Syndrome, Familial Colorectal Polyposis
APC (adenomatous polyposis coli)-\> tumor suppressor that regulates B-catenin
Skin: Supernumerary teeth (photo), Epidermoid Cysts w/ pilomatrical changes, fibromas, lipomas
GI: premalignant polyposis (prophylactic colectomy at 20-30), d**esm**oid tumors
Ocular: congenital hypertrophy of the retinal pigment epithelium (CHRPE, 70%)
Bone: osteomas (80%), odontomas
Adrenal adenomas
Other Cancer: papillary thryoid carcinoma, hepatoblastoma, sarcomas, pancreatic carcinomas
**Turcot:** Glioblastoma and medulloblastomas
49
PHACE (what does it stand for?)
Infantile Hemangioma
Cerebrovascular anomalies are most common
Posterior Fossa
Hemangioma
Arterial
Cardiac/Coarct
Eye
Sternal Cleft
50
LUMBAR (meaning)
Lower Body Hemangioma
Urogenital
Myelomeningocele
Bony
Anorectal
Renal
51
Neonatal Hemangiomatosis
Number cut off
\> 5 hemangiomas
Benign (small, limited to skin)
Diffuse (liver, brain, eyes, etc)
Screen: LFTs
Complications: High Output Heart Failure
52
Kasaback-Merrit
Consuptive Coagulopathy
Tufted and KHE
low plts, elevated D-dimer, low fibrinogen
Complications: High Output Heart Failure
Treatment: corticosteroids, vincristine, sirolimus
NOT propranolol
53
Mutation in Capillary Malformations
GNAQ
54
Encephalotrigeminal Angiomatosis
Sturge-Weber
V1 and V2\> V3
55
Phakomatosis Pigmentokeratotica
Nevus Spilus + Nevus sebaceous
HRAS mutation
Hypophosphatemic rickets
56
Klippel-Trenaunay Syndrome
PIK3CA
Capillary Malformation
Venous or Lymphatic
Usually Lower Extremity
Limb Overgrowth
Chronic Intravascular Coagulopathy
High Output Heart Failure
57
Proteus Syndrome
AKT1
Overgrowth Syndrome (does not co-localize with CM)
CM/VM/LM
CALM
Epidermal Nevi
Connective tissue nevi
Neoplasms:
Ovarian Cystadenoma
58
Beckwith-Wiedemann
Gigantism
Facial CM
Macroglosia
Visceromegaly
**Wilms tumor (nephroblastoma)**
59
Venous Malformations
Mutation?
VMCM (TIE2), same with sporadic VM
red to purple soft nodule or plaque
slow flow
phleboliths
may have elevated d-dimer, low fibrinogen
60
Enchondromas with multiple angiomas
Maffucci
IDH1/IDH2 mutations, previously PTHR1
venous malformations of hands and feet
enchondromas (50% risk of chrondrosarcoma)
61
Glomulovenous Malformations
AD
GLMN
Infancy or childhood with multiple compressible nodules
62
Blue Rubber Bleb Nevus
Usually sporadic
63
Microcystic Lymphatic Malformations
Stains
D2-40 (podoplanin) and LYVE-1 stains endothelial cells
64
Macrocystic Lymphatic Malformation
Association
Cystic Hygroma
Turner, Down, Noonan
Lymphatic malformations have increased risk of infection
Also stain with D2-40 and LYVE
Complications: Airway obstruction or pneumonia
65
Nonne-Milroy Syndrome
Congenital Lymphedema
AD
FLT4 gene (VEGFR3)
Presents at birth with bilateral lymphedema
Can have hydrocoele
66
Lymphedema-Distichiasis Syndrome
AD
FOXC2
Pre-pubertal onset
Distichiasis= extra set of eyelashes
67
Parkes-Weber
May be subset of CM-AVM syndrome (same mutation in ~ 50%)
RASA-1 Mutation
AVM is stimulated to grow by puberty, pregnancy, trauma
High output heart failure
68
AVM Location
Most commonly cephalic (70%)
40% at birth others later become visible
69
Cobb Syndrome
cutaneomeningospinal angiomatosis
Spinal hemangioma or AVM
Overlying capillary malformation
70
CMTC
natural history
present at birth
fades over first 2-3 years
Associated with limb hyper or hypoplasia, neurological abnormalities, optho
Adams-Oliver Syndrome (SCAP aplasia cutis, CM, transverse limb deformities)
71
Angiokeratoma Corporis Diffusum
Associations
Fabrys, X-linked recessive (a--gluosidase)
GM1 gangliosidosis (AR), fucosidosis (AR), etc
72
Fabry's disease
X-linked recessive
a-glucosidase deficiency
Deposition of glycosphingolipids in blood vessels, nerves, smooth muscle, eyes)
Whorl-like corneal opacities/posterior cataracts
Neuro (paresthesias, cardiac arrhythmias, etc)
Strokes
Renal Failure (maltese crosses)
Angiokeratoma corporis diffusum (puberty)
73
Diagnosis
Unilateral Nevoid Telangiectasia
Acquired Idiopathic
74
Diagnosis
Angioma Serpiginosum
Common in females (90%)
Common on lower extremities
75
Diagnosis
**Generalized Essential Telangiectasia**
Begins on legs then spreads proximally
Does not involve face
More common in females
Can be associated with paresthesias
76
Diagnosis
AD
TELAB1
Begins at 2-12 years of age
telangiestasias with surrounding pallor on face, arms, upper trunk
77
Diagnosis
Hereditary Hemorrhagic Telangiectasia
AD
HHT1 (endoglin), HHT2 (ALK1)
Epistaxis, Anemia
AVMs: pulm (HHT-1), cerebral, hepatic (HHT-2)
78
Diagnosis
Ataxia Telangiectasia
ATM gene (Autosomal Recessive)
regulates cell cycle, cellular response to DNA damage
INCREASED DAMAGE WITH IONIZING RADIATION
bulbar/conjunctival telangiectasias starting at 3-5 years
Truncal taxia first presenting sign
Non-infectious Granulomas
Immunodeficiency (increased IgM all others decreased)
Increased risk of leukemia, lymphoma, breast Ca
79
ATM Carriers association
Ataxia Telangiectasia gene
Breast cancer in femal carriers
80
Jadassohn-Lewandowski
Pachyonychia congenita Type I
Keratin 6a and 16
benign oral leukoplakia
follicular hyperkeratosis
All have local keratodermal, plantar pain, and onychodystrophy
81
Jackson-Lawler
Pachyonychia congenita, Type II
keratin 6b and 17
natal teeth and steatocystomas
82
Christ-Siemens-Touraine syndrome
Hypohidrotic ectodermal dysplasia
**XLR** (ED1) ectodysplasin
decreased sweating, hypotrichosis, abnormal dentition
frontal bossing, large nostrils
peg-shaped, conical, or missing teeth
83
Clouston
Hydrotic Ectodermal dysplasia
AD (GJB6/connexin 30)
Onychodystrophy, thin hair, palmoplantar keratoderma
Normal sweating, normal dentition
84
Hay=Wells
Anyloblepharon-ectodermal dysplasia-clefting syndrome
Erosive scalp dermatitis
colloidion membrane baby
congenital fusion of eyelids
mutation **p63 (transcription factor for ectodermal development)**
85
Rapp-Hodgkin
p63 associated
clefting
small narrow nails
conical teeth
86
Ectrodactyly ectodermal dysplasia-cleft lip/palate syndrome
Lobster claw
hearing loss
PPK
GU abnormalities
p63 mutation, AD
87
Rubinstein-Taybi
sporadic, CREBBP
**racquet nails (brachyonychia)**
CM
heart defects
**multiple pilomatricomas**
88
Child sheds all hair after brith, and hair never grows back. As a teen they develop milia-like papules.
Atrichia with papules
Hairless gene mutation
May be associated with vitamin D resistant rickets
89
Diagnosis
Pili triangulati et canaliculi
Uncombable hair syndrome
Begins in infancy
Can be associated with oncychodystrophy and ectodermal dysplasias
90
Diagnosis?
Mutation?
Monilethrix
KRT 81,83,86 (AD)
DSG4 (AR)
Normal hair at birth, becomes short and brittle during infancy
associated with koilonychia, keratosis pilaris
91
Name of finding
Associated conditions
Pili Torti
Menkes kinky hair
Bazex-Dupre-Christol
Rombo
Bjornstad
Crandall
92
Name of Finding?
Associated Syndromes?
Trichorhexis nodosa
Most common hair shaft anomaly
Mostly acquired, but also AD form
Netherton
Trichothiodystrophy
Arginocuccinic aciduria
Citrullinemia
Oculo-dental-ditial dysplasia
93
Name of Finding?
Association?
Trichorhexis Invaginata
Netherton Syndrome (spink 5, AR)
94
Condition?
Children vs Adults
Alopecia Mucinosa (Follicular Mucinosis)
In children rarely associated with CTCL
95
Disease?
Inheritance?
Association?
Treatment?
Loose Anagen Syndrome
sporadic, but can be AD
Fair, fine, limp, diffusely thinned hair
Noonan-like syndrome (SHOC2)
Improves with time
96
Diagnosis
Nevoid Hypertrichosis
Localized patches to terminal hair growth, different from other hair
Rare association with neurodevelopmental abnormalities
97
Keratosis Pilaris
Associations
Trisomy 21
Atopy, xerosis, ichthyosis vulgaris
ectodermal dysplasias?
98
Diagnosis
Association
keratosis pilaris atrophicans, atrophoderma vermiculatums subtype
Rombo syndrome
Trisomy 21
99
Diagnosis?
Associations?
Keratosis Pilaris atrophicans, ulerythema ophyrogenes subtype
sporadic, AD
Cardio-facio-cutaneous sydrome
Noonan syndrome
Cornelia de Lange syndrome
Rubenstein-Tybi syndrome
100
Keratosis Follciularis Spinulosa Decalvans Subtype
XLR (SSAT)
progressive scarring alopecia
extensive keratosis pilaris
101
Diagnosis?
Associations?
Eruptive Vellus Hair Cyst
**hyperpigmented** follicular papules
Hidrotic ectodermal dysplasia
Hypohidrotic ectodermal dysplasia
Pachyonychia congenita
102
Diagnosis?
Nutritional Deficiency
103
Acrodermatitis Enteropathica
Mutation?
AR when inherited
SLC39A4 (zinc specific transporter ZIP4)
104
Heritable Disease Associated
Hartnup disease
AR, SLC6A19
neutral amino acid transporter
low tryptophan -\> low nicotinic acid
pellagra-like symptoms
105
Short child with mousy odor to urine
phenylketonuria
skin: hypopigmented, eczema, photosensitivity, sclerodermoid changes
mental retardation
Rx: low phenylalanine diet, avoid aspartame
106
Homocystinuria, skin findings
Livedo reticularis, leg ulcers
AR, cystathionine beta-synthetase deficiency
Diet with pyridoxine (B6)
107
Baby with orange urine
Lesch-Nyhan syndrome
XLR, HGPRT gene
Intellectual impairment
Self-mutilation
Gout
Rx: Allopurinol
108
Prolidase deficiency
Progressive lower extremity ulcers
Recalcitrant
Intellectual impairment
Hypertelorism, beaked nose, frontal bossing
109
Alagille syndrome
AD, JAG1 (cell fates in early development)
Skin: Tuberous xanthomas
High cholesterol (\> 200 mg/dl), TAG (\> 500-2000 mg/dl)
congenital intrahepatic biliary hypoplasia
Rx: liver transplant or death (\< age 5)
110
XLR mutation in IDS gene
Hunter syndrome
Coarse Facies
Hypertrichosis
Pebbled ivory-colored plaques
cardiomyopathy
progressive neurodegeneration
hearing loss
retinal pigmentation
111
Alkaptonuria
AR, homogentistic 1,2-dioxygenase (HGO) gene
Blue-gray pigmentation of the ears, sclera
Mitral/Aortic valvulitis
Severe Arthritis
112
Absent and Decreased Lamellar Bodies Occur in These Conditions
Harlequin fetus
Flegel's disease
113
Diagnosis
Mutations, Etc
Cutis Laxa
AD (fibulin, elastin): begins in early adulthood
AR (FBLN5): skin + internal organ (hypoplastic lungs, GU)
XLR (ATP7A): Occipital horn syndrome (wedge shapped occipital calcifications
114
Drug Induced cutis laxa/PXE
penicillamine
115
ABCC6
PXE
AR
\*\*mineralization of elastic tissue\*\*
Ocular: Angiod streaks (Bruch's membrane rupture), Mottling of retinal pigment
CV: renovascular hypertension, mitral valve prolaspse, MI, stroke
OB: Miscarriage
116
COL1A1
Osteogenesis Imperfecta
Types
1) mild, fractures
2) fatal in perinatal
3) progressive (death in 3rd and 4th decade, due to restrictive lung disease (scoliosis))
4) ??, normal life span
Features:
Blue Sclera
Translucent Skin
Brittle Bones, Fractures
Scoliosis
Beaded Ribs
117
Classical Ehlers-Danlos
Type I
Type II
Col5A1, Col5A2 (AD)
Hyperextensibility/mobility
Easy Bruising
**Molluscoid pseudotumors**
**+ Gorlin sign** (tongue touch nose)
118
Ehlers-Danlos, Type III
Hypermobility form
TNXB (AD)
tenascin X
Hypermobility, arthritis
**Dislocations and subluxations**
119
Ehlers-Danlos Type IV
Vascular
COL3A1, AD
blue sclera
extensive bruising
early varicosities
visible veins
**rupture of bowel (sigmoid), uterus, or arteries**
120
Ehlers-Danlos, Type VI
Kyphoscoliotic
lysl hydroxylase (PLOD1); AR
hypermobility
marfanoid
severe scoliosis
**EYE (ruptured globe, retinal detachment)**
121
EDS, Type VII a,b
Arthrochalasic
COL1A1, COL1A2 (AD)
**most severe hypermobility**
Severe subluxations and dislocations
**congenital hip dislocation**
mitral valve prolapse
postural orthostatic tachycardia syndrome
122
EDS, Type VIIc
Dermatosparaxis
Procollagen N-proteinase **(ADAMTS2)**; AR
**sagging, redundant skin**
premature rupture of fetal membranes
123
EDS, Type VIII
Periodontitis
AD
124
FBN1
Marfan syndrome
fibrillin-1, AD
Tall, long extremities
striae
EPS
Skeletal: arachnodactyly
Ocular: ectopia lentis (downward displacement)
CV: dilation of the ascending aorta, mitral valve prolapse
Pulm: spontaneous pneumothroax
125
LEMD3/MAN1
Buschke-Ollendorf
AD, LEMD3/MAN1 -\> increased TGF-B signaling
dermatofibrosis lenticularis disseminata (collagen type nevus)
osteopoikilosis (spotted bones)
126
ANTXR2/CMG2
Infantile systemic hyalinosis (begins within 6 months and death before 2 years) and juvenile hyaline fibromatosis (survival into adulthood)
ANTXR2/CMG2 -\> mutation leads to hyalinized fibrous issue
AR
**small pearly papules on ears and face**
joint contractures
127
ECM1
lipoid proteinosis
AR, extracellular matrix protein
Hoarse cry (1st sign)
vesicles and hemorrhagic crusts-\> ice pick scars
hyaline deposition-\> beaded eyelid papules
woody, thick tongue, inability to protrude
respiratory difficulty
seizures (bean-shaped calcifications in temporal lobes/hippocampus)
Histo: deposits are PAS+, diastase resistant
128
PORCN
Focal dermal hypoplasia (Goltz, Goltz-Gorlin)
**XLD,** lethal in males
Blaschkoid areas of hypoplasia, telangiectasias
yellow, reddish nodular outpouchings
raspberry papillomas (lips and anogenital)
Skeletal: ectrodactyly, osteopathia striata
Optho: colobomas
Dental: hypoplastic or absent teeth; delayed eruption
F: female, xld
O: Osteopathia striata
C: Coloboma
A: Aplasia ectoderm elemens
L: lobster claw
129
fibrillin 2
Contengial contractual arachnodactyly
FBN2, AD
marfanoid
congential contractures of large and small joints
crumpled ears
mitral valve prolapse, aortic root dilation
130
LMNA
Restrictive dermopathy (tight skin contracture syndrome)
**LMNA** (lamin-A) or ZMPSTE24 (AR)
polyhydramnios, fetal akinesia
**taut translucent skin**
**restrictive pulmonary disease**
**death shortly after birth**
131
FBN1, but not Marfan
Stiff Skin Syndrome
**fibrillin-1** (AD)
progressive development of stony-hard skin on thighs, buttocks, lower back
Histology: fascial sclerosis
132
Cytokines involved in autoinflammatory syndromes
IFN-a, IFN-y, IL-6, IL-1, TNF-a
133
Adult onset inflammatory syndromes
FMF and TRAPs
134
CIAS-1/NLRP3
AD mutation in all cryopyrin associated periodic syndromes
1) Familial cold autoinflammatory syndrome: infancy, cold urticaria (short minutes-days)
2) Muckle-Wells syndrome: any age onset, abdominal pain, hearing loss, wide spread urticaria; lasting 1-2 days; **secondary AA with significant morbidity**
3) NOMID/CINCA: neonatal, wide spread urticaria, **dysmorphic facies, arthropathy, blindness, aseptic meningitis;** continuous febrile attacks, mortality in childhood if untreated
**RX**: IL-1 antagonists
135
MEFV
Familial Mediterranean fever
MEFV, encodes pyrin/marenostrin (AR)
Any age onset
erysipelas-like rash on legs and feet
attacks last 1-3 days
**secondary AA (prevented by colchicine)**
**RX:** colchicine, NSAIDs, IL-1 antagonists, TNF-a
136
**TNFRSF1A**
TRAPS, AD
Any age of onset
painful, migratory, serpiginous plaques
serositis, myalgias
Attacks: 1-6 weeks
**Secondary AA**
Labs: decreased TNF-a receptor levels
**Rx:** corticosteroids, TNF-a antagonists
137
MVK
Hyper-IgD syndrome (Mevalonate kinase deficiency)
mevalonate kinase, AR
Onset in infancy
polymorphous rashes, arthralgia, abdominal pain
Attacks up to 7 days
Labs: Increased IgD
**RX**: IL-1 antagonists, TNF-a antagonists
138
PSTPIP1/CD2BP1
PAPA (Pyogenic arthritis, pyoderma gangrenosum, acne syndrome)
proline-serine-threonine photphatase interacting protein
**AD**
Onset in **childhood**
PG, nodulocystic acne, pyogenic oligoarthritis
**afebrile**
Rx: TNF-a, IL-1
139
IL1RN
Deficiency of the IL-1 receptor antagonist (DIRA)
AR
Onset neonatal
Skin: neutrophilic pustular dermatosis, ichthyosis
sterile osteomyelitis
afebrile
**IL-1** antagonists
140
IL36RN
Generalized pustular psoriasis/deficiency of the IL-36 receptor antagonist (DITRA)
AR
Onset: infancy, childhood
Skin: generalized pustular psoriasis
Systemic: **Multi-organ failure**
All psoriasis Rx are used
141
**NOD2/CARD15**
Blau syndrome/early sarcoidosis
nucleotide binding oligomerization domain2/caspase recruitment domain
AD
childhood onset
sarcoidal granulomas, ichthyosiform dermatitis
fever, arthritis, synovitis
**RX:** steroids, IL-1 antagonists, TNF-a antagonists
142
Most common neurofibromatosis
90% NF1
143
von Recklinghausen's disease
NF-1
neurofibromin (AD, 50% sporadic)
tumor suppressor, Ras pathway
Skin: neurofibroma, malignant peripheral nerve sheath tumor (10% risk in plexiform)
Lisch nodules (\> 90% by 10 yo)
Spehnoid wing dysplasia (exopthalmos)
Congenital tibial pseudoarthroses
Optic glioma, and other neurotumors
Other: pheochromocytoma, **breast cancer**, Wilms tumor (nephroblastoma), CML, **nevus anemicus**,
144
NF1 Criteria
\>2 of the following:
6 CALM \> 0.5 cm (prepuberty), \> 1.5 (post)
Intertriginous freckling
plexiform neurofibroma
\> 2 lisch nodules
optic nerve glioma
pathogenomic skeletal dysplasia
affected 1st degree relative
145
SCH gene
NF2
schwannomin/merlin, AD
tumor suppressor
Symptoms start in 2nd decade
**bilateral vestibular schwannomas**
**subcutaneous neurofibromas (fewer)**
Poor prognosis; Multiple CNS tumors cause death
146
hamartin/tuberin
Tuberous Sclerosis complex
TSC1/TSC2, AD
tumor suppressor genes, mTOR pathway
adenoma sebaceum
ash-leaf macules (confetti pattern pretibially; **first cutaneous finding**)
Koenen tumors (periungual fibromas)
Neuro: **seizures (#1 cause of death),** cortical tubers, paraventricular calcification, giant cell astrocytoma
Renal: **angiomyolipomas**, RCC; renal failure (**#2 cause of death)**
Ocular: **retinal phakomas**
Cardiac: **Cardiac Rhabdomyomas** (WPW)
Dental: pits in enamal, gingival fibromas
Lung: pulmonary **lymphangioleiomyomatosis,** pulmonary cysts (pneumothroax)
147
Facial Angiofibroma Treatment
Rapamycin (mTOR inhibitor)
148
TSC Criteria
Diagnosis: requires mutation or two major criteria or one major and two minor
Major: \> 3 angiofibromas, \> 3 hypomelanotic macules, \> 2 ungual fibromas, shagreen patch (connective tissue nevus), retinal hamartomas, cortical dysplasias, subependymal nodules, giant cell astrocytoma, cardiac rhabdomyoma, lympangioleiomyomatosis, \> 2 antiomyolipomas
Minor: \> 3 dental enamel pits, \> 2 intraoral fibromas, confetti like skin lesions, nonrenal hamartomas, multiple renal cysts, retinal achromic patch
149
First manifestation of TSC
hypomelanotic macules
150
Timing for Koenens tumor
adolescence
151
NEMO
Incontinentia pigmenti
**XLD**
NEMO usually activates NFKB (which modulates cell proliferation, inflammation); **NEMO function is lost in IP**
lyonization in females results in blaschkoid pattern
Missense mutation in NEMO: hypohidrotic ectodermal dysplasia with immunodeficiency
Systemic: seizures, developmental delay, dental, ocular, breast
152
Stages of IP
1) Vesicular: birth to 1 month; eosinophilic spongiosis + apoptotic keratinocytes
2) Verrucous: up to 2 years; papillomatosis, acanthosis, hyperkeratosis, apoptotic cells-\> squamous eddies
3) Hyperpigmented: Up to adolescence; melanophages, pigment incontinence
4) Hypopigmented: may persist into adulthood; epidermal atrophy, loss of pilosebaceous units, eccrine glands, apoptotic cells
153
LMNA
Hutchinson-Gilford progeria
Lamin A, AD
abnormal nuclear envelope
Dysmorphic facies: enlarged head, micrognathia, small ears, beaked nose
high pitched voice
Symptoms begin at 6-18 months
sclerodermoid changes
rapid aging
atherosclerosis
Death by age 13 from CV disease
154
RECQL2/WRN
Werner syndrome
DNA helicase, AR
starts in 3rd and 4th decade
progressive alopecia
sclerodermatous/atropic acral/facial change
short stature, atherosclerosis
Increased risk of malignancy: **fibrosarcoma, osteogenic sarcoma**
Die in 50s from CV disease or malignancy
155
Xeroderma Pigmentosum
Gene?
Mechanism?
Most common?
XPA-\>XPG proteins
Genes: DDB1, ERCC3, ERCC2, DDB2, ERCC4, endonuclease (XPA-G), **AR**
nucleotide excision repair pathway
Most common: XPA and XPC
1000 fold increase in skin malignancy
BCC, SCC, melanoma, and fibrosarcoma
mean age at first is 8 yo
**XPB (ERCC3), XPD (ERCC2), XPG:** a/w cockayne overlap
**XPB, XPD:** a/w trichothiodystrophy
Neurodevelopmental complications (20-30% of XP: XPA and XPD)
**XPV** (post-replication repair pathway,DNA polymerase-n), **no neurological complications**
156
De Sanctis-Cacchione syndrome
XP with severe neurological deficits (ataxia, paralysis, deafness)
157
RECQL3
Bloom syndrome (congenital telangiectatic erythema)
BLM/RECQL3, AR
DNA helicase (characteristic chromosomal breakage and rearrangement on instability testing)
growth impairment, bird-like nose
photosensitivity
Low IgM, IgG
Respiratory and GI infections
Malignancy: lymphoma/leukemia, solid tissue tumors
158
RECQL4
Rothmund-Thomson (poikiloderma congenitale)
DNA helicase
1st year of life
erythema, blisters on cheeks, poikiloderma
acral keratoses, alopecia, dystrophic nails
Short stature, **absence or hypoplasia of thumbs, radius, and ulna**
juvenile cataracts
hypogonadism
**Malignancy:** osteosarcoma (14 yo), NMSC (SCC, 34 yo)
159
**ERCC8**
**ERCC6**
Cockayne syndrome
transcription coupled nucleotide excision repair,
ERCC6 (CCS-B) \> ERCC8 (CS-A) AR
**Neuro! progressive CNS deterioration/demyelination** Photosensitivity
* No increased risk of skin cancer*
* No pigmentary changes*
Short stature, **cachectic dwarfism**
Eyes: **salt and pepper retinopathy**
160
ERCC2
ERCC3
GTF2H5
C7Orf11
Trichothiodystrophy (Tay/ PIBIDS)
w/ photosensitivity: ERCC2, ERCC3, GTF2H5
w/o photosensitivity: C7Orf11, no ichthyosis
**brittle hair and nails (low cysteine)**
Photosensitivity **(no increased skin cancer)**
Ichthyosis
Brittle Hair (Tiger-tail, Trichoschisis, Trichorrhexis nodosa)
Intellectual Impairment
Decreased fertility/hypogonadism
PPK, **hypogammaglobinemia**
161
Hydroa vacciniforme
**UVA**
**EBV**
mean age= 8 yo
r/o EBV associated lymphoproliferative disorder
Usually resolves during adolescence
Rx: UVB, hydroxychloroquine, beta-carotene, thalidomide
162
HLA-DR4, DRB1\*0407
actinic prurigo
**native american**
**onset prior to age 10**
actinic chelitis
actinic conjunctivitis: epiphora= eye watering
lip biopsy with lymphoid follicle
decreased MED
Rx: UVB, **thalidomide**
163
Juvenile Plantar Dermatosis
boys\>girls
frictional irritant
smooth red plaques
Rx: absorbent socks, corticosteroids
164
Juvenile Spring Eruption
Boys, age 5-12
Trigger: **UVA, UVB, Visible Light**
early spring, variant of PMLE
papules-\> vesicles -\> crusting
Rx: UVB, sun protection
Usually stops after puberty
165
Diaper Dermatitis
9-12 months
glazed appearance, sparing skin folds (irritant)
granuloma gluteale infantum (see photo)
perianal pseudoverrucous papules and nodules
Jacquets erosive dermatitis
Diaper ointments
**avoid steroids in granuloma gluteale**
166
Diaper Candidiasis
beefy red erythema, satellite lesions
167
Acropustulosis of Infancy
birth-2 years
recurrent vesicopustules over palms, soles, and distal extremities
Spontaneously resolves by 3 years
168
Cutaneous Mastocytosis
c-KIT mutations
KIT= CD117
Urticaria Pigmentosa is most common
More lesions= more likely systemic symptoms
169
Diffuse Cutaneous Mastocytosis
infiltrated, red-brown, leathery plaques
increased risk of systemic symptoms and progression to sysemic mastocytosis
Imatinib for systemic mastocytosis with **FIP1L1-PDGFRA gene rearrangement**
170
Mast Cell Stains
typtase, toludine blue, giemsa, CD117 (KIT), Leder
171
Mast Cell Degranulators
Alcohol
Anticholinergics
NSAIDs
aspirin
narcotics
**polymyxin**
systemic anesthetics
172
Chronic Granulomatous Disease Mutation
X-linked recessive
CYBB
CYBA
carriers have increased risk of lupus
nitroblue tetrazolium test
173
WHIM mutation
CXCR4 (AD)
174
AD Hyper IgE
STAT3
175
AR HyperIgE
DOCK8
176
omenn syndrome
scid (but lad) + severe eczema, alopecia
RAG 1
RAG 2
177
SCID mutation
IL2RG (XLR)
ADA (AR)
JAK 3 (AR)
GVHD like skin changes
**No palpable lymph nodes**
178
Wiskott-Aldrich
XLR
WAS
encapsulated bacterial infections
eczematous dermatitis
thromboctyopenia
low IgM
lymphoma
179
IPEX
FOXP3
immunodeficiency
Polyendocrinopathy
x-linked
180
Collodion membrane association
lamellar ichthyosis
non-bullous congential erythroderma
Others: Sjogren-Larson, Laucher, Hay-Well (AEC), trichothiodystrophy, Netherton, ectodermal dysplasia, neutral lipid storage disease
181
Steroid sulfatase deficiency
X-linked recessive ichthyosis
adherent scales
spares flexures
+ lateral neck involvement (vs IV, which does not involve the neck)
**corneal opacities**
**cryptorchidism**
**testicular cancer**
**Prolonged labor**
182
Lamellar ichthyosis
**TGM1 (AR)**
**colloidion membrane**
**plate like scaling**
ABCA12
CYP4F22
CERS3
183
Congenital Ichtyosiform erythroderma
ALOXE3 (AR)
ALOX12B
collodion membrane (#1 cause)
erythroderma, white scale
flexures involved
184
Congenital self-healking collodion baby
TGM1, ALOX12B, ALOXE3
collodion resolves, no additional problems
185
Epidermolytic Ichthyosis
Bullous CIE
KRT 1, 10 (AD)
blistering at birth -\> hyperkeratosis in cobblestone pattern
186
Harlequin ichthyosis
ABCA12 (AR)
severe thick plates of scale at birth
Often neonatal death
187
Superficial epidermolytic ichthyosis
bullos of Siemens
KRT2 (AD)
Similar histology to EI, but only superficial scaling of flexural surfaces in adulthood
188
Ichthyosis hystrix Curth-Macklin
KRT1 (AD)
Clinically similar to epidermolytic ichthyosis
189
Ichthyosis en confetti
KRT 10
erythroderma/scaling-\> confetti like areas of scaling (revertant mosaicism)
joint contractures
190
Netherton
SPINK5 encodes LEKT1 (serine protease inhibitor)
191
Sjogren-Larsson
FALDH (fatty aldehyde dehydrogenase)
perifoveal white dots
di or tetraplegia
persistent itchy ichthyosis with palmoplantar keratoderma
192
Neutral Lipid Storage Disease
ABHD5 (AR)
CIE like phenotype
developmental delay
hepatomegaly
**peripheral smear with lipid vacuoles in granulocytes**
193
Refsum
Ichthyosis + Polyneuropathy
PHYH, PEX7 (AR)
Cerebellar ataxia
cardiomyopathy
retinitis pigmentosa
194
GJB2
Connexin 26
KID (Keratitis Ichthyosis Deafness) syndrome
AD
Skin: stippled palmoplantar keratoderma, well-demarcated erythematous plaques
sensorineural hearing impairment
blindness
SCC
Recurrent mucocutaneous infections
195
GJB3/GJB4
Connexin 31 and 30.3
AD
Erythrokeratoderma variabilis
Geographic hyperkeratotic plaques
plamoplantar keratoderma
burning/stinging sensation with transient erythematous patches
196
GJB4, LOR
Progressive symmetric erythrokeratoderma
197
Acral Peeling Skin Syndrome
TGM5, AR
198
CHILD
congenital hemidysplasia with ichthyosiform erythroderma and limb defects
NSDHL (3B hydroxysteroid dehydrogenase)
**XLD**
Ipslilateral skeletal hemidysplasia, organ hypoplasia
Histology looks like veruciform xanthoma
199
Condradi-Hunermann-Happle Syndrome
XLD chondrodysplasia punctata
EBP (emopalim binding protein)
Erythroderma with blaskoid scale that resolves and is replaced by follicular atrophoderma
stippled epiphyses
asymmetric skeletal anomalies
200
IFAP
Ichthyosis follicularis atrichia photophobia syndrome
MBTPS2
XLR
erythroderma, scaling, and follicular hyperkeratosis
nutmeg grater scale
201
Diffuse Epidermolytic Palmoplantar Keratoderma (EPPK)
Previously Vorner
Most common Keratin 1, 9
Can also inclue Unna-Thost (? KRT 1,6c)
**AD**
Well-demarcted yellow hue
Not transgradiens apart from the ***Greither*** variant which is over achilles, elbows, knees (KRT1 in families)
**No systemic involvement**
202
SLURP-1
**Mal de Meleda**
secreted Ly6/Plaud domain-containing protein (**AR)**
transgradiens PPK
hyperhidrosis
smelly, superinfected
203
Vohwinkel
Mutilating PPK
GJB-2, connexin 26
**transgradiens**
honeycombed palmar PPK
pseudoainhuma
starfish keratoses
deafness
204
Loricrin Keratoderma
LOR, AD
Like Vohwinkel + ichthyosis
Previously classified as Vohwinkel
205
Papillon-Lefevre
CTSC (Cathepsin C); AR
Transgradiens PPK with peridontitis
Terrible odor
Prematures loss of teeth
dural calcifications
pseudoainhum of elbows and knees
acral melanoma/SCC
206
Naxos
JUP (Plakoglobin); AR
Right ventricular cardiomyopathy
wooly hair
diffuse ppk
non-transgradiens
207
Diffuse PPKs
Vorner/Unna-Thost
Mal De Meleda
Vohwinkle
Greither
Papillon-Lefevere
Naxos
208
Striate PPK
AD
DSG1, desmoplakin, KRT1, KRT 16, KRT 6c
209
Richner-Hanhart
TAT, AR
tyrosinemia type II
focal painful PPK
dendritic keratitis
corneal ulcers
blindness
210
Carvajal
DSP, AR\> AD
Desmoplakin
striate PPK
wooly hair
Left sided cardiomyopathy
hypodontia
nail dystrophy
211
Howel-Evans
Tylosis with Esophageal Cancer
RHBDF2/IRHOM2
AD
Risk of esophageal cancer in 3rd-5th decade
