Profillagrin (decreased in keratinocytes) 

AD

likely polygenic

STS (steroid sulfatase gene)

steroid sulfatase deficiency=increased cholesterol sulfate and decreased cholesterol in stratum corneum

failure of progression of labor (due to increased fetal placental sulfatase and increased fetal DHEA)

brown adherent scales (spares palms/soles/face/flexures)

comma shaped corneal opacities

cryptorchidism

Labs: inreased serum cholesterol sulfate

What is another name for Epidermolytic Hyperkeratosis?

K1/K10

(defective keratin leads to tonofilament clumping and bullae formation)

(ichthyosis hystrix, with extensive epidermal nevi reflects a somatic mosaicism for K1/K10)

AD (50% spontaneous)

widespread bullae; denuded skin; secondary sepsis; elecrolyte imbalance ; +/- focal hyperkeratosis 

later: generalized hyperkeratosis, rare focal bullae, dark warty scales with spiny ridges (corrugated pattern), secondary bacterial in intertriginous areas,  PPK in some, nail dystrophy, scales shed with full thickness stratum corneum leaving tender denuded base

AR

TGM1; transglutaminase 1

heterogeneous mutations in TGM1 interfere with normal cross linking of structural proteins in protein and lipid envelope

Lamellar Ichthyosis

Dx with skin biopsy for in-situ detection of transglutaminase-1 expression and activity; Mutations in the ABCA12 gene, less severe than those seen with harlequin ichthyosis

Dx: collodion baby, generalized erythroderma with fine white scale, flexures involved; extensor legs with large platelike dark scale; +/- PPK; hypohidrosis with heat intolerance?

Congenital Ichthyosiform Erythroderma (CIE)

TGM1 in some, different gene loci in others

ABCA12

ABCA12 activity is required for the generation of long-chain ceramide esters that are essential for the development of normal skin structure and function

Sjogren-Larsson Syndrome

AR, Fatty aldehyde dehydrogenase (FALDH gene) lead to decrease in fatty alchohol:NAD oxidoreductase with defective conversion of fatty alcohol to fatty acid (important for epidermal lipids and phospholipids/sphingolipids in CNS myelin)

accumulated fatty alcohol/fatty aldehyde/leukotriene B4=pruritus

Sjogren-Larsson syndrome (AR)

generalized ichthyosis, MR, spastic tetraplegia (scissor gait), "glistening white perimacular dots"

PEX7=peroxin 7 (enzymes to peroxisomes)

PAHX=phytanoyl-CoA hydroxylase (catalyzation of phytanic acid)

Refsum Syndrome (a.k.a. Phytanic acid storage disease)

AR

PAHX on 10p/PEX7 on 6q

dietary treatment with a phytanic acid-restricted diet, such as exclusively avoiding green plants and to a lesser extent, consumption of fatty animal tissues from beef, lamb, and fatty fish such as tuna, cod, and haddock

X-linked dominant chondrodysplasia punctata; Conradi-Hunermann-Happle syndrome

usually lethal in males

Conradi-Hunermann-(Happle) syndrome; X-linked dominant chondrodysplasia punctata

EBP gene/emopamil-binding protein = defect in cholesterol biosynthesis

CHILD Syndrome

Congenital hemidysplasia with ichthyosiform erythroderma and limb defects

CHILD

congenital hemidysplasia with ichthyosisform erythroderma and limb defects

X-linked dominant; NSDHL (affecting cholesterol biosynthesis)

Ichthyosis linearis circumflexa (ILC), a.k.a. Netherton syndrome

AR, SPINK5 gene encodes LEKT1 (serine protease inhibitor important in downregulating inflammatory pathways and possibly related to atopy).

Netherton Syndrome

ILC (ichthyosis linearis circumflexa)

SPINK5/LEKT1 (serine protease inhibitor)

Erythrokeratoderma Variabilis (EKV)

AD, GJB3 (connexin 31) GJB4 (connexin 30.3)

Erythrokeratoderma Variabilis (Mendes da Costa)

AD, GJB3 (connexin 31) GJB4 (connexin 30.3)

treat with oral retinoids (low dose)

GJB3 connexin 31

GJB4 connexin 30.3

GJB2 (connexin 26)

gap junction protein responsible for intercellular communications in the epidermis and cochlea

KID (keratitis-ichthyosis-deafness)

AD, GJB2 (connexin 26)

Vorner PPK or epidermolyitic PPK

Unna-Thost PPK or non-epidermolytic PPK

diffuse PPK

either Vorner (epidermolytic) or Unna-Thost (nonepidermolytic)

Howel-Evans Syndrome

tylosis and oesophageal cancer (TOC) gene on 17q25

Howel-Evans Syndrome

AD, TOC gene (tylosis and oesophageal cancer)

referral to GI

KID or Vohwinkel

encodes connexin 26

Vohwinkel Syndrome (PPK mutilans, Keratoderma hereditaria mutilans)

AD

classic (w/ deafness): GJB2 (connexin 26)

Loricrin variant: loricrin gene on EDC (epidermal differentiation complex) 1q21

Mal de Maleda (Keratoderma palmoplantaris transgrediens)

AR

SLURP1 (secreted Ly-6/uPar related protein 1) encodes for proteins important in cell signaling and adhesion

Mal de Maleda

SLURP1 gene

AR

Papillon-Lefevre Syndrome

AR

CTSC encodes for cathepsin C, a lysosomal protease

Papillon-Lefevre Syndrome (Palmoplantar keratoderma with periodontosis)

AR, CTSC

Tyrosinemia type II

AR, tyrosine aminotransferase gene 16q22.1-q22

Richner-Hanhart Syndrome (tyrosinemia type II)

AR, tyrosine aminotransferase gene

Lab: increased plasma and urinary tyrosine levels (and metabolites)

Refer to ophthalmologist

Darier's disease (Keratosis follicularis)

AD, ATP2A2 encoding SERCA2 a Ca2+ pump providing increased extracellular Calcium necessary for normal epidermal differentiation and formation

Darier's disease (dyskeratosis follicularis)

AD, ATP2A2 encoding SERCA2 (calcium pump)

Tx with systemtic retinoids, limit direct sunlight (worse in summer)

Epidermal nevus syndrome, Inflammatory linear verrucous epidermal nevus, linear sebaceous nevus

(many distinct genetic diseases all sharing a phenotype reflecting genetic mosaicism)

Ichthyosis hystrix, Curth-Macklin type: hyperkeratosis is brown-grey in colour and is most obvious on the arms and legs. It is a autosomal dominant condition and can be caused by errors to the KRT1 gene

Ichthyosis hystrix, Lambert type:  spiny scales which cover the entire body except the face, genitals, palms and soles. The only known cases were in Edward Lambert (known as the porcupine man) and three generations of his descendants

ILVEN (inflammatory linear verrucous epidermal nevus)

Nevus Unius Laterus

Epidermal Nevus Syndrome

referral to Neurologist, ophthalmologis, orthopedist

Genetic counseling if at risk for EHK (BCIE) offspring

Oculocutaneous Albinism Type I (OCA1)AR, tyrosinase gene (TYR) 11q14-q21 

"tyrosine negative albinism" 

absent tyrosinase activity, i.e. lack of tyrosinase transport to melanosomes (normal # melanocytes, unable to produce melanin in skin/hair/eyes)

OCA1 (oculocutaneous albinism type 1)

"tyrosinase negative albinism"

TYR gene, AR

OCA2 (oculocutaneous albinism type II)

tyrosinase positive albinism

AR, P gene mutation leading to decrease eumelanin synthesis; decreased melanin in skin/hair/eyes

OCA2

"tyrosine positive albinism"

AR, P gene

Hermansky-Pudlak Syndrome

AR, HPS1 gene; AP3B1 gene (+5 others)

HPS1 gene duplication of gene for protein localization via intracellular trafficking and organelle formation.

AP3B1 gene cause HPS2 important in protein packaging

"tyrosinase positive"

Hermansky-Pudlak Syndrome

HPS1 mutation, AR

Avoid aspirin (and other PG synthesis inhibitors)

baseline chest x-ray/PFTs/colonoscopy (if s/s)

premature death secondary to hemorrhage/colitis/pulmonic

Hermansky-Pudlak Syndrome

HPS1 or AP3B1

Chediak-Higashi Syndrome

AR, LYST coding for lysosomal tracking protein regulating microtubule mediated lysosomal fusion/fission and protein sorting (leads to accumulation of giant lysosomal granules in Neuts/Melanocytes/Neurons)

Chediak-Higashi Syndrome

AR, LYST gene on 1q42 encoding for lysosomal tracking protein regulating microtubule mediated lysosomal fusion/fission (leads to accumulation of giant lysosomal granules in Neuts/Melanocytes/Neurons), platelet storage pool deficiency=bleeding diathesis, decreased NK cell and antibody cell-mediated cytolysis function=frequent bacterial infxn

Tx: bone marrow transplant, high dose ascorbic acid (death by 10)

Griscelli Syndrome

AR, myosin Va or RAB27a are proteins involved in organelle trafficking and membrane transport; melanophilin gene mutations also implicated

Griscelli Syndrome

AR, myosin Va or RAB27a (MYO5A gene)

Lab: clusters of melanin on hair shaft/medulla

Tx: BMT

Piebaldism

AD, mutation in c-kit proto-oncogene on 4q12

c-kit mutation results in abnormal tyrosine kinase transmembrane receptors, decreases signal transduction, and causes abnormal melanocyte embryogenesis with defective melanoblast proliferation, migration and distribution

Piebaldism (familial white spotting)

AD, c-kit proto-oncogene mutation

Type I: PAX3

Type II: MITF

Type III: PAX3

Type IV: SOX10 and endothelin-3

Waardenburg Syndrome

AD

Type I and III: PAX3, transcription factor controlling neural crest differentiation

Type II: MITF, melanocyte transcription factor

Type IV: SOX10 and endothelin-3

Dystopia canthorum= inner canthal distance/outer canthal distance > 0.6. 

Incontinentia Pigmenti (Bloch-Sulzberger syndrome)

X-linked dominant, NEMO (NF-kappaB modulator) codes for NF-kappa B a transcription factor essential for several inflammatory, immune and apoptotic pathways. 

I: vesicular (birth to 1-2 weeks)

II: verrucous (2-6 weeks)

III: hyperpigmentation (3-6 months)

IV: hypopigmentation (second to third decade)

Incontinentia Pigmenti (a.k.a. Bloch-Sulzberger syndrome)

NEMO gene (NF-kappaB essential modulator)

LEOPARD Syndrome (multiple lentigines syndrome)

AD, PTPN11 encodes nonreceptor protein tyrosine phosphatase SHP2

LEOPARD Syndrome (multiple lentigines syndrome)

AD, PTPN11 gene

L: Lentigines

E: ECG conduction defects

O: Ocular hypertelorism

P: Pulmonic stenosis

A: Abnormal genitalia

R: growth Retardation

D: sensorineural Deafness

Carney Complex (NAME syndrome, LAMB syndrome)

AD, PRKAR1A gene, tumor suppressor gene

lentigines, blue nevi, melanocytic nevi, ephelides, myxomas (including atrial)

Carney complex (NAME, LAMB syndrome), PRKAR1A gene

N: Nevi

A: Atrial myxomas

M: myxomas

E: Ephelides

Refer to Cardiologist, endocrinologist

McCune-Albright Syndrome

sporadic, postzygotic somatic mutation in GNAS1 encoding for the alpha subunit of the stimulatory G proteins that regulates adenylate cyclase

McCune-Albright Syndrome

sporadic post-zygotic somatic mutation of GNAS1 (encoding alpha subunit of stimulatory G proteins regulating adenylate cyclase)

Neurofibromatosis I (von Recklinghausen disease)

AD, NF-1 on 17q11.2 (spontaneous 50%), tumor suppressor that dampens products of ras proto-oncogenes and its loss may contribute to tumor progression when gene mutation occurs

2 or more of:

Six or more cafe au lait macules over 5 mm diameter (pre-pubertal) 15 mm (postpubertal)

2 or more neurofibromas or 1 plexiform neurofibroma

Freckling in axillar/inguinal regions

Optic glioma

Two or mor Lisch nodules

Distinctive osseous lesion (e.g. sphenoid dysplasia, thinning of long bone cortex +-pseudoarthrosis)

First degree relative with NF-1

Neurofibromatosis I (von Recklinghausen disease)

NF-1 17q11.2, tumor suppressor dampens ras proto-oncogenes

Neurofibromatosis II (bilateral acoustic neurofibromatosis; central neurofibromatosis)

AD, SCH gene (spontaneous 50%)

neurofibromas, bilateral acoustic neuromas (vestibular schwannomas), schwannomas of other cranial nerves, meningiomas, astrocytomas, ependymomas

NF2 (bilateral acoustic neurofibromatosis) 

never swim alone!

bilateral 8th nerve masses (CT or MRI) -or-

First degree relative with NF2 -and either-

unilateral 8th nerve mass -or-

any 2: neurofibroma, meningioma, spinal glioma, schwannoma, juvenile posterior subcapsular lenticular opacity

Tuberous Sclerosis (Bourneville's syndrome; epiloia)

AD, TSC1 or TSC2 (66% spontaneous mutations)

TSC1: hamartin

TSC2: tuberin tumor suppression and interact to regulate GTPase activity of rap 1 GAP family genes.  TSC2 with renal cysts may be associated with deletion in contiguous polycystic kidney gene

Tuberous sclerosis (Bourneville's syndrome; epiloia)

TSC1 (hamartin) and TSC2 (tuberin) interact to regulate GTPase ativity of rap 1 GAP family genes

Sturge-Weber Syndrome (encephalotrigeminal angiomatosis)

sporadic, likely autosomal lethal mutation surviving by mosaicism

Sturge-Weber Syndrome (encephalotrigeminal angiomatosis)

MRI, PET/SPECT, EEG

refer to Neurology, ophthalmology, oral surgeon

Klippel-Trenaunay Syndrome (angio-osteohypertrophy syndrome)

sporadic

Tx: compression wraps, stockings, pump; refer to Ortho, Vascular surgeon, laser

Cobb syndrome (cutaneomeningospinal angiomatosis)

sporadic, rare spinal AVM, more common without skin involvement

refer to Neurology and Neurosurgery after MRI/MRA

Proteus

(possibly includes Riley-Smith and Bannayan syndromes)

sporadic

Proteus Syndrome

sporadic mosaicism for PTEN mutation

"Elephant Man" Joseph Merrick

Beckwith-Wiedemann Syndrome (exomphalos-macroglossia-gigantism, i.e. EMG syndrome)

sporadic mutation in p57 (KIP2), a cyclin-dependent kinase inhibitor acting as a negative regulator of cell proliferation, leads to overgrowth of organs and increased susceptibility to malignancies

Beckwith-Wiedemann Syndrome

sporadic mutation of p57 (KIP2) gene a cyclin dpendent kinase inhibitor gene

important to control hypoglycemia in neonate (to maintain normal intelligence).

Von Hippel-Lindau Syndrome

AD, VHL gene (tumor suppressor)

Von Hippel-Lindau Syndrome

AD, VHL gene (tumor suppressor)

CT/MRI brain and spinal cord, abdomen

Urinary vanillylmandelic acid (VMA) level screen

Serum catecholamine level screen

CBC

Ataxia-Telangietasia

AR, ATM gene coding for DNA repair (esp. after ionizing radiation) via p53 dependent pathway

ataxia presents initially in second or third year of life (telangiectasias by 3-6 yo)

Ataxia-Telangiectasia (Louis-Bar syndrome)

ATM gene, AR, codes for DNA repair via p53 dependent mechanism

avoid x-rays, radiotherapy, bleomycin

refer to heme/onc, pulmonologist, neurologist

Hereditary Hemorrhagic Telangiectasia Syndrome (Osler-Weber-Rendu Syndrome)

AD, HHT1, endoglin gene a transforming growth factor (TGF-beta) binding protein on endothelial cells essential for angiogenesis

AD, HHT2, ALK1 gene expressed on endothelial cells

HHT (Osler-Weber-Rendu syndrome)

HHT1 and HHT 2 mutations

Hereditary Hemorrhagic Telangiectasia (HHT)

a.k.a. Osler-Weber-Rendu Syndrome

HHT1, endolin gene mutation (increased pulmonary AV fistula)

HHT2, ALK1 gene mutation (increased hepatic AVMs)

AD

refer to Oto, GI, Thoracic surgeon

Dx: atrophic reticulated vascular patches on extremities>trunk>face; localized segmental or generalized with rare ulceration; phlebectasias, capillary malformation

Associated 50%: ipsilateral hemiatrophy/hemihypertophy of extremity; patent ductus arteriosus, arterial stenosis; glaucoma; MR

Cutis Marmorata Telangiectatica Congenita

sporadic (poss. autosomal lethal mutation surviving in mosaic state)

regular limb length measurements

refer to ophtho for periocular involvement

Maffucci Syndrome

sporadic

venous malformations and skeletal distortion

Ortho

Blue Rubber Bleb Nevus Syndrome

sporadic

special attention to GI bleeding/anemia

Kasabach-Merritt Syndrome

sporadic

consumption coagulopathy within hemangioendothelioma or tufted angioma (20% mortality 2/2 hemorrhage)

Tx: prednisone, vincristine, interferon  (propranolol?)

Diffuse Neonatal Hemangiomatosis (a.k.a. multiple neonatal hemangiomatosis)

sporadic

Tx: prednisone, vincristine, interferon, (propranolol?), hepatic artery ligation/embolization

P: posterior fossa brain malformations

H: Hemangioma (facial)

A: arterial anomaolies

C: cardiac anomalies and aortic coarctation

E: eye abnormalities

S: sternal clefting/supraumbilical raphe

MRI/MRA (posterior fossa malformation)

Aortagraphy/ECG (heart/aorta)

Refer to ophthalmology

PHACES syndrome

sporadic (poss. x-linked dominant as F>M)

often misdiagnosed as Sturge-Weber syndrome

ability to touch nose with tongue tip

alternately ability to touch elbow with tongue

Vascular type (IV) due to risk for arterial and intestinal ruptures, as well as uterine rupture during labor

refer for cardiovascular evaluation with special attention to aortic root and possible aneurysms.

Classical (I and II), AD

Hypermobility (III), AD

 Vascular (IV), AD

Kyphscoliosis (VI), AR

Arthrochalasia (VIIA, VIIB), AD

Dermatosparaxis (VIIC), AR

Others (V, VIII, X, XI)

Classical (types I and II)

AD, mutation in COL5A1 and COL5A2 chains in type V collagen in most patients; deficiency in tenascin X in small number

Vascular type (IV) EDS

AD, COL3A1 mutation results in abnormal synthesis structure and secretion of type III collagen

Arthrochalasia (VIIA and VIIB) type EDS

AD, defective conversion of procollagen to collagen type I

Dermatosparaxis (VIIC) type EDS

AR

severe fragility, laxity with sagging redundancy; easy bruisability, umbilical/inguinal hernias, premature rupture of fetal membranes, normal wound healing

V1 +- V2/V3

Unilateral>>bilateral

progressive soft tissue and skeletal hypertrophy beneath malformation

cerebral atrophy

capillary/venous/arteriovenous malformations in leptomeninges

tram-track calcification in temporal and occipital cortex

seizures >70%, intellectual impairment, hemiparesis, HA

choroid malformation

glaucoma, secondary buphthalmos, visual loss

MRI or CT head (with contrast)

if <6 months, PET/SPECT

EEG (if above positive)

Sporadic

M>F

doppler ultrasound

MRI/MRA

venography

lymphography

compression

leg measurement (ortho for discrepancy)

vascular surgeon (varicosities/AV fistulas)

PDL to capillary malformation

fast-flow vascular malformation within intramedullary spinal cord with secondary compression

anoxia, pain, weakness, mm. atrophy, sensation loss below level of compression;

bladder/sphincter dysfunction;

subarachnoid hemorrhage

MRI/MRA

spinal angiography

tx: extirpation of lesion v. embolization by neurosurgery

Mutations in collagen type I?

i.e. COL1A1 (type A) or COL1A2 (type B)

Arthrochalasia type EDS

defective conversion of procollagen to collagen type I

Dermatosparaxis type EDS

AR

Vascular (previously type IV)

AD

mutation in COL3A1, i.e. type III collagen

Kyphoscoliosis (previously type VI)

AR

mutation in PLOD (procollagen lysyl 2oxoglutarate 5 dioxygenase)

Hypermobility type (previously type III)

AD

? pathogenesis/mutation

recurrent dislocations, early onset DJD

(also classical EDS possible delay in ambulation)

hyperextensible skin; "snap back elasticity"

gaping wounds; cigarette paper scars

molluscoid pseudotumors; calcified subq nodules

varicose veins; eccyhmoses

EDS, classical type

AD

COL5A1 and COL5A2, i.e. type V collagen (50%)

OR

tenascin X (3% patients)

Arthrochalasia

type I collagen

AD

Blue sclerae

ruptured globe

retinal detachment

keratoconus

atrophic reticulated vascular patch

MR

glaucoma

PDA/arterial stenosis

Cutis Marmorata Telangiectatica Congenita

sporadic inheritance

superficial/deep venous malformations (predominantley hands/feet)

enchondromas

short stature

chondrosarcoma (15%-20%)

Maffucci Syndrome

sporadic, about 100 case reports

Blue Rubber Bleb Nevus Syndrome

also with venous malformations of small intestine and secondary hemorrhage (+anemia)

endoscopy

MRI (GI)

CBC

stool guaiac

excision/CO2 laser

GI screening

anemia tx (iron/tranfusions/endoscopic cautery/bowel resect)

Kasabach-Merritt Syndrome

sporadic, about 175 case reports

CBC

PT/aPTT

fibrinogen (decreased)

fibrin degradation products (increased)

prednisone

vincristine

Interferon-alpha

Hematology: transfusions/infusions of fibrinogen or FFP +- plts)

propranolol?

Diffuse Neonatal Hemangiomatosis

sporadic

a.k.a. multiple neonatal hemangiomatosis or benign neonatal hemangiomatosis

hemangiomas in any organ

hepatomegaly; obstructive jaundice; portal hypertension;

hemorrhage; thrombocytopenia; anemia; high output CHF

skin biopsy

liver u/s

CT/MRI (head/chest/abdomen)

CBC/coag studies

stool guaiacs

urinalysis (hematuria)

progressive aneurysmal dilatation of ascending aorta, with secondary regurgitation

CHF, dissection and rupture

MV prolapse

upward displacement (75%) i.e. ectopia lentis

myopia

tall stature, lower body length longer than upper body

arachnodactyly

dolichocephaly

pectus excavatum

high arched palate

loose joints

poor mm tone

kyphoscoliosis; pes planus; inguinal hernia

Marfan syndrome

AD

fibrillin-1 mutation

AR, FBLN5 (fibulin 5)

AD, elastin gene and FBLN5

X-linked recessive, ATP7A

Cutis laxa (generalized elastolysis)

can also be aquired

vocal cord laxity (deep resonant voice)

hypoplastic lungs (birth); emphysema

esophageal/duodenal/rectal diverticulae

bladder diverticulae

inguinal/diaphragmatic/umbilical hernia

hip dislocation

occipital horn exostoses (x-linked)

biopsy: decreased, fragmented elastic fibers visualized with Verhoeff-van Gieson stain

serum copper and ceruloplasmin levels

CXR

Bloom syndrome

Rothmund-Thompson syndrome

PIBIDS (trichothiodystrophy)

Cockayne syndrome

Hartnup disease

Trichothiodystrophy (PIBIDS)

photosensitivity, ichthyosis, brittle hair, intellectual impairment, decreased fertility, short stature

Bloom syndrome

AR, RecQL3 helicase for DNA helicase

decreased IgA, IgM, +-IgG with recurrent respiratory and GI infections

20% with ALL, lymphoma, GI adenocarcinoma (most common)

Poikiloderma congenitale

AR, RecQL4 helicase

Rothmund-Thompson (poikiloderma congenitale)

AR, RecQL4 helicase

Cockayne syndrome

AR, ERCC8 and ERCC6 (impairs DNA repair in  active genes)

Cockayne syndrome

AR, ERCC8 and ERCC6

Trichothiodystrophy (PIBIDS)

AR, ERCC2 

heterogeneous group of neuroectodermal disorders all sharing sulfur-deficient brittle hair

high nutritional standards offset lack of absorption

in Africa you'll see kids "reeling around"

urine for aminoaciduria and tryptophan derivatives 

Hartnup disease

Bloom syndrome

Cockayne syndrome

Pellagra

Lupus erythematosus

Erythropoietic protoporphyria (EPP)

Ehlers-Danlos

Marfan syndrome

Cutis Laxa

Pseudoxanthoma elasticum

Osteogenesis imperfecta

Buschke-Ollendorf syndrome

Focal dermal hypoplasia

Lipoid proteinosis

Progeria

Werner syndrome

Aplasia cutis congenita

Ichthyosis vulgaris

X-linked icthyosis (steroid sulfatase deficiency)

Epidermolytic hyperkeratosis (BCIE)

Lamellar ichthyosis

Congenital ichthyosiform erythroderma

Harlequin fetus

Sjogren-Larsson syndrome

Refsum syndrome (phytanic acid storage disease)

Conradi-Hunermann syndrome (XD chondrodysplasia punctata)

CHILD syndrome

Netherton syndrome (ichthyosis linearis circumflexa)

Erythrokeratoderma Variabilis (Mendes da Costa)

KID syndrome

Diffuse PPK (Vorner and Unna-Thost)

Howel-Evans Syndrome

Vohwinkel syndrome (PPK mutilans)

Mal de Maleda (keratoderma palmoplantaris trangrediens)

Papillon-Lefevre (PPK with periodontosis)

Richner-Hanhart (tyrosinemia)

Darier disease (keratosis follicularis)

Epidermal nevus syndrome (ichthyosis histrix/ILVEN)

Oculocutaneous albinism type I (OCA1)

Oculocutaneous albinism type II (OCA2)

Hermansky-Pudlak syndrome

Chediak-Higashi syndrome

Griscelli syndrome

Piebaldism

Waardenburg syndrome

Hypomelanosis of Ito

Incontinentia pigmenti

LEOPARD syndrome

Carney Complex

McCune-Albright syndrome

Neurofibromatosis I

Neurofibromatosis II

Tuberous sclerosis

Sturge-Weber

Klippel-Trenaunay

Cobb syndrome

Proteus syndrome

Beckwith-Wiedemann

Von Hippel-Lindau

Ataxia telangiectasia

Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu)

Cutis Marmorata Telangiectatica Congenita

Maffucci syndrome

Blue Rubber Bleb Nevus syndrome

Kasabach-Merritt

Diffuse neonatal hemangiomatosis

PHACE syndrome

Basal cell nevus syndrome (Gorlin syndrome)

Xeroderma pigmentosum

Muir-Torre

Dyskeratosis congenita

Gardner syndrome

Peutz-Jeghers

Cowden syndrome

Multiple endocrine neoplasia type IIB

Birt-Hogg-Dube

Wiskott-Aldrich

Chronic granulomatous disease

Hyper-IgE

Severe Combined Immunodeficiency

Hereditary angioedema

Menkes

Bjornstad

Argininosuccinic aciduria

Monilethrix

Uncombable hair syndrome

hypohidrotic ectodermal dysplasia

Hidrotic ectodermal dysplasia

EEC syndrome

AEC syndrome

Pachyonychia congenita

Nail-patella syndrome

Alkaptonuria (ochronosis)

Fabry disease (angiokeratoma corporis diffusum)

Gaucher disease

Niemann-Pick

Mucopolysaccharidoses =  (Hurler/Hunter/Sheie/Sanfilippo/Morquio/Maroteaux-Lamy)

Multiple carboxylase deficiency (biotinidasse deficiency)

phenylketonuria

Wilson's disease (hepatolenticular degeneration)

Acrodermatitis enteropathica

Hemochromatosis

Homocystinuria

Hyperlipoproteinemias (types I-V)

Down syndrome (trisomy 21)

Turner (gonadal dysgenesis)

Noonan

Klinefelter

Cornelia de Lange

Rubinstein-Taybi

Russel-Silver

Familial dysautonomia (Riley-Day)

Ichthyosis vulgaris

progressive symmetric erythrokeratoderma

Vohwinkel (loricrin variant)

various ichthyoses (CHILD/Conradi-Hunermann-Happle/ neutral lipid storage disease, CIE, Refsum, rhizomelic chondrodysplasia punctata, Sjogren-Larsson, X-linked ichtyosis)

hyperlipidemias

Farber lipogranulomatosis

Gaucher disease (type 2)

hyper IgD with periodic fever

Mari-type hypotrichosis

Neimann-Pick

lamellar ichthyosis

CIE

acral peeling skin syndrome

Pseudoxanthoma Elasticum (PXE)

AR and AD (less common), ABCC6

yellow papules on labial mucosa/soft palate/rectal and vaginal mucosa

angiod streaks(i.e. rupture in Bruch's membrane)

gastric artery hemmorhage with epistaxis

increase 1st trimester miscarriage

PXE

AR (sometimes AD), ABCC6

blindness is a serious concern (although total blindess is rare)

MI and GI hemmorhages are major life threateners

heterogeneous mutations in genes encoding type I collagen

easy bruising/decreased skin elasticity

hearing loss (otosclerosis)

dentinogenesis imperfecta

MVP

Osteogenesis Imperfecta

AD (some II and III are AR)

also w/ blue sclerae, fractures, crippling bone deformities, bowing, kypophoscoliosis, joint laxity

skin colored to yellow dermal papules w/wo coalesced plaques often with symmetric distribution on trunk/buttock/arms

Osteopoikilosis (1- 10 mm welll circumscribed round to oval opacities within carpal, tarsal bones, long bones (asymptomatic xray finding)

Buschke-Ollendorff Syndrome 

dermatosfibrosis lenticularis disseminata

Hair: sparse/brittle/patchy alopecia

Nails: absent or dystrophic

Eyes: coloboma/strabismus/microphthalmia

MS: syndactyly/polydactyly/oligodactyly (w/lobsterclaw) asymmetric trunk/limbs, osteopathia striata

Oral: hypodontia, oligodontia, small teeth

Craniofacial: small, rounded asymmetric face, notched nasal alae, mandibular prognathism

CNS: MR (mild)

Urbach-Wiethe disease 

hyalinosis cutis et mucosae

lipoid proteinosis 

hyalinosis cutis et mucosae

Lipoid proteinosis (Urbach-Wieth disease) 

AR

bullae with residual atrophic scarring face/extremities/neck

yellow papules/nodules on face/neck with "string of pearls"

verrucous nodules on elbows/knees/hands

Lipoid proteinosis (Urbach-Wiethe disease) 

hyalinosis cutis et mucosae

patchy alopecia (scalp/beard/eyelashes)

infiltrative yellow papules and plaques on pharynx/lips/soft palate

hoarse cry (vocal cord infiltration)

large wooden tongue

temporal/hippocampal calcification +/- seizures

thin atrophic shiny skin with wrinkles; prominent scalp and thigh veins, loss of sq fat, mottled hyperpigmentation, sclerodermoid changes on lower grunk and thigh

large cranium relative to face

large cranium; frontal bossing; thin beaked nose; small ears without lobules; micrognathia; prominent eyes

failure to thrive, short stature, osteoporosis

premature severe atherosclerosis with angina; high pitched squeaky voice; CVA, CHF, MI; abnormal or delayed eruption of permanent teeth;

severe psychosocial issues related to appearance/self image

AR, RECQL2 gene

(RecQL3 for Bloom syndrome; RecQL4 for Rothmund Thompson syndrome)

bird like facies with beaked pinched nose, taut circumoral skin, inelastic ears

short stature (growth arrest at pube), mm wasting, thin spindly extremities, pes planus, osteoporosis/OA

posterior subcapsular cataracts

high pitched, hoarse voice

premature atherosclerosis c/ angina; MI

DM, hypogonadism

(10%) fibrosarcoma, osteosarcoma, cutaneous carcinoma, meningioma, adenocarcinoma

mutation in RecQL2 (or WRN gene)

encoding a DNA helicase enzyme, leading to increased frequency of recombination with a predisposition toward accelerated aging and cancer

limb abnormalities

epidermal nevi

embryologic malformations

fetus papyraceus/placental infarcts

epidermolysis bullosa

teratogens (methimazole)/intrauterine infection (varicella/HSV)

malformation syndromes (Down, Goltz, aminotic band, Opitz, Adams-Oliver)

infection

hyperthermia

hypoventilation

bone marrow failure at median age of 10

increased cancer risk

pterygium

continuous lacrimation

premalignant leukoplakia

disease associated with:

infection with catalase + organisms

serratia osteomyelitis

shortened life span (even with prophylactic abx)

XLR inheritance

BMT

patients are immunodeficient and pancytopenic

PXE

EDS

Cowden's

idiopathic (50%)

Tuberous sclerosis

NF

Down syndrome

Osteogenesis imperfecta

EDS

PXE

Marfan's

Alkaptonuria

minocycline

PTU

hydralazine