Genoderm and Peds Derm Flashcards
1
Q
Hyper-IgE syndrome is associated with which mutations (3)? What differentiates the clinical presentation of these 3 mutations?
A
STAT3, DOCK8, Tyk2
- All have eczema, sinopulm infections, elevated IgE
- STAT3 = Job Syndrome; AD with connective tissue, skeletal and vascular abnormalities
- DOCK8: severe cutaneous viral infections (e.g. warts) and premature malignancies
- Tyk2: nontuberculous mycobacterial infections
2
Q
Hidrotic Ectodermal Dysplasia
Eponym?
Gene?
Features?
A
Cloustons Syndrome connexin 30 (gjb6)
Hypotrichosis, nail dystrophy, diffuse PPK, MR
normal teeth and sweating
3
Q
What genodermatoses are associated with a connexin 26 mutation (4)?
A
- KID syndrome
- PPK with deafness
- Volwinkel syndrome
- Bart-Pumphrey
4
Q
Type of EB characterized by herpitiform blisters at birth?
A
EBS, generalized, severe (Dowling-Mera)
5
Q
What is mutated in a child with wooly hair, PPK and right sided cardiomyopathy?
A
plakoglobin = Naxos Syndrome
desmoplakin = Carvajal Syndrome with PPK, Wooly hair and LEFT sided Cardiomyopathy.
Remember: p points to the Right; d points to the left.
6
Q
What are the different clinical features of Ehlers Danlos when the following are mutated: Tenascin X, lysyl hydroxylase (PLOD), type III collagen, type V collagen, pro collagen N-proteinase (ADAMTS2), type I collagen?
A
- Tenascin-X = Hypermobility: joint hyper mobility, minimal skin findings; can have congenital adrenal hyperplasia
- Lysyl hydroxylase = Kyphoscloliosis: respiratory issues, muscle weakness, ocular fragility
- Type III collagen = Vascular: visible veins, vascular fragility, bruising, hypermobility
- Type V collagen = Classic: hyperextensible skin/joints, fish-mouth scars, Gorlin sign (tongue to nose), no frenulum, MVP
- Pro-collagen N-proteinase = Dermatosparaxis: extremely fragile, sagging skin; hernias, easy bruising
- Type 1 collagen = Arthrochalasia: joint hypermobility, dislocation of large joints (congenital hip dislocations), scoliosis, easy bruising
7
Q
What genodermatosis is associated with a mutation in LEMD3? Function of LEMD3? Clinical manifestations?
A
Buschke-Ollendorf syndrome (AD)
LEMD3 encodes a inner nuclear membrane protein
- Elastomas (Dermatofibrosis lenticularis disseminata)
- Osteopoikilosis (bushes in the bone!)
8
Q
What mutation is present in DSAP and Hyper IgD Syndrome?
A
Mevalonate kinase gene (MVK) - may regulate calcium-induced keratinocyte differentiation and may protect from UVA-induced apoptosis
9
Q
Which genodermatoses have trichoepitheliopmas (3)?
A
Brook-Spiegler, Rombo, Bazex
10
Q
Differential diagnosis of trichorrhexis nodosa?
A
“TACK + others” = Trichothiodystrophy and Traumatic hair care; Arginosuccinic aciduria, Citrullinemia (arginocyccinate synthetase defect), Kinky Hair (Menke’s); others = Nethertons, metabolic disorders including zinc and biotinidase deficiency
11
Q
What conditions have defective DNA Helicases (3)?
A
Bloom (RecQL2), Rothmund-Thompson (RecQL4), Werner(adult progeria - WRN gene)
12
Q
What is the differential diagnosis of atrophoderma vermiculatum (honeycomb pattern of atrophic scars on face)?
A
- Tuzun syndrome (+ scrotal tongue)
- Rombo (+ BCC, milia, peripheral vasodilation with cyanosis, trichoeps)
- Nicolau-Balus (+ eruptive syringomas, milia)
- Braun-Falco-Marghescu (+ KP, palmoplantar hyperkeratosis)
- Down syndrome
13
Q
What is the mutation and features of EEC syndrome?
A
EEC = Ectrodactyly (lobster claw deformity) - Ectodermal Dysplasia - Cleft lip/palate
mutation in EEC1, EEC2 or EEC3 - all are P63 (tumor suppressor needed for limb, craniofacial and epidermal morphogenesis).
50% also have sensorineural deafness; 30% have hydronephrosis; can have blond, sparse hair; 70% cleft lip/palate, hypodontia
14
Q
What is the mutation and features of AEC syndrome? Eponym?
A
AEC = Ankyloblepharon (fusion of eyelids with strands of skin) - Ectodermal Dysplasia - Cleft palate
Eponym = Hay-Wells
AD mutation of p63 gene (hererozygous missense mutation in SAM domain).
Erosive scalp dermatitis; sparse hair +/- scarring alopecia; dystrophic/absent nails; lacrimal duct atresia; chronic otitis media that can lead to deafness; can have collodion membrane-like presentation at birth; 80% cleft lip/palate
15
Q
Elastosis Perforans Serpiginosa is associated with which conditions (10)?
A
“MAD PORES” = Marfans, Morphea; Acrogeria; Down Syndrome; Pseudoxanthoma Elasticum; Osteogenesis Imperfecta; Rothmund-Thompson; Ehlers Danlos; Scleroderma and Cutis Laxa
16
Q
Name the gene mutation and protein affected in the 4 types of oculocutaneous albinism
A
OCA1 = TYR (tyrosinase) OCA2 = OCA2 (P gene; also affected in Angelman and Prader-Willi) OCA3 = TYRP1 (transport-related protein 1) OCA4 = MATP (membrane associated transport protein)
17
Q
What is the juvenile counterpart to DFSP? What are key histopathologic findings?
A
Giant Cell Fibroblastoma; multinucleated giant cells lining vascular like spaces
18
Q
Which PPKs have periodontitis as a features?
A
Papillon-Lefevre and Haim-Munk (AR; Cathepsin C mutations in both, which is a lysosomal protease
Haim-Monk is Papillon-Lefevre + onychogryphosis
19
Q
Name 3 causes of transient neonatal pustules. What would smear show (neuts or eos)? Who gets each? Treatment?
A
- Transient Neonatal Pustular Melanosis: present at birth as pustules or “collarettes of scale” in pigmented individuals; smear shows NEUTS. No Tx necessary.
- Erythema Toxicum Neonatorum: 24-48 h after birth; 50% of term babies; rare in preeemies. Smear shows EOS. No Tx - resolves in a couple weeks.
- Neonatal Cephalic Pustulosis (Neonatal Acne): onset first 30 days; due to Malassezia; smear shows NEUTS and yeast.
20
Q
Name 3 conditions associated with asplasia cutis congenita.
A
- Bart Syndrome: ACC of lower extremity + dominant dystrophic epidermolysis bullosa
- Adams-Oliver Syndrome: ACC of scalp with skull ossification defect + extensive CMTC + limb defects + cardiac anomalies
- Seitles Syndrome: bilateral temporal ACC + abnormal eyelashes, upslanting eyebrows + leonine facies
21
Q
What are the diagnostic criteria for Kawasaki disease (need 5 of 6)?
A
- Rash
- Fever x 5 days
- Conjunctivitis (with perilimbic sparing)
- Palmoplantar erythema, edema or desquamation
- Swollen lips or red tongue
- Cervical lymphadenopathy (>/= 1.5 cm)
22
Q
Describe the 3 forms of childhood PRP - clinical features, likelihood of resolution.
A
- Classic Juvenile (III): Resembles classic adult; onset first 2 years of life, resolves within 3 years
- Circumscribed Juvenile (IV): extensor surfaces involved, onset in prepubertal years; 50% persist into adulthood (most common childhood form)
- Atypical Juvenile (V): type III + sclerodermoid changes of hands/feet; familial. Presents in childhood and persists.
23
Q
Which innate antimicrobial peptides are deficient in atopic dermatits?
A
human beta-defencins (HBD)
Canthelicidins (LL37)
24
Q
Name 5 genoderms with lentigines. Mutations? Other features?
A
- LEOPARD = PTPN11 gene (AD); Lentigines, EKG changes, ocular hypertelorism, pulm stenosis, abnormal genitalia, growth retardation, deafness
- Carney complex (LAMB or NAME Syndrome) = PRKAR1A (AD); psammomatous melanotic schwannomas, cardiac/skin myxomas, blue nevi, endocrine overactivity (nodular adrenocortical disease –> Cushings; pituitary GH-secreting tumors; testicular tumors)
- Peutz-Jeghers = STK11 (AD); mucocutaneous lentigines, intestinal polyposis, intussusception, malignancies (GI adenocarcinoma, other solid organs - breast, uterine, cervix, thyroid)
- Laugier-Hunziker Syndrome = mucocutaneous lentigines, longitudinal melanonychia, genital melanosis
- Bannayan-Riley-Ruvalcaba = PTEN (AD); penile > vulvar lentigines, lipomas, hemangiomas, trichilemmomas; risk of breast/thyroid/GI cancers
25
What are the size cutoffs for congenital nevi?
Small < 1.5 cm
Medium 1.5 - 20 cm
Large > 20 cm or 10% BSA
26
What is the most common genetic mutation in Spitz nevi?
Gain of 11p - HRAS gene
27
What features are common of all Junctional Epidermolysis Bullosa variants?
- Enamel Hypoplasia with pits/caries
- Anemia
- Growth retardation
- Recurrent tracheobronchial infections
28
Multiple pilomatricomas are associated with which conditions (5)?
* Myotonic dystrophic with beta-catenin defect
* Rubenstein-Taybi
* Turner
* Gardner
* Sarcoidosis
29
Which 3 adnexal neoplasms are seen in Brooke-Spiegler Syndrome? Mutation? Risk for malignancy?
* Trichoepitheliomas
* Cylindromas
* Spiradenomas
- - Risk of salivary gland tumors
- - Mutation in CYLD gene, which regulates NF-kB
30
What are the histopathologic findings of infantile digital fibromatosis? Stains?
* Interlacing fascicles of fibroblasts/myofibroblasts in collagenous stroma with eosinophilic inclusions
* Inclusions are red with trichrome, purple with PTAH
31
Name the 4 Langerhans Cell Histiocytoses and describe features.
1. Letterer-Siwe: multisytem, onset before 2; skin findings in seborrheic distribution
2. Hand-Schuller-Christian: triad of DI, osteolytic bone lesions, exophthalmos; onset 2-6; eval for systemic disease with CBC, LFTs, skeletal survey
3. Eosinophilic Granuloma: localized to bone (cranium), spontaneous fractures; onset older children
4. Congenital Self-Healing Reticulohistiocytosis (Hashimoto-Pritzker): limited to skin with onset around birth; widespread crusted papules that heal within weeks-months
32
What does PHACES stand for?
```
Posterior fossa malformation (Dandy Walker malformation most common)
Hemangioma
Arterial anomalies
Cardiac defect, Coarctation
Eye abnormalities
Sternal defect, Supraumbilical raphe
```
33
What does LUMBAR stand for (should replace PELVIS because is more complete)?
Lower body hemangioma / Lipomas (lipomyelomeningocele)
Urogenital anomalies
Myelopathy
Bony deformities
Anorectal anomalies (imperforate anus, skin tags)/ Arterial anomalies
Renal anomalies
34
What does POEMS stand for? Other features?
```
Polyneuropathy
Organomegaly
Endocrinopathy
Monoclonal gammopathy (or Castlemans)
Skin lesions
```
* Pathognomonic skin lesion = glomeruloid hemangioma; can also have cherry and lobular angiomas
* Other features: sclerotic bone lesions, papilledema, pleural effusions, peripheral edema, ascites, > 90% have diffuse cutaneous hyperpigmentation
35
Name the X-linked Recessive Genoderms...
"CHAD'S Kinky WIFE, CHANDra"
```
Chronic Granulomatous Disease
Hunter Disease
Anhidrotic Ectodermal Dysplasia
Dyskeratosis Congenita
SCID
```
Menke's Kinky Hair Disease
```
Wiskott-Aldrich Syndrome
Ichthyosis, X-linked
Fairy disease
Ehlers-Danlos (type V and IX)
Chondrodysplasia Punctata (NOT Conradi-Hunerman type)
Hypohidrotic Ectodermal Dysplasia w/ Immunodef
Agammaglobulinemia, Bruton's
Lesch-Nyhan Syndrome
```
36
Name the X-linked Dominant Genoderms..
"BIG ChOMP"
Bazex Syndrome
Incontinentia Pigmenti (Bloch-Sulzberger)
Goltz syndrome
CHILD syndrome
Oro-Facial-Digital Syndrome
MIDAS syndrome (micrognathia, dermal aplasia, sclerocornea)
Chondrodysplasia Punctata (Conradi-Hunermann type)
37
Most types of Xeroderma Pigmentosum are due to defects encoding _________. XP Variant is due to a mutation in __________.
Nucleotide Excision Repair
XP Variant: DNA polymerase; no neuro abnormalities in XP variant
38
Which conditions have mutations in excision repair cross-complementation groups (ERCC)?
* Xeroderma pigmentosum
* Cockayne Syndrome (ERCC6 and ERCC8)
* Trichothiodystrophy or PIBIDS (ERCC2 and ERCC3)
All are AR!
39
Which conditions have mutations in DNA helicases (increased risk of sister chromatid exchanges)? Which cancers are these patients at increased risk of developing?
Bloom Syndrome = RecQL2 (maybe 3); Leukemia, Lymphoma, GI adenocarcinoma
--Bloom patients also have photo distributed telangiectasias, short stature, immune deficiency with decreased IgM and IgA, high-pitched voice
Rothmund-Thompson = RecQL4; Osteosarcoma
-- RT patients also have hypo plastic thumbs, poikiloderma, cataracts, premalignant aural keratoses, alopecia
Both have normal intelligence and hypogonadism.
Werner Syndrome = RecQL2; soft-tissue sarcomas, osteosarcomas, SCCs
-- Adult-onset progeria in 20s; pinched face, beaked nose, mottled hyperpigmentation, sclerodermoid changes, cataracts, DM, atherosclerosis, chronic leg ulcers
40
What is the genetic mutation in Dyskeratosis Congenita (both the XLR and AD forms)? What are common features? Which malignancies are patients at risk for?
Mutations in telomerase function (increased sister chromatid exchanges).
Features: poikiloderma, nail dystrophy, premalignant leukoplakia (buccal mucosa most common), friction bull, palmoplantar hyperhidrosis, MR, epiphoria (continuous lacrimation); BONE MARROW FAILURE
Cancer: mucosal SCC, Hodgkin's lymphoma, AML
TX= bone marrow transplant
41
What are the diagnostic criteria for NF1 (need 2+ of 6)?
6+ CALMs OR 2+ neurofibromas or 1 plexiform NF
-- CALMs > 0.5 cm prepuberty; > 1.5 cm post.
Axillary or inguinal freckling
Optic glioma
2+ Lisch nodules
Sphenoid wing dysplasia or thinning cortex of long bone
1st degree relative with NF
42
What are the mutations, skin findings and malignancy risks of the Multiple Endocrine Neoplasia Syndromes?
MEN1: MEN1 mutation (menin a tumor suppressor)
- - Findings: angiofibromas, collagenomas, lipomas, CALMs
- - Cancers: Pituitary, Parathyroid, Pancreatic (3Ps)
MEN2a/Sipple: RET mutation (tyrosine kinase receptor)
- - Findings: lichen/macular amyloidosis, hemangiomas, genital lentigines, hamartomas, lipomas
- - Cancer: Parathyroid, Pheo, Thyroid medullary carcinoma (2Ps + thyroid)
MEN2b: RET mutation
- - Findings: Marfanoid habitus, mucosal neuromas, thick lips
- - Cancer: Pheo, thyroid medullary carcinoma, diffuse ganglioneuromatosis (megacolon)
43
Which skin growths and malignancies are associated with Birt-Hogg-Dube Syndrome?
Skin: fibrofolliculomas, trichodiscomas, acrochordons, lipomas
Malignangies: clear cell renal cell carcinoma, medullary carcinoma of thyroid
Mutation = FLCN, encodes folliculin
Other: spontaneous pneumothorax!
44
What does APECED stand for, what is mutated and what are features of this condition?
APECED = Autoimmune Polyendocrinopathy - Candidiasic - Ectodermal Dysplasia
Mutation = AIRE gene (autoimmune regulator)
Findings: thyroid/parathyroid abnormalities, DM, hypoadrenocorticism, alopecia areata, vitiligo, pernicious anemia, seb-derm like rash, infections, chronic diarrhea, failure to thrive
45
What are the mutations and features of the 4 types of Waardenburg Syndrome?
Type 1: PAX3 = white forelock, leukoderma, heterochromia iris, synorphrys, dystopia canthorum; not typically deaf
Type 2: MITF = Type 1 but DEAF; no dystopia canthorum
Type 3: PAX3 = Type 1 + upper limb abnormalities (hypoplasia, syndactyly, flexion contractures)
Type 4: SOX10: Type 1 + Hirschprung dsiease, deafness common
-- EDN3 (endothelin-3) and EDNRB (endothelin receptor) cause phenotype similar to type 4; are AR (all other WS are AD)
46
X-linked ichthyosis
Gene?
Presentation at birth?
What differentiated X-linked ichythosis from Lammellar Ichthyosis?
steroid sulfatase (XLR)
- Presents with mild erythroderma and large translucent scales
- Evolves into adherent brown (dirty) scales on the extremities, trunk and neck. Spares palms/soles and face.
Lamellar ichthyosis presents with a collodion membrane and involves with face!
47
Epidermolytic Ichthyosis
Gene? What are the two different presentations associted with the genes?
Presentation at birth?
Characteristic feature?
Keratin 1 and 10 (AD)
K1 has severe PPK. K10 spares the palms and soles
- Presents with erythroderma, bullae and denuded skin
- Evolves into verrucous hyperkeratotic plaques and PPK
-Pungent body odor!
48
Lamellar Ichthyosis
Gene? Function?
Presentation at Birth?
Other associated features?
Transglutaminase 1 catalyzes the calcium dependent cross-linking of proteins in the cornified cell envelope
also mutations in ABCA12 (harlequin ichthyosis) have been reported
Presents as collodion baby
Evolves to thick, dark scale with prominent flexural involvement
Also has ectropion, eclabium, alopecia, heat intolerance
49
What disorders can present as a Collodion Baby? (8)
Inheritance?
Autosomal Recessive
```
Self-healing collodion Baby
Lamellar ichthyosis
Congenital Ichthyosiform Erythroderma
Sjogren-Larssen
Gaucher Disease
Trichothiodystrophy
Neutral Lipid Storage Disease (Very rare)
Conradi-Humermann-Happle Syndrome (very rare)
```
Also some ectodermal dysplasias can rarely present as a collodion baby
50
Lamellar Ichthyosis
Gene? Function?
Presentation at Birth?
Other associated features?
Transglutaminase 1 catalyzes the calcium dependent cross-linking of proteins in the cornified cell envelope
also mutations in ABCA12 (harlequin ichthyosis) have been reported
Presents as collodion baby
Evolves to thick, dark scale with prominent flexural involvement
Also has ectropion, eclabium, heat intolerance
51
Congential Ichthyosiform Erythroderma
Genes (5)?
Presentation at birth?
TGM1, ALOXE3, ALOX12B, NIPAL4 (ichthyin) & ABCA12
ALOX genes are synthesized in the epidermis and generate epoxy alcohol metabolites crucial for formation of the epidermal lipid barrier
presents with a collodion membrane
Evolves to generalized erythroderma and scaling
52
Netherton's syndrome
Gene?
Presentation at birth?
Characteristic feature on the skin?
Hair abnormalities?
SPINK5 (AR)
Presents with generalized erythroderma and scaling
Ichthyosis linearis circumflexa
trichorrhexis invaginata, trichorrhexis nodosoa, pili torti
elevated IgE
53
Sjogren-Larsson Syndrome
Gene? Function?
Presentation at Birth?
Pathognomonic finding?
Other Extracutaneous findings?
Fatty aldehyde dehydrogenase gene (FALDH/ALDH3A2)(AR)
catalyzes the NAD dependent oxidation of long chain aldehydes into fatty acids. Important for epidermal lipids and also phospholipids and sphingolipids in the brain. symptoms from accumulation of fatty acids
Presents with erythroderma, hyperkeratosis and scaling (varying degree). Rarely presents as a collodion baby.
Evolves to hyperkeratosis and scaling + PPK
Perifoveal glistening white dots in the ocular fundus (juvenile macular dystrophy)
delayed motor development, abnormal gait, pyramidal signs, spasticity and contractures (presents around year 1)
Progressive speech defect and diplegia (or tetraplegia)
54
Linear earlobe crease, facial vascular malformations and macroglossia + exophthalmos = ______________
Mutation? Cancer risk?
Beckwith-Wiedemann Syndrome (exophthalmos-macroglossia-gigantism)
KIP2 gene mutation (inhibits G1 cyclin, which is a regulator of cell proliferation); inherited AD but most cases spontaneous
Cancer: Wilms tumor, hepatoblastoma
55
What are the features of Rubenstein-Taybi Syndrome? Mutation?
Features: vascular malformations, spindle cell hemangioma, broad thumbs, beaked nose, MR, congenital heart defects, cryptorchidism, eruptive keloids, pilomatricomas
Mutations: CREB binding protein (sporadic)
56
What is Parkes-Weber Syndrome?
Fast flow vascular malformation syndrome with limb overgrowth due to AV fistulae. Lytic bone lesions and heart failure can develop; poor prognosis after puberty.
*Fast flow differentiates this from Klippel-Trenaunay which has capillary/venous malformations
57
The following tooth findings are characteristic in which conditions?
- - Enamel Pits
- - Peg Teeth (2)
- - Anodontia (2)
- - Odontogenic cysts
- - Retention of Primary teeth
Enamel pits = Tuberous sclerosis
Peg Teeth = Incontinentia Pigmenti, Anhidrotic Ectodermal Dysplasia
Anodondia = Hypomelanosis of Ito, IP
Odontogenic cysts = Gorlin Syndrome
Retention of Primary Teeth = Job Syndrome
58
HHT1 (endoglin) and HHT2 (ALK1) can be mutated in hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu). What differentiates these mutations?
HHT1 = increased risk of pulmonary and cerebral AVMs
HHT2 = increased risk of hepatic AVMs
4 diagnostic criteria: Epistaxis, Telangiectasias, Visceral lesions, family history
59
What are 3 possible genetic mutations in cutis laxa?
Fibulin 5 (FBLN5)
Elastin
ATP7A (same as Menke's)
60
Name the 3 types of congenital lipodystrophies, mutations and clinical features.
1. Berardinelli-Seip Congenital Lipodystrophy: BSCL2 gene (nuclear laminin); generalized lipodystrophy, insulin-resistant DM, acanthosis nigricans, HSM, umbilical hernias, female hirsutism and infertility; die of hypertrophic cardiomyopathy in 30s
2. Familial Partial Lipodystrophy (Dunnigan): LMNA gene; symmetric lipodystrophy of trunk/limbs, tuberoeruptive xanthomas, acanthosis nigricans
3. PPARG gene, males more than females; trunk spared; more severe metabolic issues
61
Key cutaneous finding of Buschke-Ollendorf? Key bone finding? Mutation?
Dermatofibrosis lenticularis disseminata = juvenile elastoma
X-ray: Osteopoikilosis
Mutation: LEMD3 (inner nuclear membrane)
62
2 conditions with FGFR2 mutations?
Apert Syndrome - severe acne (add more details)
Beare-Stevenson Cutis Gyrata Syndrome: cutis gyrata, acanthosis, anogenital anomalies, craniosynostosis, furrowed palms/soles, skin tags, prominent umbilical stump
63
What lab test should be ordered in a patient with triangular lunulae and posterior iliac horns? Mutation? Other findings? Names for this condition?
Urinalysis to evaluate for glomerulonephritis.
Mutation: LMX1B ("it hurts to lose your patella so put LMX on it")
Findings: Triangular lunulae, micronychia/anychia, longitudinal fissures; nail findings are worst on thumb and improve as you move to 5th fingers. Absent/hypoplastic patellas, hyper pigmented margin of iris, radial head subluxation.
Names: Nail-Patella Syndrome or HOOD Syndrome (Hereditary Osteoonychodysplasia)
64
Both types of Pachyonychia Congenita have ______. How do the conditions differ?
Both have PPK and dystrophic nails.
Type I (Jadassohn-Lewandrowsky) has benign oral leukokeratosis; K6a/16
Type II (Jackson-Lawler) has steatocystomas, epidermal cysts, natal teeth; K6b/17
65
Which form of ichthyosis is associated with collodion membrane at birth and development of thick, dark scale, ectropion and eclabium? What mutations can cause this condition?
Lamellar Ichthyosis (aka nonbullous congenital ichthyosiform erythroderma)
* AR
* Mutations: TGM1, ABCA12, NIPAL4
Other features: prominent flexural involvement, no improvement with age, PPK, heat intolerance, hypernatremia
Congenital Ichthyosiform Erythroderma: has more fine white/grey scale compared with LI but other findings similar. Mutations = TGM1, ALOXE3 (lipoxygenase 3) or ALOX12B (12R-lipoxygenase)
66
Collodion Baby Differential Diagnosis...(8)
```
Lamellar Ichthyosis (transglutaminase)
Non-bullous CIE (lipoxygenases)
Sjogren-Larsson (fatty aldehydr dehydrogenase)
Gaucher type 2
Trichothiodystrophy
Self-healing collodion baby
Neutral lipid storage disease (ABHD5 gene)
Harlequin fetus
```
67
What would a biopsy from a patient with ichthyosis vulgaris look like?
Absent granular layer, retention hyperkeratosis
Mutation = profilaggrin
-- Filaggrin promotes aggregation and disulfide bonding of keratin filaments
68
Sjogren-Larsson... mutation? skin findings? other characteristic features?
Mutation = FALDH (fatty aldehyde dehydrogenase) - involved in synthesis of epidermal lipids and catabolism of lipids in brain
Skin: erythema at birth --> ichthyosis with dark scales on abdomen, flexures, neck; PPK
Other: perifoveal glistening white dots; spastic ditetraplegia with spastic gait, MR
69
Which ichthyosis looks like corrugated cardboard? Mutation? path findings?
Epidermolytic hyperkeratosis (EHK or Bullous CIE)
Mutation: Keratin 1 and 10
Presentation: erythroderma at birth --> bullae/denuded skin --> verrucous hyperkeratosis, PPK, flexures prominent
Path: massive orthokeratosis, hypergranulosis, cytolysis of suprabasal/granular layers; clumped tonofilaments (keratins)
70
In which conditions do you see verruciform xanthomas?
```
CHILD syndrome (NSDHL gene - enzymes 3b-hydroxysteroid-dehydrogenase)
Lymphedema
Epidermolysis bullosa
pemphigus
DLE
GVHD
```
71
KID Syndrome:
Skin features?
Other features?
Mutation: connexin 26
Skin: erythematous hyperkeratotic plaques on knees, elbows, face; grainy/stippled PPK; risk of SCC; tooth/nail anomalies
Other: sensorineural deafness, vascularizing keratitis --> blindness, photophobia
72
Refsum disease:
- Mutations
- Clinical Features
- Treatment
Mutation: PEX7 (biogenesis factor 7) or PAHX (peroxisomal phytanolyl-CoA hydroxylase) --> excess phytanic acid
Skin: ichthyosis vulgaris-like ichthyosis in childhood
Others: cerebellar ataxia, retinitis pigmentosa ("salt and pepper"; form of night blindness), deafness, heart block
Treatment: dietary restriction of phytanic acid
Memory tool: "REFs wear Black and White (salt and pepper) , often seem DEAF, and break up PHYTs"
73
Darier Disease:
- Mutation
- Nail/Oral findings
- Pathology
Mutation: ATP2A2 gene (encodes SERCA2 = sarcoendoplasmic reticulum calcium ATPase)
Nails: longitudinal erythronychia, red/white alternating longitudinal bands, V-shaped nicks, subungual hyperkeratosis
Mouth: cobblestoning (anal mucosa too)
Path: Acantholysis with cord ronds and grains
74
Mal de Meleda:
- Mutation
- Inheritance
- Features
SLURP-1 gene (secreted Ly-6/uPar related protein)
AR
Features: transgredient PPK (hands/feet/knees/elbows), hyperhidrosis, stinky, perioral erythema, koilonychia
75
Difference between Vohwinkel and Vohwinkel variant?
Vohwinkel: mutilating keratoderma + deafness, connexin 26 mutation, honeycomb-like PPK, starfish keratoses, pseudoainhum (autoamputation of digits), scarring alopecia
Vohwinkel Variant: Mutilating keratoderma + ichthyosis; Loricrin mutation; similar to classic variety but NO deafness and MORE ichthyosis
76
Difference between Papillon-Lefevre and Haim-Munk Syndromes?
Both PPK + Periodontitis
Both Cathepsin C mutation (lysosomal protease); both AR
Papillon-Lefevre: calcification of fall/tentorium, hyperhidrosis
Haim-Monk: Onychogryphosis, arachnodactyly, acroosteolysis
77
Difference between Naxos and Carvajal?
Both PPK + Wooly Hair + Cardiomyopathy; both AR
Naxos: plakoglobin defect (p points right); RIGHT ventricular cardiomyopathy in late puberty
Carvajal: desmoplakin defect (d points left); LEFT ventricle cardiomyopathy in 1st year of life
78
Olmsted Syndrome
- What is it?
- Mutation
Mutilating PPK + periorificial plaques; can develop flexion deformities, autoamputation, SCCs in areas of keratoderma
Mutation: ? maybe K5/14 or TRPV3 (gain of function in chrom 17)
79
Richner-Hanhart Syndrome
- What is it?
- Mutation
- Treatment?
Painful erosive PPK + painful pseudoherpetic keratitis --> blindness; pigmentary dilution of hair
Mutation: AR, tyrosine aminotransferase --> decreased hepatic AST and accumulation of tyrosine in tissues
Treatment: diet low in tyrosine and phenylalanine
80
Schopf-Shultz-Passarge Syndrome
- Features? Common growths?
- Mutation?
PPK + hypodontia + hypotrichosis + onychodystrophy
Growths: apocrine hydrocystomas (eyelids), syringofibroadenomas
Mutation: AR; WNT10A
81
Punctate PPK is associated with... (3)
Darier
Cowden
African descent
82
What is tylosis?
Which form of tylosis has an increased risk of esophageal cancer?
Tylosis = focal, non-epidermolytic PPK
Howel-Evans Syndrome has increased risk of esophageal cancer, PPK over pressure areas and oral leukokeratosis
83
Erythrokeratoderma Variabilis
- - Other name?
- - Mutation?
- - Features?
Mendes de Costa
Mutation: connexin 30.3 and 31 (GJB3 and 4)
Features: erythematous migratory patches, fixed hyperkertotic plaques, 50% have PPK
84
Compare/Contrast hidrotic vs anhidrotic ectodermal dysplasia
- Other names?
- Mutations
- Clinical features especially whether nails/teeth involved
Hidtrotic Ectodermal Dysplasia
- - Clouston Syndrome
- - Connexin 30 (GJB6)
- - hypotrichosis, diffuse PPK, dystrophic nails, MR, eye anomalies; NORMAL teeth/sweating
Anhidrotic Ectodermal Dysplasia
- - Christ-Siemens-Touraine
- - Ectodysplasin A (XLR - part of TNF family) or Ectodysplasin A receptor (AD or AR)
- - hypotrichosis, periorbital hyperpigmentation, NO sweat, NO/CONICAL teeth, thick lips, saddle nose, bronchopulm infections; NORMAL nails.
- - Can have absent/hypoplastic nipple. If Bx necessary to confirm diagnosis, biopsy palm/sole to show no eccrine units
85
What is the mutation for hidrotic ectodermal dysplasia with immunodeficiency?
NEMO / NFkB
XLR inheritance
86
2+ of the following raise concern for spinal dysraphism (9)
```
Hypertrichosis
Tails/pseudotails
Hemangiomas
Dimpling
Lipomas
Dermoid cysts/sinuses
Skin tags
Aplasia cutis
Telangiectasias / capillary malformation / nevi (less likely)
```
87
What are features of GATA2 deficiency?
-- What is GATA 2?
GATA2 = zinc finger transcription factor that regulates vascular development, lymphatics and hematopoietic differentiation
Features: around age 20 develop immunodeficiency with recurrent infections, sensorineural hearing loss, lymphedema. Many people develop myelodysplastic syndrome/leukemia --> stem cell Tx can cure
Skin: recalcitrant warts, soft tissue infections, SCC, erythema nodosum, Sweets, lymphedema
88
Differential Diagnosis of Firm Facial Papules.
Disease and skin findings
Birt-Hogg-Dube (fibrofolliculomas)
Cowdens (trichilemoma)
Brooke-Spiegler (trichopeitheliomas, cylindromas)
Tuber Sclerosis (angiofibroma)
MEN1 (angiofibroma)
Nuerofibromatosis (neurofibroma)
Basaloid Follicular harmartoma (BFH syndrome)
89
Cloves Syndrome
What does it stand for? Gene?
```
Congential
Lipomatous
Overgrowth
Vascular malformations
Epidermal Nevi
Skeletal anomalies (scoliosis)
```
PIK3CA
90
Differential diagnosis of Angiokeratoma Corporis Diffusum (8)
```
aspartylglycosaminuria
glactosialidosis
GM1 gangliosidosis
Fabry Disease
Fucosidase
Kanzaki disease
beta-mannosidosis
sialidosis
```
91
What are three conditions with clinodactyly?
Cornelia de Lange
Russell-Silver syndrome
Down's syndrome
92
What are the main features (7), mutations (2), malignancy risks (3) and treatment for dyskeratosis congenital?
Features: poikiloderma, nail dystrophy, premalignant leukoplakia (buccal mucosa), palmoplantar hyperhidrosis, MR, epiphoria, bone marrow failure
Mutations: Dyskerin (DKC1 gene; XLR); human telomerase RNA component (hTR; AD)
Malignancies: mucosal SCC, Hodgkin's lymphoma, AML
Treatment: bone marrow transplant
93
What are the 5 Classifications of Aplasia Cutis Congenita?
Solitary
Scalp with limb anomalies (Adams-Oliver)
Scalp with epidermal or sebaceous nevi
Scalp with "Hair Collar" Sign -- CNS and other embryologic malformations
Fetus papyraceous or placental infarct (truncal stellate pattern)
94
Name the genodermatoses with photosensitivity and their defects.
```
Nucleotide excision repair defects
- Xeroderma Pigmentosum (XP A - G)
- Trichothiodystrophy (XPB or XPD)
- Cockayne syndrome (ERCC6 and 8)
Chromosome Instability
- Bloom (RecQL3)
- Rothmund-Thompson (RecQL4)
ALso Kindler Syndrome (KIND1)
```
95
What is ulerythema ophryogenes? With which conditions is it associated (4)?
Keratosis pilaris atrophicans faciei --> scarring alopecia of lateral third of eyebrows.
Typically sporadic but associated with Noonan, cardio-facial-cutaneous syndrome, Cornelia de Lange, Rubinstein-Taybi syndromes.
96
Which dermatologic diseases are associated with Wilms tumor (3)?
Beckwith-Wiedemann, Bloom and Macrocephaly-Capillary Malformation syndromes
