Genoderms Flashcards
XP - inheritance, gene, clinical findings
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
XP variant
AR
DNA polymerase ( post replication repair)
same as XP but no neuro sx (no deafness)
DeSanctis-Cacchione syndrome
AR
usually XPA (form of XP)
term for severe neurologic abnormalities in XP- MR, deafness, ataxia
XP genes
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
Cockayne Syndrome
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
cockayne -XP overlap gene
XP-B,D,G (G most common)
“BiG Deal”
no increased r/o skin cancer but develop pigment abnormalities
Aicardi-Goutieres syndrome
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
trichothiodystrophy (PIBIDS, Tay Syndrome)
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
bloom syndrome (congenital telangiectatic erythema)
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”
rothmund-thompson (poikiloderma congenitale)
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
dyskeratosis congenita (zinsser-Engman-Cole syndrome)
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
ataxia telangiectasia (Louis Bar Syndrome)
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
Fanconi syndrome
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
basal cell nevus syndrome (gorlin syndrome)
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
NF-1 (Von Recklinghausen dz)
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
Legius Syndrome
SPRED1
CALMs and axillary/inguinal freckling
“spread your legs”
NF-2 (bilateral acoustic neurofibromas)
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)
Carney Syndrome (NAME or LAMB)
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
muir torre syndrome
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)
tuberous sclerosis ( bourneville syn)
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
cowden syndrome (multiple hamartoma syndrome)
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
Lhermitte-Duclos
PTEN mutation
rare slow growing tumor in the cerebellum
Assoc with cowdens and can have same manifestations and r/o cancer as Cowdens
Bannayan Riley Ruvalcaba (bannayan-Zonana)
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
CLOVES
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
MEN1 (wermer syndrome)
AD MEN1 mutation = menin protein (tumor suppressor) *CALMs angiofibromas, collagenomas, lipomas pituitary parathyroid pancreas
MEN2A (sipple syndrome)
AD RET mutation (tyrosine kinase receptor) parathyroid medullary thyroid (2=T) pheochromocytoma *lichen or macular amyloidosis hemangiomas, genital lentigines, hamartomas, lipomas
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)
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
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)
Laugier–Hunziker syndrome
macular hyperpigmentation of the lips and buccal mucosa
melanonychia striata
no visceral manifestations, no cancer risk
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
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"
dysplastic nevus syndrome
AD CDKN2A (p16 tumor suppressor gene, inh cyclin dep kinase 4) dysplastic nevi melanoma pancreatic cancer astrocytoma
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
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
Familial Chronic Mucocutaneous Candidiasis
recurrent progressive candidiasis - skin, nails, mucosa
can look ichthyotic
assoc with APECED and endocrinopathies
they do not get systemic candidiasis
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
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
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
SCID
XLR - IL2 receptor gamma chain (IL2RG)
AR - JAK2 or adenosine deaminase
severe humoral and cellular immunity
def or total abs of lymphocytes
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
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)
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
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
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
OCA Type 4
MATP - melanosome membrane transporter
white/japanese (rare)
looks like OCA2
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
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
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
Elejalde syndrome
variant of Griscelli with myosin Va mut and severe neurologic issues
no immunodef or HLH
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)
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
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
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
Alezzandrini
autoimmune like vogt-koyanagi?
unilateral degenerative retinitis followed by
bilateral deafness and
UNILATERAL vitiligo and poliosis
Waardenburg Syndrome Type 1
AD
PAX3 (transcription factor)
white forelock, leukoderma, heterochromia iridis
synophorus, dystopia canthorum, broad nasal root
deafness uncommon
Waardenburg Syndrome Type 2 (tietz syndorme)
AD
MITF (txn factor)
forelock, leukoderma, heterochromic iridis
deafness common
Waardenburg Syndrome Type 3
AD
PAX3
forelock, leukoderma, heterochromic iridis
upper limb abn (hypoplasia, syndactyly, flexion contractures)
rare neural tube defects
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
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)
Russell-Silver Syndrome
triangular facies short stature hemihypertrophy clinodactyly of 5th finger syndactyly of 2nd/3rd toes precocious puberty cryptorchidism/hypospadius
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
Bonnet-Dechaune-Blanc syndrome (aka Wyburn-Mason)
facial PWS + ipsilateral cranial and retinal AVMs
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
CM-AVM syndrome
AD RASA1 mutation congenitaal and acquired PWS increased incidence of AVMs inc intracranial and spinal AVMs can rupture
parkes Weber (KT-Weber)
multiple AVMs with hypertrophy
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
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)
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
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
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
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
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
Cornelia De Lange Syndrome
sporadic sometimes AD NIPBL (nipped beta like gene) cutis marmorata synophorys trichomegaly craniofacial abn clinodactyly MR, deafness, low-pitched cry
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)
Hereditary Lymphedema (Milroy Disease)
AD FLT4 mut - encodes VEGF receptor 3 (tyr kinase R in lymph vessels) congenital lymphedema chylous ascites cystic higroma
Lymphedema-distichiasis syndrome
AD FOXC2 mut, encodes txn factor late-onset lymphedema double row of eyelashes (distichiasis) trichiasis (eyelashes grow towards eyeball)
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
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)
Meige Lymphedema (Hereditary Lymphedema II)
late onset around puberty
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
Blue Sclera differential
Alkaptonuria Down's syndrome EDS Marfans OI Nevus of Ota Fanconi's PXE "All DEMONs Fly Past"
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
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
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
EDS Kyphoscoliosis (VI)
AR PLOD (lysyl hydroxylase) rare *kyphoscoliosis congenital resp problems muscle weakness joint laxity *ocular fragility (glaucoma, retinal detachment) osteopenia
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
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)
EDS type IX
reclassified as occipital horn syndrome allelic with Menkes (ATP7A, lysyl oxidase defect) exostosis from occipital horn elbow deformity radial head dislocation
EDS type XI
reclassified as familial joint hyper mobility syndrome (new type X)
EDS V
XLR
hyper extensible skin
orthopedic abn
bruising
EDS VIII (periodontal type)
AD
*periodontitis
EDS I/II findings
EDS X
fibronectin def
bruising
joint hypermobility
EDS cardiac valvular
AR
Collagen I (alpha 2 chain)
heart valve defects
EDS I findings
EDS progeroid
AR B4GALT7 (galactosyl transferase I) porgeroid facies osteopenia MR growth retardation skin hyper extensibility joint hyper mobility
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
marfanoid habitus ddx
Marfans Homocysteinuria MEN IIB Klinefelters Congenital Contractural Arachnodactyly Kallman Loey-Dietz
Loeys Dietz
AD TGFBR1 or TGFB2R hyperextensible joints soft velvety skin arterial tortuosity and widespread vascular aneurysm and dissection
Homocysteinuria
AR cystathionine B synthase ectopia lentis (downward) marfanoid habitus *mental retardation DVTs Malar flush Leg ulcers Livedoreticularis Myopia Glaucoma
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)
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)
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
Congenital Contractural Arachnodactyly
AD fibrillin 2 *crumpled ears long limbs arachnodactyly
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
Van Allen Myhre syndrome
severe form of Goltz with lobster hand and foot deformity
Berardinelli-Seip Congenital Lipodystrophy (Congenital generalized lipodystrophy )
BSCL2 gene mutation (nuclear lamins) generalized lipodystrophy Acanthosis nigricans HL DM hepatomegaly
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
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
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
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
Beare-stevenson Cutis Gyrata Syndrome
FGFR2 gene cutis gyrata AN anogenital anomalies craniosynostosis furrowed palms/soles natal teeth
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
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
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
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
Tricho-dento-osseous syndrome
AD DLX3 homeobox gene curly/kinky hair at birth (may straighten after puberty) dental pits inc bone density
Bjornstadt syndrome
AR
pili torti
deafness
nl intelligence and lifespan
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
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
Nevoid Localized Hypertrichosis
anterior cervical hypertrichosis
localized patch of hair
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
Papular Atrichia
AR
human homolog of mouse hairless gene mut
loss of natal hair with subsequent generalized atrichia
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
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
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)
natal teeth (already present at birth)
Pretty Happy Baby
PC
Hallerman-Steife
Baer-sTevens
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
pityriasis rotunda
rare variant of acquired ichthyosis
brown round scaly patches on trunk/ext
japanese, african, west indian
tx resistant unless underlying condition txd
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)
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
Kallman syndrome
XLI MR hypogonadism anosmia continguous gene nut with XLI
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
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
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
bathing suit ichthyosis
AR
TGM1 mut
collodion
bathing suit distribution 2/2 temp sens
self healing collodion
AR
TGM1
variant of LI
collodion but heals in dry environment 2/2 hydrostatic sens TGM1 mut
ARCIs
AR CIE LI Harlequin bathing suit self healing collodion
keratinopathic ichthyoses
AD
superificial epidermolytic ichthyosis (Siemens)
epidermolytic ichthyosis (BCIE)
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)
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
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
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”
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
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
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
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
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
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
Infantile Refsum
PEX1, PEX2, or PEX26
Onset at birth
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
Non-epidermolytic PPK ( unna thost syndrome)
AD Keratin 1 Diffuse with erythematous border Hyperhidrosis Secondary tinea infections Pitted keratolysis No transgradie
Epidermolytic PPK (Vorner Syndrome)
AD
K1 or K9
Epidermolytic
Histo shows epidermolytic HK
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
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
Vohwinkel variant
AD
Loricrin (cornified envelope protein)
mutilating keratoderma + generalized ichthyosis
no deafness
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
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)
Naxos Disease
AR JUP gene - Plakoglobin PPK+ wooly hair + cardiomyopathy (r sided) arrythmias We Are NPR
Carvajal Syndrome
AR
desmoplakin
PPK (first year of life, striate not diffuse) +wooly hair + L sided cardiomyopathy (dilated)
“LCD”
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
nonepidermolytic PPK with deafness
connexin 26 or A7445G (mitochondrial)
PPK + sensorineural deafness
Bart-Pumphrey
AD
GJB2 - connexin 26
PPK with knuckle pads, leukonychia, deafness
Keratoderma climactericum
scaly keratotic soles of feet in post menopausal women
Howel-Evans Syndrome
AD TOC gene (tylosis-oesophageal carcinoma) focal PPK over pressure areas (balls of feet > hands) oral leukokeratosis r/o esophageal cancer
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
punctate PPK (keratosis punctata palmaris et plantaris)
AD
begins during adolescence
punctate keratoses on palms
palmar creases of African origin pts
Acrokeratoelastoidosis
AD
skin-colored papules inv hands and feet
adolescence
striate PPK
AD desmoglein 1 and desmoplakin 1 onset in childhood HK linear plaques on volar fingers diffuse /focal plaques on proximal palms/soles
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
Progressive Symmetric Erythrokeratoderma
AD
loricrin or connexin 31
fixed hyperkeratotic erythematous plaques over joints/extremities
50% with PPK
hidrotic ectodermal dysplasia (Clouston syn)
AD GJB6 (connexin 30) hypotrichosis diffuse PPK *nail dystrophy *normal teeth and sweating MR ocular abnormalities
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
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
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
rapp-hodgkin syndrome
AD p63 mid facial hypoplasia cleft lip/palate scalp dermatitis dec sweating nail dystrophy hypodontia
Ectodermal dysplasia/skin fragility syndrome
AR plakophilin-1 trauma-induced bullae (infancy) sparse hair thick dystrophic nails
whitkop tooth and nail syndrome (trichodental syndrome)
AD MSX1 rare hypodontia (conical and narrow crowns) spoon nails
ADULT syndrome
acral, dermato, ungual, lacrimal tooth syndrome
ectodermal dysplasia with nl sweating
EDA mutation
Schopf-Schulz Passarge
AR
WNT10A - cutaneous signaling molecule involved in ectodermal appendageal development
hydrocystomas of eyelids
hypotrichosis
hypodontia
nail dystrophy
multiple palmoplantar eccrine syringofibroadenomas
Naegeli–Franceschetti–Jadassohn syndrome
diffuse NEPPK KRT14 abnormal sweating reticulate hyperpigmentation absence of dermatoglyphics other ectodermal anomalies
dermatopathia pigmentosa reticularis
diffuse NEPPK KRT14 abnormal sweating reticulate hyperpigmentation absence of dermatoglyphics other ectodermal anomalies
Huriez Syndrome
AD PPK + scleroatrophy - pseudosclerodermatous appearance reticulate erythema dorsal hands no raynauds r/o SCC of palms/soles
Micali syndrome
PPK + scleroatrophy
R spondin 1
alkaptonuria
AR homgentistic acid oxidase blue-gray pigmentation of cartilage (ear helix), sclera and skin (axilla) urine darkens on standing arthritis
biotinidase def
AR alopecia periorificial dermatitis developmental delay seizures treat with biotin
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
fucosidosis
AR alpha-fucosidase mult angiokeratomas coarse facies growth retardation dysostosis multiplex - severe abnormalities in development of skeletal cartilage and bone MR
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
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
Holocarboxylase synthestase def
AR alopecia perioral/perianal dermatitis metabolic encephalopathy metabolic acidosis treat with biotin
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
hurler disease
AR alpha-L iduronidase ( L = hurLer) MR HSM hernia opacities gargoyle like features extensive dermal melanocytosis
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
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
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
Rombo syndrome
XLD Hypotrichosis - pili torti milia trichoepitheliomas vellus hair cysts BCC photosensitivity atrophoderma vermiculata (limited to cheeks, looks like acne scars, honeycomb appearance)
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
Kleinfelters
XXY
tall stature with long limbs
Reduced body hair
LE varicosities with recurrent leg ulcers
Wilson’s disease
Retention of copper
Greenish discoloration of face, neck, genitalia
Blue lunulae of the nails
Kayser fleischer rings
Hemochromatosis
AR Increased intestinal iron absorption Metallic gray hyper pigmentation Koilonychia Sparse hair Hypoganadism Arthritis Hepatomegaly Cardiac fx and arrx
Ichthyosis with confetti
KRT10
Sporadic
frameshifts mut - arginine-rich C-terminal peptide that redirects keratin 10 from the cytokeratin filament network to the nucleolus
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)
phenylketonuria
AR SLC39A4 (zinc transporter) diffuse hypopig eczema MR sclerodermoid changes blonde hair, blue eyes urine and skin with mousy odor
prolidase deficiency
AR prolidase skin fragility ulceration and scarring LEs photosens MR recurrent infxn
wilson’s disease
AR ATP7B (ATPase copper transporting enzyme) copper accumulation in liver/brain/cornea cirrhosis blue lunula kayser Fleischer rings ataxia dementia hepatomegaly
RAS-ERK-MAPK pathway
include: Cardio-facio-cutaneous syndrome, Costello, LEOPARD, NF, and Noonan
Brooke speigler
CYLD gene
Cylindromas
Trichoepitheliomas
