Genoderms Flashcards
1
Q
XP - inheritance, gene, clinical findings
A
AR XPA-XPG (nucleotide excision repair) XP-C most common photosensitivity skin cancers solar lentigos (age 2) eye (keratitis, corneal opacification, vascularization) progressive deafness (neuro) 10-20% inc r/o internal malignancy
2
Q
XP variant
A
AR
DNA polymerase ( post replication repair)
same as XP but no neuro sx (no deafness)
3
Q
DeSanctis-Cacchione syndrome
A
AR
usually XPA (form of XP)
term for severe neurologic abnormalities in XP- MR, deafness, ataxia
4
Q
XP genes
A
A = assemble B and D - helicases, bubble the DNA and unwind it C and E = see the damage F = Five prime end G = 3 prime end
5
Q
Cockayne Syndrome
A
AR CS-A (ERCC8) or CS-B (ERCC6) defective transcription coupled excision repair unable to repair cyclobutane pyrimidine dimer products photosensitivity MR cachectic dwarfism peripheral neuropathy sunken eyes prominent ears salt and pepper retinitis pigmentosa dental caries thinning hair basal ganglia calcification progressive deafness, ataxia, spasticity butterfly rash advanced aging with atherosclerosis die 2/2 atherosclerotic dz or neurologic deterioration no increased r/o skin malignancy
6
Q
cockayne -XP overlap gene
A
XP-B,D,G (G most common)
“BiG Deal”
no increased r/o skin cancer but develop pigment abnormalities
7
Q
Aicardi-Goutieres syndrome
A
AR TREX1, RNASEH2A-2C, SAMHD1 nl at birth PERNIOSIS - severe, remember Mancinis case encephalopathy with progressive deterioration (spasticity, dystonia) vision problems joint stiffness mouth ulcers
8
Q
trichothiodystrophy (PIBIDS, Tay Syndrome)
A
AR ERCC2 (XPD) and ERCC3 (XPB) defect in nucleotide excision repair sulfur (cysteine) deficiency in hair Photosensitivity Ichthyosis (can be collodion) Brittle hair (tiger tail (polarized light), flattened hair shafts like ribbons) Intellectual impairment Decreased fertility Short stature receding chin, protruding ears, nail dystrophy liver angioendotheliomas no inc r/o skin cancer
9
Q
bloom syndrome (congenital telangiectatic erythema)
A
AR
BLM gene
RecQL2 (RecQL3 per Spitz and Galderma)
DNA helicase, inc sister chromatid exchange
butterfly erythema/telangiecatasia w/i first few weeks of life
short stature
nl intelligence
immune def (low IgM, igA +/- IgG)
dec fertility
high pitched voice
elfish facies
r/o lymphoma, leukemia, Wilms tumor (most common solid organ) GI adenocarcinoma
“little girl exchanging flowers with sick infertile sister”
10
Q
rothmund-thompson (poikiloderma congenitale)
A
AR RecQL4 DNA helicase photo distributed erythema and vesicles first few months of life poikiloderma and ext to buttocks and extremities (trunk spared) premalignant acral keratoses (teenager) cataracts hypoplastic thumbs/radii/ulnae hypotrichosis, nail and dental abn saddle nose deformity pituitary hypogonadism nl intelligence inc r/o SCC, melanoma, osteosarcoma
11
Q
dyskeratosis congenita (zinsser-Engman-Cole syndrome)
A
XLR - DKC1 (protein dyskerin) (most common overall) - interacts with telomerase, inc sister chromatid exchange
AD - TINF2 (most common AD), hTR or hTERT
*reticulate poikiloderma (face, trunk, thighs)
*nail dystrophy (pterygium, atrophy)
premalignant leukoplakia (buccal > tongue)
friction bullae
PPK and hyperhidrosis
BM fx with anemia, low plt, or pancytopenia (mortality)
inc r/o mucosal SCC, Hodgkins lymphoma, AML
12
Q
ataxia telangiectasia (Louis Bar Syndrome)
A
AR
ATM gene (responds to DNA damage by phosphorylating key substrates involved in DNA repair- mut reduces ability to repair chromo strand breaks)
sens to ionizing radiation
ataxia - 2-3 yr old
telangiectasia - 3-5 yr old - bulbar conjunctiva, cheeks, ears
premature aging (atrophic/sclerotic face)
dec purkinje fibers in cerebellum
segmental hyper or hypopigmentation
noninfectious cutaneous granulomas (BM kodachrome, common, can be ulcerated)
defect in cellular and humoral immunity (low IgA, IgG, IgE)
sev and freq simopulm infxn
inc r/o lymphoreticular malig, breast ca
bronchiectasis with resp fx most common cause of death
13
Q
Fanconi syndrome
A
AR
chromosomal breakage
diffuse hyper pigmentation with hypopig macules within
CALMs
pancytopenia
hypoplasia or radius and thumb
inc SCC, solid organ ca (neuroepithelial tumors ie medullobalstoma may be presenting sx) luekemia
14
Q
basal cell nevus syndrome (gorlin syndrome)
A
AD PTCH (mutant PTCH allows hedgehog binding and removes PTCH repression of SMO which leads to act of Gli which leads to BCC) BCCs - may look more like nevi pp pits (look like red macules) odontogenic cysts of jaw frontal bossing, hypertelorism cataracts, glaucoma bifids ribs, calc of falx cerebrum a genesis of corpus callosum r/o medulloblastoma, ovarian fibromas, meningioma
15
Q
NF-1 (Von Recklinghausen dz)
A
AD
NF-1 gene (encodes neurofibromin - negatively regulates RAS, tumor suppressor protein)
criteria:
1. CALMs >5 and >0.5cm in kids, > 1.5cm in teenagers
2. 2 neurofibromas or 1 plexiform neurofibroma
3. axillary or inguinal freckling (crowe’s sign)
4. optic gliomas
5. lisch nodules (iris)
6. sphenoid wing dysplasia, cortical thinning of long bones (bowed legs)
7. first degree relative
r/o malignant peripheral nerve sheath tumor, neurosarcoma, JMML (esp if JXG present), rhabdomyosarcoma
HTN, MR, sz, kyphoscoliosis, endocrine dz
16
Q
Legius Syndrome
A
SPRED1
CALMs and axillary/inguinal freckling
“spread your legs”
17
Q
NF-2 (bilateral acoustic neurofibromas)
A
AD NF-2 gene (merlin/schwannomin) criteria: 1. bilateral CN VIII masses OR 2. first deg relative AND unilateral CN VIII mass or 2 of following: cutaneous schwannoma optic glioma meningioma juvenile posterior subcapsular opacity (cataract)
18
Q
Carney Syndrome (NAME or LAMB)
A
AD
PRKAR1A gene
can be considered in the family with MEN
*ephelides (peripubertal, lips, oral mucosa, conjunctiva)
*epithelioid blue nevi
cafe au lait macules
cutaneous myxomas (eyelids, genitals, nipples, ears)
atrial myxomas
*psammomatous melanotic schwannoma
primary pigmented adrenocortical disease (Cushings)
tumors: testicular, pit GH secreting tumors, ovarian tumors
19
Q
muir torre syndrome
A
AD MLH1, MSH2, MSH6 DNA mismatch repair genes - leads to microsatellite instability loss of heterozygosity leads to tumors sebaceous neoplasms keratoacanthomas inc r/o colon cancer, less common GU, lung, breast or heme variant of lynch (HNPCC)
20
Q
tuberous sclerosis ( bourneville syn)
A
AD TSC1 (hamartin) and TSC2 (tuberin) tumors suppressors that regulate GTPase of rap1GAP family ash leaf macules, thumb print macules, confetti macules (earliest sign) facial angiofibromas (adenoma sebaceum) connective tissue nevi (shagreen patch) - us LS area fibrous forehead plaque fibromas (gingival and subungual) CALMs dental enamel pits sx findings: renal angiomyolipomas (renal cysts with TSC2 contiguous with PCKD) retinal hamartomas sz pulmonary lymphangiolieomyomatosis, cortical tubers cardiac rhabdomyoma
21
Q
cowden syndrome (multiple hamartoma syndrome)
A
AD PTEN (tyrosine phosphatase prot, mut causes cell proliferation) KILLIN (methylation) AKT1 PIK3CA trichilemommas cobblestone mucosa (oral papillomas) acral keratotic papules sclerotic fibroma thyroid (follicular, second most common), breast (most common), breast fibroadenoma, colon polyps
22
Q
Lhermitte-Duclos
A
PTEN mutation
rare slow growing tumor in the cerebellum
Assoc with cowdens and can have same manifestations and r/o cancer as Cowdens
23
Q
Bannayan Riley Ruvalcaba (bannayan-Zonana)
A
AD PTEN *genital lentigines hamartomas lipomas hemangiomas can have facial trichilemommas, oral papillomas just like Cowdens MR, *macrocephaly very similar to Cowdens, may be a variation of this syndrome
24
Q
CLOVES
A
PIK3CA
Congenital Lipomatous Overgrowth with Vascular, Epidermal and Skeletal abnormalities
on differential for large PSW and macrocephaly
kind of looks like proteus because there is a lot of overgrowth
25
MEN1 (wermer syndrome)
```
AD
MEN1 mutation = menin protein (tumor suppressor)
*CALMs
angiofibromas, collagenomas, lipomas
pituitary
parathyroid
pancreas
```
26
MEN2A (sipple syndrome)
```
AD
RET mutation (tyrosine kinase receptor)
parathyroid
medullary thyroid (2=T)
pheochromocytoma
*lichen or macular amyloidosis
hemangiomas, genital lentigines, hamartomas, lipomas
```
27
MEN2B (multiple mucosal neuroma syn)
```
AD
RET mutation (tyr kinase receptor)
mucosal neuromas (tongue, lips, conjunctiva, eyelids)
thickened lips
medullary thyroid (2=T)
pheochromocytoma
marfanoid habitus
diffuse ganglioneuromatosis (megacolon, diarrhea)
```
28
LEOPARD syndrome (multiple lentigines syndrome)
AD
PTPN11 gene (same gene as Noonan), 3% RAF1
Shp2 protein (tyrosine phosphatase)
*lentigines (4-5yo per Hurwitz - genitalia, hands, feet)
*CALMs
*EKG abnormalities (most common hypertrophic CM 75%)
Ocular hypertelorism
pulmonic stenosis
abnormal genitalia
retarded growth
deafness
29
Peutz- Jeghers
AD
STK11/LKB1 gene - serine-threonine kinase tumor suppressor
mucosal lentigines (also fingers, infancy but fade with age)
intestinal polyposis (bleeding, intussusception, starts around 8-10yo)
GI adenocarcinoma, other solid tumors (breast, uterine, sex tumors)
30
Laugier–Hunziker syndrome
macular hyperpigmentation of the lips and buccal mucosa
melanonychia striata
no visceral manifestations, no cancer risk
31
Gardner syndrome
AD
APC gene (tumor suppressor gene - ras proto-oncogene)
form of familial adenomatous polyposis (FAP)
*epidermoid cysts
*pilomatricomas
osteomas (mandible, maxilla)
supernumerary teeth
odontomas
fibromas
CHRPE (congenital hypertrophy of the retinal pigment epithelium)
*GI adeno (inevitable), osteochondromas, thryoid papillary ca, hepatoblastoma, adrenal adenomas
32
Birt-Hogg-Dube
```
AD
BHD gene encodes follicular
fobrofolliculomas
trichodiscomas
acrochordons (face, neck, scalp, trunk)
angiofibromas (similar to TS but develop later)
renal cell carcinoma
medullary thyroid ca
spontaneous pneumothorax (pulm cysts) "smokin a dube"
```
33
dysplastic nevus syndrome
```
AD
CDKN2A (p16 tumor suppressor gene, inh cyclin dep kinase 4)
dysplastic nevi
melanoma
pancreatic cancer
astrocytoma
```
34
Werner syndrome (adult progreria)
```
AR
RECQL2 gene (WRN gene) encodes RECQ DNA helicase - genomic instability
subset with LMNA mutation - accelerated aging but no DM or cataracts
nl growth - 2nd decade:
short stature/thin limbs
gray hair
central obesity
*pinched facial expression - beaked nose, micrognathia
high pitched voice
mottled hyperpigmentation
*sclerodermoid changes
cataracts
DM
*atherosclerosis
*chronic leg ulcers
osteoporosis
hypogonadism
tumors: soft tissue sarcomas, osteosarcomas, SCCs
japanese - melanoma, thyroid ca
```
35
Progeria (Hutchinson-Gilford Syndrome)
```
AD
LMNA gene encodes lamin A and lamin C - nuclear envelope proteins (scaffolding of the nucleus)
premature aging (median life span 12)
large cranium
frontal bossing
prominent scalp veins
micrognathia
plucked bird appearance
loss of SQ
sclerodermoid changes
alopecia
high pitched voice
avg intelligence
severe atherosclerosis
new treatment: protein farnesyltransferase inn = Lonafarnib
```
36
Familial Chronic Mucocutaneous Candidiasis
recurrent progressive candidiasis - skin, nails, mucosa
can look ichthyotic
assoc with APECED and endocrinopathies
they do not get systemic candidiasis
37
hyperIgE syndrome (Job syndrome)
```
AD - STAT3
AR - TYK2
inc IgE levels
peripheral eosinophilia
cold abscesses
coarse facies (deep set eyes, broad nasal bridge, wide fleshy nasal tip, mild prognathism)
eczematous dermatitis
lung abscesses, pna, pneumatocele
retained primary teeth
otitis media
osteopenia with fractures
```
38
restrictive dermopathy
ZMPSTE24 mut or LMNA mut
inability to process lamin A and build up of prolamin A which is nuclear membrane toxic
die of restrictive lung disease immediately or within months of delivery
39
Wiskott-Aldrich
XLR
WASP gene (WAS protein - involved in actin filament assembly)
Infection due to abn humoral and cell mediated immunity ( low IgM)
Platelet dysfunction and low plt (petechiae, bruising, hematuria, hematochezia)
Eczema
"WIPE"
hepatosplenomegaly, LAD
r/o NHL
death from infxn>hemorrhage > cancer
tx: BMT
40
SCID
XLR - IL2 receptor gamma chain (IL2RG)
AR - JAK2 or adenosine deaminase
severe humoral and cellular immunity
def or total abs of lymphocytes
41
APECED (autoimmune polyendocrinopathy - candidiasis - ectodermal dystrophy)
```
AR
AIRE gene (autoimmune regulatory gene)
3 major criteria:
hypoparathyroidism
addison's
chronic candidiasis
can also have:
thyroid dz
DM
alopecia areata
vitiligo
pernicious anemia
chronic diarrhea, FTT
cut findings: seb derm like, morbilliform, dental enamel abn, nail dystrophy
```
42
OCA Type 1a
```
Tyrosinase negative
AR
TYR gene (tyrosinase enzyme def)
no melanin in skin, hair, eyes (may turn slightly yellow over time)
blue-gray eyes
amelanotic nevi (pink)
extreme UV sens
inc skin ca
photophobia, nystagmus, strabismus, dec acuity (optic fibers get rerouted = monoocular vision)
```
43
OCA Type 1b
```
yellow mutant
AR
TYR gene - decreased activity
little or no pigment at birth but develop some pigment over time - often acral, can be temp sensitive and have more pigment at cooler sites (acral, like a siamese cat)
milder eye findings than type 1a
```
44
OCA Type 2
```
most common
AR
P gene ( dec eumalenin synthesis, defective melanosome biogenesis/processing/transport of TYR and TYRP-1)
mild to modest pigment dilution
pigmented nevi develop over time
light brown hair/skin
same mut as Angelman's and Prader Willi
```
45
OCA Type 3
```
rufous type
AR
TYRP-1 (tyrosinase related protein) - catalyzes the oxidation of 5, 6-dihydroxyindole-2-carboxylic acid monomers into melanin and also stabilizes tyrosinase
light brown or red hair/skin
blue or brown irides
nystagmus, dec acuity
```
46
OCA Type 4
MATP - melanosome membrane transporter
white/japanese (rare)
looks like OCA2
47
Chediak Higashi
AR
LYST/CHS1 gene (lysosomal trafficking regulator)
Large granules (melanocytes, leukocytes, plt, neurons)
Leukopenia
Light pigmentation (OCA with eye sx but nl acuity)
Light sensitivity
Lymphoma
6 L's
immune def
silvery metallic hair with small and evenly spaced clumps of melanin
slate gray skin color - acral sun-exposed (ears, nose) hyper pigmented
inflam and ulcer of oral mucosa
easy bruising
progressive neurologic deterioration
HLH (2/2 EBV)
tx: stem cell transplant
life expectancy = 6yo
48
hermansky-pudlak
```
AR
HPS gene (lysosomal transport protein)
AP3B1 (formation of vesicles and protein trafficking)
results in pig dilution, plt storage defect, and ceroid lipofuscin deposition in organs
puerto rican
pigmentary dilution (OCA)
plt problems (absent dense bodies, epistaxis, ecchymosis, menorrhagia) - us not a real problem until an adult, aggravated by aspirin
pulmonary fibrosis
photophobia
poop - granulomatous colitis
pee - renal fx
palps - cardiomyopathy
life expectancy 30-50yo
```
49
Griscelli syndrome
AR
myosin Va (GS1) - neurologic issues, no immune issues - binds melanosomes to actin
Rab27a (GS2) - immune issues + HLH - encode GTPase involved in mvmt of melanosomes
variable pig dilution
silvery metallic hair
recurrent pyogenic infections
pancytopenia
immunodef
neuro def
uneven clumps of melanin in medulla of hair, no giant melanosomes
tx: stem cell transplant fi RAb27a mut otw supportive
50
Elejalde syndrome
variant of Griscelli with myosin Va mut and severe neurologic issues
no immunodef or HLH
51
PIgment Mosaicism (hypomelanosis of Ito, linear and whorled nevoid hypomelanosis, IP achromicans)
```
sporadic, due to somatic mosaicism
onset at birth/early childhood
+/- CNS (sz, mental/motor retardation)
alopecia
eye (strabismus, hypertelorism)
skeletal (scoliosis, limb length discrepancy)
tooth abnormalities (anodontia)
```
52
Incontinentia Pigmenti (Bloch-Sulzberger Dz)
XLD (lethal in males unless Klinefelters XXY)
NEMO gene mutation (NFkB essential modulator, mut allows unchecked TNF alpha mediated apoptosis)
females with missense instead of null mut have inc r/o son with hypohidrotic ectodermal dysplasia
vesicular - birth to 2 weeks (can recur after infxn, vaccine, trauma)
verrucous - 2- 6 weeks
hyperpigmented - 3-6 months
hypo pigmented - 20-30yo (diminished hair, eccrine glands, and sweat pores)
patchy scarring alopecia (vertex)
absent or peg shaped teeth (most common extracutaneous finding)
nail dystrophy
CNS (sz, delayed psychomotor dvlp)
eyes (retinal vasc abn, blindness, cataracts, optic atrophy, strabismus)
breast hypoplasia
palate hypoplasia
painful keratotic subungual tumors (10%)
eosinophilia, leukocytosis
53
Piebaldism
AD
c-kit gene (pro to-oncogene, TKR family) - defective melanocyte migration and development
also SLUG mut
white forelock
irreg shaped leukoderma favoring the anterior trunk, extremities, forehead (spares hands, feet, hips, shoulders)
present at birth, elbows and knees but not hands or feet, lack of convex borders distinguishes from vitiligo
54
Vogt-Koyanagi (+/- -Haradi)
autoimmune? reaction to virus
b/l granulomatous uveitis - often the first sign
aseptic meningitis (this seen in the Haradi variant)
followed by:
BILATERAL
vitiligo
poliosis
deafness,
dysacousia (in which certain sounds produce discomfort)
alopecia,
**bilateral as opposed to unilateral in Alezzandrini
55
Alezzandrini
autoimmune like vogt-koyanagi?
unilateral degenerative retinitis followed by
bilateral deafness and
UNILATERAL vitiligo and poliosis
56
Waardenburg Syndrome Type 1
AD
PAX3 (transcription factor)
white forelock, leukoderma, heterochromia iridis
synophorus, dystopia canthorum, broad nasal root
deafness uncommon
57
Waardenburg Syndrome Type 2 (tietz syndorme)
AD
MITF (txn factor)
forelock, leukoderma, heterochromic iridis
deafness common
58
Waardenburg Syndrome Type 3
AD
PAX3
forelock, leukoderma, heterochromic iridis
upper limb abn (hypoplasia, syndactyly, flexion contractures)
rare neural tube defects
59
Waarderburg Syndrome Type 4
AD SOX10 (txn factor)
AR EDN3 (endothelin-3), EDNRB (endothelin receptor)
forelock, leukoderma, heterochromic iridis
hirschsprungs disease (absent enteric ganglia)
deafness common
CNS disease
60
McCune-Albright syndrome (polyostotic fibrous dysplasia)
sporadic
GNAS1 gene (encodes alpha subunit of Gs adenylate cyclase, activating mutation)
large coast of maine cafe au lait
endocrine (*precocious puberty, hyperpara, hyperT, acromegaly)
fibrous dysplasia of bones (pathologic fractures, sclerosis at base of skull, shepards crook deformity of proximal femur)
61
Russell-Silver Syndrome
```
triangular facies
short stature
hemihypertrophy
clinodactyly of 5th finger
syndactyly of 2nd/3rd toes
precocious puberty
cryptorchidism/hypospadius
```
62
Sturg-Weber Syndrome (encephalofacial or encephalotrigeminal angiomatosis)
sporadic
GNAQ mutation (somatic activating mutation)
facial PWS (us V1 and unilateral but can be bilateral)
congenital or acq ipsilateral ocular abn (glaucoma)
leptomeningeal angiomatosis ipsilateral (sz, motor dysfunction, MR, intracranial "tram-track" calc)
10-15% of pts with V1 PWS have SWS
63
Bonnet-Dechaune-Blanc syndrome (aka Wyburn-Mason)
facial PWS + ipsilateral cranial and retinal AVMs
64
Klippel-Trenauney Syndrome
```
sporadic
vascular malformation of limb with gigantism of limb
lymphatic and deep venous insuff
painful, edematous, ulcers, cellulitis
intermittent claudication, lymphedema
DVT with plum emboli
urinary/GI vascular lesions
coagulopathy, CHF
```
65
CM-AVM syndrome
```
AD
RASA1 mutation
congenitaal and acquired PWS
increased incidence of AVMs inc intracranial and spinal
AVMs can rupture
```
66
parkes Weber (KT-Weber)
multiple AVMs with hypertrophy
67
Proteus Syndrome
sporadic
activating mutation in AKT1 (upstream of PTEN)
Proteus = greek god who change his shape at will = dramatic variation in manifestations
HK epidermal nevi
PP cerebriform connective tissue nevi
cap malformation
hemangiomas
lipomas
assx growth with gigantism of hands/feet
hyperostoses of epiphyses and skull (esp *auditory canal)
bilateral ovarian or parotid cystadenomas
68
Cobb Syndrome (cutaneomeningospinal angiomatosis
rare, sporadic
cutaneous vascular malformation with a vascular malformation involving the same metamere of the spinal cord
dermatomal cap malformation = MRI of spine
kyphoscoliosis common
spinal AVM = neuro defects and vertebral body abn (pain weakness, muscular atrophy)
69
Von Hippel Lindau
```
AD
VHL (tumor suppressor)
PWS of face (rarely)
bilateral retinal/cerebellar hemangioblastomas
inc renal and pancreatic ca
pheo
progressive and fatal by 40
```
70
Beckwith Weidemann Syndrome
```
AD (but most often sporadic)
KIP2 gene (inh of G1 cyclin)
circular depressions over rim of helices
linear earlobe creases
central glabellar facial vasc malform
macroglossia, visceromegaly, hemihypertrophy of tissue/viscera
abdominal wall defects
Wilms tumor (kidney)
hepatoblastoma
adrenocortical carcinoma
infantile hypoglycemia
```
71
Rubinstein-Taybi syndrome
```
sporadic
CREB binding protein
vascular malformation
multiple pilomatricomas
broad thumbs or great toes (brachyonychia, racket nails)
beaked nose
MR
congenital heart defects
cryptorchidism
```
72
Maffucci Syndrome
Sporadic
PTH/PTHrP type 1 recptor (bone related)
venous malformation (super or deep) of hands/feet
lymphatic malform
benign endochondromas (most common neoplasm, hard nodules on hands, feet, long bones, skull lesions result in neuro defects)
r/o chondrosarcomas 40% w/in endochondromas
angiosarcomas usually fatal
spindle cell hemangioendotheliomas
73
Blue Rubber Bleb Syndrome (Bean Syndrome)
sporadic (sometimes AD)
TIE2 (tyrosine kinase activating mutation)
mult tender cut and GI ven malform (birth, early childhood)
compressible blue papulonodules on trunk/arms
pinaful with lesional hyperhidrosis and nocturnal pain
GI bledd, intussusception
74
Cornelia De Lange Syndrome
```
sporadic sometimes AD
NIPBL (nipped beta like gene)
cutis marmorata
synophorys
trichomegaly
craniofacial abn
clinodactyly
MR, deafness, low-pitched cry
```
75
Hereditary Hemorrhagic Telangiectasia (osler-weber-rendu)
```
AD
HHT1 (endoglin, assoc with lung)
HHT2 (ALK1 assoc with liver "alk phos")
epistaxis (childhood)
mucocutaneous and GI telangiectasia (adloescence, lips, ears, oral, palms fingers, soles, nasal mucosa)
GIbleeding
pulm AVMs (also CNS, hepatic, spinal)
```
76
Hereditary Lymphedema (Milroy Disease)
```
AD
FLT4 mut - encodes VEGF receptor 3 (tyr kinase R in lymph vessels)
congenital lymphedema
chylous ascites
cystic higroma
```
77
Lymphedema-distichiasis syndrome
```
AD
FOXC2 mut, encodes txn factor
late-onset lymphedema
double row of eyelashes (distichiasis)
trichiasis (eyelashes grow towards eyeball)
```
78
Noonan syndrome (aka cardiofaciocutaneous syndrome)
```
AD
PTPN11 (encodes protein tyrosine phosphatase Shp2)
SOS1
KP atrophicans (ulerythema)
cystic hygroma (macrocystic lymphatic malformation), most common on post neck
Webbed neck
*hypertelorism
*undescended testes
low posterior neck hairline
keloid formation
lymphedema
*pulm stenosis
* shared features with LEOPARD
```
79
Turner Syndrome (gonadal dysgenesis)
XO genotype
short stature
webbed neck
cystic hygroma
low posterior hairline
congenital lymphedema (us transient and gone by 2)
nails - short and hyperconvexity
abn sexual development (ovarian dysgenesis)
primary amenorrhea
aortic coarct
skeletal abnormalities (micrognathia, broad ‘shield’ chest, kyphoscoliosis, Madelung deformity (wrist), cubitus valgus - angled forearms away from body)
hearing defects
renal abnormalities
endocrinopathies (most notably involving the thyroid and glucose metabolism)
80
Meige Lymphedema (Hereditary Lymphedema II)
late onset around puberty
81
Osteogenesis Imperfecta
```
AD/AR
type 1 collagen gene mut (alpha1 and alpha2 chains)
decreased elasticity
easy bruising
otosclerosis (hearing loss, adolescence)
MVP
Blue Sclera
```
type I: mildest and most common (50% of cases) fracture, bowing, kyphoscoliosis
type II: die in utero or shortly after birth, beaded ribs, crumpled humeri, abducted thighs
type III: Severe deformities. non-ambulatory. Triangular face, dentinogenesis imperfecta (translucent blue teeth)
type IV: Milder than OI III, dentinogenesis imperfecta, sclera nl or gray
82
Blue Sclera differential
```
Alkaptonuria
Down's syndrome
EDS
Marfans
OI
Nevus of Ota
Fanconi's
PXE
"All DEMONs Fly Past"
```
83
EDS Classic (type I Gravis and type II Mitis)
type I - AD Col5A1 (alpha 1chain) or Col5A2 (alpha 2 chain)
Type II - AR Tenascin X deficiency
hyper extensible skin (but returns to nl as opposed to cutis lax a)
joint laxity
*skin fragility (fish mouth scars and cigarette paper)
Gorlins sign
absence of frenulum (inferior labial or lingual)
*molluscoid pseudotumors (spongy, scars, pressure points)
MVP
premature rupture of membranes (gravis Type I)I, occurs if baby or mom has dz)
piezogenic pedal papules
84
EDS Hypermobility (type III, benign hypermobile)
AD
TNXB (tenascin X in 10%) or type V procollagen
*joint hyper extensibility (subluxations, dislocations)
DJD
*minimal skin involvement
85
EDS Vascular (type IV, arterial-ecchymotic)
AD
COL3A1 (type III col)
*most devastating form
thin translucent skin but not hyper extensible
visible veins
*vascular fragility (arterial, GI, uterine rupture)
*extensive bruising
hyper mobility of small joints (hand, feet)
acrogeria (aging of backs of hands)
sunken eyes, a thin upper lip, and decreased facial fat
blue sclera
pneumothorax
86
EDS Kyphoscoliosis (VI)
```
AR
PLOD (lysyl hydroxylase)
rare
*kyphoscoliosis congenital
resp problems
muscle weakness
joint laxity
*ocular fragility (glaucoma, retinal detachment)
osteopenia
```
87
EDS Arthrochalasia (VIIA and B)
```
AD
COL1A1 ( may have overlap with OI) or COL1A2 (type 1 col)
rare
marked joint hyper mobility with mod cutaneous elasticity
*dislocation of large joints
*bilateral congenital hip dislocation
scoliosis
easy bruising
*severe muscular hypotonia at birth
```
88
EDS Dermatosparaxis (VIIC)
```
AR
ADAMTS2 (procollagen N-proteinase)
rare
*extremely fragile and sagging skin
easy bruising
hernias
*high mortality mutation
(short limbs, micrognathia, blue sclera, gingival hyperplasia, abn dentition)
```
89
EDS type IX
```
reclassified as occipital horn syndrome
allelic with Menkes (ATP7A, lysyl oxidase defect)
exostosis from occipital horn
elbow deformity
radial head dislocation
```
90
EDS type XI
reclassified as familial joint hyper mobility syndrome (new type X)
91
EDS V
XLR
hyper extensible skin
orthopedic abn
bruising
92
EDS VIII (periodontal type)
AD
*periodontitis
EDS I/II findings
93
EDS X
fibronectin def
bruising
joint hypermobility
94
EDS cardiac valvular
AR
Collagen I (alpha 2 chain)
heart valve defects
EDS I findings
95
EDS progeroid
```
AR
B4GALT7 (galactosyl transferase I)
porgeroid facies
osteopenia
MR
growth retardation
skin hyper extensibility
joint hyper mobility
```
96
marfan syndrome
```
AD
fibrillin 1 and 2 defect
tall stature
joint hypermobility
pectus excavatum
ectopia lentis (upward dislocations of the lens, homocyteinuira downward dislocation)
myopia
arachnodactyly
long limbs
aortic dilation with rupture
MVP
striae
EPS
death from cardiac complications
thumb sign (thumb extends well beyond the ulnar border of the hand when overlapped by fingers)
wrist sign (thumb overlaps the fifth finger as they grasp the opposite wrist)
scuba diving - pneumothorax
limit physical activity
```
97
marfanoid habitus ddx
```
Marfans
Homocysteinuria
MEN IIB
Klinefelters
Congenital Contractural Arachnodactyly
Kallman
Loey-Dietz
```
98
Loeys Dietz
```
AD
TGFBR1 or TGFB2R
hyperextensible joints
soft velvety skin
arterial tortuosity and widespread vascular aneurysm and dissection
```
99
Homocysteinuria
```
AR
cystathionine B synthase
ectopia lentis (downward)
marfanoid habitus
*mental retardation
DVTs
Malar flush
Leg ulcers
Livedoreticularis
Myopia
Glaucoma
```
100
Pseudoxanthoma elasticum (PXE)
AR or AD
ABCC6 gene mutation (transmembrane transporter gene)
fragmented/calcified elastin of skin/eyes/ arteries
plucked chicken skin in flexures (neck, below the clavicles, axillae, antecubital fossae, periumbilical, perineum and thighs)
angioid streaks (rupture of Bruch's membrane) with retinal hemorrhage
gastric artery hemorrhage
MVP, HTN, MI, claudication (related to vascular calcification)
101
Cutis Laxa (generalized elastolysis)
AR - FBLN5 gene = fibulin 5 (also fibulin 4 can occur), more severe cardiac involvement
AD - elastin gene and FBLN5
(XLR = occipital horn syndrome = Cu transport dz - ATP7A gene = lysyl hydroxylase)
loose pendulous skin (bloodhound appearance)
arterial rupture
pulmonary art stenosis, aortic dilation
visceral diverticuli/hernia
joint dislocation
uterine/rectal prolapse
pulmonary emphysema (AR cases) - leading cause of death newborn with hypo plastic lungs
Verhoeff–van Gieson stain = decreased or absent dermal elastic fibers
Acquired cases: Marshall syndrome
type I: generalized (PCN, penicillamine, INH, deposition dz, infection)
type II: localized with fever, malaise, eos (post sweets syndrome)
102
costello syndrome
```
AD
*loose soft skin of neck, hands, feet
*ulnar deviation at wrist
*papillomata - nares, mouth, anal areas
prenatal overgrowth and polyhydramnios
postnatal FTT
coarse facies - thick lips, macroglossia, macrocephaly
severe short stature
MR
hypertrophic CM
```
103
Congenital Contractural Arachnodactyly
```
AD
fibrillin 2
*crumpled ears
long limbs
arachnodactyly
```
104
Focal Dermal Hypoplasia (goltz syndrome)
```
XLD
PORCN gene = O-acyltransferase - controls secretion of Wnt
lethal in males
linear atrophy following Blaschkos lines with fat herniation and telangiectasia
osteopathia striata
colobomas
oral papillomas (raspberry like)
lobster claw deformity of hand
syndactyly
alopecia
thin nails
hypodontia with enamel defects
notched ala
"FOCAL" female, osteopathia, colobomas, alopecia, lobster
```
105
Van Allen Myhre syndrome
severe form of Goltz with lobster hand and foot deformity
106
Berardinelli-Seip Congenital Lipodystrophy (Congenital generalized lipodystrophy )
```
BSCL2 gene mutation (nuclear lamins)
generalized lipodystrophy
Acanthosis nigricans
HL
DM
hepatomegaly
```
107
Familial Partial Lipodystrophy (Köbberling–Dunnigan syndrome)
```
AD
LMNA gene mutation (lamin A/C) (same as progeria)
symmetric lipoatrophy of trunk/limbs
tuberoeruptive xanthomas
acanthosis nigricans
HTG
```
108
Buschke-Ollendorf Syndrome
AD
LEMD3 (MAN1) gene, encodes inner nuclear membrane protein which leads to inc TGF-B signalling
increase in desmosine (elastin specific AA)
elastomas (dermatofibroma lenticularis disseminata) - trunk, buttocks, arms
osteopoikilosis (ectopic calicifications in bone)
not fracture prone
short stature, otosclerosis, spinal stenosis,209 and supernumerary vertebrae and ribs
109
Cutis Verticis Gyrata
1ry - develops at puberty, can be a/w MR, sz, cataracts, optic atrophy, pachydermoperiostosis
2ry - hyperpituitarism, acromegaly, myxedema, insulin resistance, turner, noonan, fragile X, klinefelters, TS, Graves, HyperIgE, paraneoplastic, hereditary neuralgic amyotrophy
110
Lipoid Proteinosis (Urbache-Wiethe Disease, hyalinosis cutis et mucosae)
AR
ECM1 gene mutation
abnormal deposition of hyaline material at the dermal-epidermal
*string of pearls over eyelids
hoarse voice (infancy)
*bean-shaped temporal-hippocampal calcification (above sella turcica) rarely with sz
large wooden tongue
waxy yellow papules on face/oropharnx - can look cobblestoned
eversion of lips studded with tiny yellow nodules
hypertrophic lesions at the corners of the mouth
linear or varioliform scarring of the face
most common for kids to have flaccid vesicles, bullae crusted papules
parotid pain and recurrent parotid swelling as a result of obstruction of Stensen’s duct
adults - hyperkeratotic plaques on elbows, knees, and palms
nl lifespan
111
Beare-stevenson Cutis Gyrata Syndrome
```
FGFR2 gene
cutis gyrata
AN
anogenital anomalies
craniosynostosis
furrowed palms/soles
natal teeth
```
112
Menkes Disease (trichopoliodystrophy)
```
XLR (males)
ATP7A mut, encodes ATP dep Cu transporter
dec serum copper/ceruloplasmin levels
*pili torti (most common, carrrier females can have this) trichorrhexis nodosa, short brittle steel wool hair, monilethrix
sparse eyelashes/eyebrows
cupids bow upper lip
*progressive CNS deterioration (major morbidity)
sz
temperature instability
*tortuous arteries
doughy redundant skin
metaphyseal widening in the long bones
increased susceptibility to infection,
death by age 3 or 4 years
```
113
Monilethrix
AD
human hair keratin hHb1 (K81) and hHb6 (K86)
beaded hair with elliptical nodes along hair shaft
hair is fragile and coarse, looks like stubble often
koilonychia
KP
114
trichorhinophalangeal syndrome
```
AR/AD
TRPS1 gene
sparse hair (loose anagen)
pear-shaped nose
elongated philtrum, thin upper lip, supernumerary incisors, and receding chin
brachydactyly, deviation of the middle phalanges
cone-shaped epiphyses (type II)
congenital hip dysplasia
short stature
```
115
uncombable hair syndrome
```
AD, AR or sporadic
pili trianguli et canaliculi (triangular cross-section, longitudinal groove) - not specific
blonde spun glass hair
possible improvement with biotin
can also have loose anagen
```
116
Tricho-dento-osseous syndrome
```
AD
DLX3 homeobox gene
curly/kinky hair at birth (may straighten after puberty)
dental pits
inc bone density
```
117
Bjornstadt syndrome
AR
pili torti
deafness
nl intelligence and lifespan
118
Loose Anagen Syndrome
```
sporadic or AD
preschool girls with blond hair
grows slowly
soft hair
easily falls out
inner root sheath defect
kids usually grow out of this
```
119
Woolly hair nevus
```
AD or AR
negroid hair in non-negroid person
sparser and lighter in color
can have underlying epidermal nevus
diffuse woolly hair can be assoc with carvajal or naxos
```
120
Nevoid Localized Hypertrichosis
| anterior cervical hypertrichosis
localized patch of hair
121
Witkop syndrome (Trichodental syndrome )
```
AD
MSX1 mut
tooth and nail syndrome
an ectodermal dysplasia syndrome
fine dry slow growing hair
spoon shaped nails
conical teeth or anodontia
```
122
Papular Atrichia
AR
human homolog of mouse hairless gene mut
loss of natal hair with subsequent generalized atrichia
123
Marie-Unna hypotrichosis
AD
U2HR
congenital absence of scalp and facial hair
new hair grows - coarse, flattened, twisted
at puberty hair becomes sparse and eventually only a fringe of hair remains
widely spaced upper incisor teeth
124
Nail-Patella Syndrome
```
AD
LMX1B
triangular lunulae
absent/hypoplastic patella
lester iris = clover leaf shaped zone of darker pigment around central part of iris
posterior iliac horns
thicken scapula
glomerulonephritis (check UA, consider US)
radial head subluxation
```
125
pachyonychia congenita
```
AD
K6a or K16 (type I)
K6b or K17 (type II)
Type I = Jadassohn-Lewandowsky
dystrophic nails, PPK, oral leukokeratosis (benign)
type II = Jackson Lawler
dystrophic nails, PPK (painful), steatocystomas, epidermal cysts, natal teeth
hoarseness K6a only
(typing is now just historical)
```
126
natal teeth (already present at birth)
Pretty Happy Baby
PC
Hallerman-Steife
Baer-sTevens
127
ichthyosis vulgaris
AD
FLG gene
decreased/absent profilaggrin (KHGs)
fine white scales on extensor surfaces (infancy, early child)
flexures spared
hyperlinear palms
atopic
KP
infants/kids with facial involvement - resolves in adolescence
histo: attenuated/absent granular layer, retention HK
acquired form: nutritional d/o, hypoT, sarcoidosis, dermatomyositis, leprosy, TB, HIV, lymphomas
128
pityriasis rotunda
rare variant of acquired ichthyosis
brown round scaly patches on trunk/ext
japanese, african, west indian
tx resistant unless underlying condition txd
129
Collodion membrane
```
CIE
LI
Harlequin
sel healing collodion
bathing suit ichthyosis
conradi
trichothiodystrophy
neutral lipid storage disease (lipid vacuoles in leukocytes and lipid vacuoles in basal epidermis)
```
130
X linked ichthyosis
XLR - males
ARSC 1 encodes steroid sulfatase (STS, arylsulfatase C)
steroid sulfates is secreted and cleaves cholesterol sulfate into cholesterol
cholesterol sulfate is an epidermal protease inhibitor and prevents breakdown of desmosomes leading to corneocyte retention
infancy - mild erythroderma and large translucent scales
childhood - adherent brown scales over extremities, trunk, neck
spares palms/soles/face, flexures
seasonal variation
mother of affected pt- low/absent estrogen in urine/amniotic fluid - labors fails to progress
comma shaped corneal opacities
cryptorchidism
r/o testicular cancer, ALL
histo: HK or PK over nl or thickened granular layer
test: serum lipoprotein electrophoresis (accum chol sulfate), FISH gene deletion, dec arylsulfatase C act in leukocytes
think C - arylsulfatase C, corneal opacities, cryptorchidism, cessation of labor, cholesterol sulfate
131
Kallman syndrome
```
XLI
MR
hypogonadism
anosmia
continguous gene nut with XLI
```
132
Lamellar Ichthyosis (nonbullous CIE)
AR
mutation in TGM1 or missense ABCA12 mut (ATP binding cassette A12)
collodion membrane
erythroderma (infancy)
childhood - thick dark scales with prominent flexural and facial involvement
ectropion, eclabium, scarring alopecia, nail dystrophy
PPK, heat intolerance, hypernatremia
histo: massive OK HK, acanthosis, inc granular layer
133
CIE (nonbullous CIE)
AR
TGM1 gene, few ALOXE3 (lipoxygenase 3) or ALOX12B (12R-lipoxygenase) gene
colloidion
generalized erythroderma with powdery scale
flexures involved
PPK
ectropion, scarring alopecia
nail dystrophy (mild)
heat intolerance
IUGR, FTT
inc lamellar granules but structurally abn
134
superficial epidermolytic ichthyosis (ichthyosis bullosa of siemens)
AD
keratin 2e gene defect
mild erythroderma and blistering at birth
childhood - brown HK plaques over joints, flexures, dorsal hands, and feet
spares palms/soles
mauserang sign - full thickness shed of scale - denuded area
histopath: superficial epidermolysis
135
bathing suit ichthyosis
AR
TGM1 mut
collodion
bathing suit distribution 2/2 temp sens
136
self healing collodion
AR
TGM1
variant of LI
collodion but heals in dry environment 2/2 hydrostatic sens TGM1 mut
137
ARCIs
```
AR
CIE
LI
Harlequin
bathing suit
self healing collodion
```
138
keratinopathic ichthyoses
AD
superificial epidermolytic ichthyosis (Siemens)
epidermolytic ichthyosis (BCIE)
139
epidermolytic icthyosis (EHK, bullous CIE)
AD
K1 or K10
birth - erythroderma, bullae
3months - verrucous plaques
flexures involved (corrugated cardboard) - body odor from scale and bacterial overgrowth
PPK (worse with K1)
FTT, hypernatriemia dehydration, recurrent infxn (bronchopneumonia, sepsis)
annular variant
histo: massive OK HK, hypergranulosis, cytolysis of granular layer/suprabasal layers, clumped tonofilaments (keratin intermediate filaments)
140
Harlequin Ichthyosis
```
AR
ABCA12 - nonsense mut
hard thickened restrictive collodion
severe ectropion, eclabium, mitten like hands and feet
death often due to resp or sepsis
oral retinoid may prolonged survival
histo: absent lamellar granules
neonatal arthrogryposis (joint contractures) - suspect dx
```
141
netherton syndrome
AR
SPINK5 (LEKTI - lymphoepithelial kazal-type-related inhibitor - serine protease inh - def causes inc degradation of desmosomes and dec barrier)
birth - generalized erythroderma, scaling, collodion?, FTT (intestinal villus atrophy)
triad: congenital ichthyosis (ichthyosis linearis circumflexa or CIE) + trichorrhexis invaginata (short dry, lusterless hair, check eyebrow) + atopy
trichorrhexis nodosa most common hair finding
immunodeficiency
adults inc r/o HPV
inc absorption of topicals b/c impaired barrier
142
Sjogren-Larsson Syndrome
AR
FALDH gene (fatty aldehyde dehydrogenase, AKA ALDH3A2) - synthesis of epidermal lipids and catabolism of sphingolipids in the brain
infant - generalized ichthyosis
pruritus (accum of leukotriene B4)
child - dark/yellow scales on lower abdomen, flexures, and neck with PPK
spastic ditretraplegia (scissor gait)
MR
perifoveal "glistening white dots" in ocular fundus, photophobia
"FALl DHown = gene + spastic gait"
"stupid, spastic, scaly, swede, seeing stars"
143
CHILD syndrome
XLD (lethal in males)
NSDHL gene encodes NADPH steroid dehydrogenase-like protein (enzyme 3b-hydroxysteroid dehydrogenase)
inability to syn cholesterol and build up of intermediates
congenital hemidysplasia, ichthyosiform erythroderma, limb defects
birth - unilateral ichthyosiform erythroderm
child - eythema fades, hyperkeratosis persists (body folds, can be blashkoid)
ipsilateral: alopecia, organ aplasia/agenesis (heart, renal), skeletal defects (cleft palate, hypoplasia of digits, ribs)
stippled epiphyses
severe nail dystrophy
tx: topical statin + cholesterol
histo: verruciform xanthoma
144
CHIME syndrome (Zunich neuroectodermal syndrome)
```
PIGL gene
Coloboma (retinal)
Heart defects
Ichthyosiform dermatitis
MR
Ear - conductive hearing loss, cupped ears with rolled helices
```
brachydactyly
hypertelorism
epicanthal folds,
short philtrum
145
Conradi-Hunermann Syndrome (XLD chondrodysplasia punctata)
XLD
EBP gene (emopamil binding protein - AKA 3beta-hydroxysteroid 8,7 isomerase - sterol isomerase activity)
accumulation of 8,9 cholesterol and 8-dehdyrocholesterol and impaired cholesterol synthesis
birth - ichthyosiform erythroderma --> hyperkeratosis
child - linear/patchy follicular atrophoderma and ice pick-like scars, psoriasiform lesions with ptychotropism
chondrodysplasia punctata (stippled epiphyses - infancy)
cataracts
deafness
scarring alopecia
frontal bossing
flat nasal bridge
short stature
146
Rhizomelic Chondrodysplasia punctata
```
AR
type I PEX7 (peroxisomal biogenesis disorder)
Type II DHAPAT
type III alkyl DHAP synthetase
Diffuse fine scaling and erythema
Alopecia
Punctate chondrodysplasia
Cleft vertebrae
Resp compromise
Death in infancy
```
147
KID syndrome (keratitis - ichthyosis- deafness)
```
AD GJB2 (connexin 26)
Presents at birth with symmetric Hk plaques over knees, elbows, face
Grainy or stippled PPK
Congenital sensorineural deafness
Vascularizing keratitis with blindness, photophobia
Abn teeth/nails
Infxn
R/o SCC
```
148
Refsum disease (phytanic acid storage disease)
AR
PAHX (PHYH) gene - peroxisomal phytanyl CoA hydroxylase
PEX7 (biogenesis factor 7)
Excessive accumulation of phytanic acid - derived from dietary chlorophyll
Presents in childhood/adolescence
Ichthyosis vulgaris
Cerebellar ataxia
Peripheral neuropathy
Salt and pepper retinitis pigmentosa (night blindness)
Deafness
"Deaf and scaly old Mr Refsum likes to eat weed with salt and pepper and do a funny dance"
Treat with dietary restriction of phytanic acid
149
Infantile Refsum
PEX1, PEX2, or PEX26
| Onset at birth
150
Darier's disease (keratosis follicularis)
AD
ATP2A2 - encodes SERCA2 (sracoendoplasmic reticulum ca ATPase)
HK papules coalescing into warty apps in seb Derm dist.
Acrokeratosis verruciformis of Hopf-verrucous apps and dorsal hands and feet
Palmar keratosis/ pits
Candy cane nails
V shaped nicks
Subungual HK
cobblestoning of oral and anogenital mucosa
Histo: acantholysis with corp ronds and grains
Can be worsened with lithium
151
Non-epidermolytic PPK ( unna thost syndrome)
```
AD
Keratin 1
Diffuse with erythematous border
Hyperhidrosis
Secondary tinea infections
Pitted keratolysis
No transgradie
```
152
Epidermolytic PPK (Vorner Syndrome)
AD
K1 or K9
Epidermolytic
Histo shows epidermolytic HK
153
Mal de maleda
```
AR
ARS component B mutation which encodes
SLURP-1 - encodes secreted ly-6/uPar related protein - involved in epidermal homeoregulation and TNF alpha inhibition
Transgradient hands/feet/elbows/knees (does not respect Wallace lines)
Hyperhidrosis with Mal odor
Secondary infxn
*Perioral erythema
Thickened nails
```
154
Vohwinkel Syndrome (classic, Keratoderma Hereditaria Mutilans)
```
AD
GJB2 (connexin 26)
mutilating keratoderma + deafness
diffuse honeycomb-like PPK
psuedoainhum
starfish shaped keratoses of joints
sensorineural deafness
linear keratotic plaques of knees
scarring alopecia
```
155
Vohwinkel variant
AD
Loricrin (cornified envelope protein)
mutilating keratoderma + generalized ichthyosis
no deafness
156
Papillon-Lefevre
AR
CTSC gene - cathepsin C (lysosomal protease)
PPK + periodontitis
early loss of teeth
transgradient erythematous PPK with psoriasiform lesions on extremities
calcification of falx/tentorium
hyperhidrosis
157
Haim-Munk Syndrome
AR
CTSC gene - cathepsin C (lysosomal protease)
papillon-lefevre (PPK + periodontitis) + onychogryphosis (rams horn nails)
arachnodactyly
acrosteolysis (resorption of distal bony phalanges)
158
Naxos Disease
```
AR
JUP gene - Plakoglobin
PPK+ wooly hair + cardiomyopathy (r sided)
arrythmias
We Are NPR
```
159
Carvajal Syndrome
AR
desmoplakin
PPK (first year of life, striate not diffuse) +wooly hair + L sided cardiomyopathy (dilated)
"LCD"
160
Olmstead sydnrome
```
? K 5 and K 14
newly identified mut - constituitively active TRPV3 (transient recpetor protein vanilloid 3 cation channel)
mutilating PPK + periorificial plaques
PPK initially focal then widespread
flexion deformities
autoamputation
erythematous HK perioral plaques
alopecia
corneal defects
nail dystrophy
rr/o SCC inc
ddx: acrodermatitis enteropathica
```
161
nonepidermolytic PPK with deafness
connexin 26 or A7445G (mitochondrial)
| PPK + sensorineural deafness
162
Bart-Pumphrey
AD
GJB2 - connexin 26
PPK with knuckle pads, leukonychia, deafness
163
Keratoderma climactericum
scaly keratotic soles of feet in post menopausal women
164
Howel-Evans Syndrome
```
AD
TOC gene (tylosis-oesophageal carcinoma)
focal PPK over pressure areas (balls of feet > hands)
oral leukokeratosis
r/o esophageal cancer
```
165
Richner-Hanhart Syndrome (tyrosinemia type II)
AR
hepatic tyrosine amino-transferase (TAT)
pseudoherpetic keratitis
dendritic corneal ulcers (tyrosine crystal deposition)
painful focal PPK (pain = Handhurt)
progressive MR
treated with diet restricted in tyrosine and phenylalanine
166
punctate PPK (keratosis punctata palmaris et plantaris)
AD
begins during adolescence
punctate keratoses on palms
palmar creases of African origin pts
167
Acrokeratoelastoidosis
AD
skin-colored papules inv hands and feet
adolescence
168
striate PPK
```
AD
desmoglein 1 and desmoplakin 1
onset in childhood
HK linear plaques on volar fingers
diffuse /focal plaques on proximal palms/soles
```
169
erythrokeratoderma variabalis (Mendes de Costa)
AD
GJB3 and GJB4 (connexin 30.3 and 31)
erythematous migratory patches (may last min to days)
fixed HK plaques (elbows, knees, achilles, soles)
50% with PPK
face, scalp, flexures spared
hypertrichosis
170
Progressive Symmetric Erythrokeratoderma
AD
loricrin or connexin 31
fixed hyperkeratotic erythematous plaques over joints/extremities
50% with PPK
171
hidrotic ectodermal dysplasia (Clouston syn)
```
AD
GJB6 (connexin 30)
hypotrichosis
diffuse PPK
*nail dystrophy
*normal teeth and sweating
MR
ocular abnormalities
```
172
hypohidrotic (anhidrotic) ectodermal dysplasia (Christ-Siemens-Touraine)
```
XR - EDA (ectodysplasin A)
AD, AR - EDAR gene (ED-A receptor) - NFkB pathway
hypotrichosis
*periorbital hyperpigmentation
*absent or conical teeth
*sweating with head intolerance
*normal nails
saddle nose
everted thick lips
inc bronchopulmonary infections
```
173
Ankyloblepharon-ectodermal-dysplasia-clefting syndrome (AEC, Hay Wells)
```
AD
p63
chronic erosive scalp dermatitis
abnormal granulation tissue
recurrent bacterial infections
ankyloblepharon (fusion of top and bottom lid)
hypotrichosis
80% cleft lip/palate
```
174
ectodermal dysplasia-ectrodactyly-clefting syndrome (EEC, split hand-split foot-ectodermal dysplasia-clefting)
```
AD
p63
ectrodactyly (split hand/foot)
hearing loss
nail dystrophy
+/- PPK
70% cleft lip/palate
sparse and dry hair
hypodontia
```
175
rapp-hodgkin syndrome
```
AD
p63
mid facial hypoplasia
cleft lip/palate
scalp dermatitis
dec sweating
nail dystrophy
hypodontia
```
176
Ectodermal dysplasia/skin fragility syndrome
```
AR
plakophilin-1
trauma-induced bullae (infancy)
sparse hair
thick dystrophic nails
```
177
whitkop tooth and nail syndrome (trichodental syndrome)
```
AD
MSX1
rare
hypodontia (conical and narrow crowns)
spoon nails
```
178
ADULT syndrome
acral, dermato, ungual, lacrimal tooth syndrome
ectodermal dysplasia with nl sweating
EDA mutation
179
Schopf-Schulz Passarge
AR
WNT10A - cutaneous signaling molecule involved in ectodermal appendageal development
hydrocystomas of eyelids
hypotrichosis
hypodontia
nail dystrophy
multiple palmoplantar eccrine syringofibroadenomas
180
Naegeli–Franceschetti–Jadassohn syndrome
```
diffuse NEPPK
KRT14
abnormal sweating
reticulate hyperpigmentation
absence of dermatoglyphics
other ectodermal anomalies
```
181
dermatopathia pigmentosa reticularis
```
diffuse NEPPK
KRT14
abnormal sweating
reticulate hyperpigmentation
absence of dermatoglyphics
other ectodermal anomalies
```
182
Huriez Syndrome
```
AD
PPK + scleroatrophy - pseudosclerodermatous appearance
reticulate erythema dorsal hands
no raynauds
r/o SCC of palms/soles
```
183
Micali syndrome
PPK + scleroatrophy
| R spondin 1
184
alkaptonuria
```
AR
homgentistic acid oxidase
blue-gray pigmentation of cartilage (ear helix), sclera and skin (axilla)
urine darkens on standing
arthritis
```
185
biotinidase def
```
AR
alopecia
periorificial dermatitis
developmental delay
seizures
treat with biotin
```
186
fabry disease
XLR
alpha-galactosidase A
- ceremide trihexisidase accumulates
- glycosphingolipids in vascular endothelium
multiple angiokeratomas
extremity pain - often present with pain crises
parasthesias
whorl-like corneal and lenticular opacities
birefringent lipid globules in urine (maltese cross)
MI/CVA
renal disease - significant morbidity
GI
187
fucosidosis
```
AR
alpha-fucosidase
mult angiokeratomas
coarse facies
growth retardation
dysostosis multiplex - severe abnormalities in development of skeletal cartilage and bone
MR
```
188
gaucher disease
AR
alpha-glucosidase (glucocerebrosidase)
type I adult - diffuse brown pigmentation, low plt, HSM, bone pain, ehrlenmeyer flask deformity of femoral midshaft
type 2 infant - no skin fx, severe, rapid death
type 3 child - chronic neuropathy
189
Hartnup disease
```
AR
SLC6a19 - encodes BOAT1 - dec renal aa transport
also fail to absorb tryptophan --> nicotinic acid def --> pellagra like eruption
photosensitivity
ataxia
tremors
ocular
MR
psychosis
tx with niacin
```
190
Holocarboxylase synthestase def
```
AR
alopecia
perioral/perianal dermatitis
metabolic encephalopathy
metabolic acidosis
treat with biotin
```
191
hunter disease
XLR
iduronidate sulfatase (IRS will HUNT you down)
firm flesh colored to white papules coalescing over scapula or over buttocks, nape of neck, upper arms, thighs
192
hurler disease
```
AR
alpha-L iduronidase ( L = hurLer)
MR
HSM
hernia
opacities
gargoyle like features
extensive dermal melanocytosis
```
193
lesch-nyhan syndrome (juvenile gout)
```
XLR
HGPRT def
build up of uric acid in body fluid
self mutilation
orange crystals in diaper
gout
choreoathetosis
MR
misuse vit B12 - megalloblastic anemia
```
194
lipoid proteinosis
AR
ECM1 defect
1st stage: vesicles face, ext, mouth - heal with ice pick scars
2nd stage: pearly papules on eyelids
verrucous papules on extensor surfaces
hippocampal calc (attacks of rage and psychomotor or grand map seizures)
infiltrating deposits on lips and tongue (wooden)
hoarseness ( vocal cord infiltration)
Slow to heal, broad scars
195
Bazex syndrome
```
XLD
Follicular atrophoderma
Hypotrichosis - pili torti
facial milia
trichoepitheliomas
vellus hair cysts
BCC
unique features:
follicular atrophoderma (can be seen on dorsal hands, extremities)
hypohidrosis
comedones
facial and neck pigmentation
```
196
Rombo syndrome
```
XLD
Hypotrichosis - pili torti
milia
trichoepitheliomas
vellus hair cysts
BCC
photosensitivity
atrophoderma vermiculata (limited to cheeks, looks like acne scars, honeycomb appearance)
```
197
Chronic granulomatous disease
XLR
NADPH oxidase gp91
leukocytes w/o oxidative burst - cannot kill intracellular bacteria and fungi
nicotinamide dinucleotide phosphate (NADPH) oxidase complex is reduced
recurrent pna
HSM
LAD
skin - facial and perianal abcesses and pyodermas
staph, gram neg, fungal
seb derm, sweets, aphthous somatitis, lupus like rash, scalp folliculitis
198
Kleinfelters
XXY
tall stature with long limbs
Reduced body hair
LE varicosities with recurrent leg ulcers
199
Wilson's disease
Retention of copper
Greenish discoloration of face, neck, genitalia
Blue lunulae of the nails
Kayser fleischer rings
200
Hemochromatosis
```
AR
Increased intestinal iron absorption
Metallic gray hyper pigmentation
Koilonychia
Sparse hair
Hypoganadism
Arthritis
Hepatomegaly
Cardiac fx and arrx
```
201
Ichthyosis with confetti
KRT10
Sporadic
frameshifts mut - arginine-rich C-terminal peptide that redirects keratin 10 from the cytokeratin filament network to the nucleolus
202
Neiman Pick disease
```
AR
spingomyelinase def (SMPD1)
type A: FTT, HSM, neuro deterioration
type B: min neuro dz, xanthomas, histocytic inf in viscera, psychomotor delay, muscle weakness, blindness (cherry red spots)
```
203
phenylketonuria
```
AR
SLC39A4 (zinc transporter)
diffuse hypopig
eczema
MR
sclerodermoid changes
blonde hair, blue eyes
urine and skin with mousy odor
```
204
prolidase deficiency
```
AR
prolidase
skin fragility
ulceration and scarring LEs
photosens
MR
recurrent infxn
```
205
wilson's disease
```
AR
ATP7B (ATPase copper transporting enzyme)
copper accumulation in liver/brain/cornea
cirrhosis
blue lunula
kayser Fleischer rings
ataxia
dementia
hepatomegaly
```
206
RAS-ERK-MAPK pathway
include: Cardio-facio-cutaneous syndrome, Costello, LEOPARD, NF, and Noonan
207
Brooke speigler
CYLD gene
Cylindromas
Trichoepitheliomas
