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"
