• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off

Card Range To Study



Play button


Play button




Click to flip

Use LEFT and RIGHT arrow keys to navigate between flashcards;

Use UP and DOWN arrow keys to flip the card;

H to show hint;

A reads text to speech;

324 Cards in this Set

  • Front
  • Back
Eponym for Incontinentia Pigmentosa
Bloch-Sulzbuerger syndrome
Four phases of Incontinentia Pigmentosa
Phase 1: Vesicular (1-2wks old)
Phase 2: Verrucous (2-6wks)
Phase 3: Hyperpigmentation
Phase 4: Hypopigmentation (2nd - 3rd decade)
Other Clinical Findings in Incontinentia Pigmentosa
Scarring Alopecia, Dystrophic changes in Nails, Anodontia or peg/conical teeth, strabismus, CNS - seizures, MR
Gene for Incontinentia Pigmentosa
NEMO, Xlinked.
Only females or Klinefelter's pts have seen to have this disorder.
Conradi-Hunermann Syndrome Eponym?
Chondrodysplasia punctata
How many types of chondrodysplasia puntata are there?
Four -- base on inheritance patterns:
1. Conradi-Hunerman type is AD
2. Rhizomelic form is AR, dies in infancy, Arylsulfatase E gene
3. X-linked recessive, continguous gene deletion syndrome, Arylsulfatase E gene
4. X-linked dominant = EBP gene = Emopamil-binding protein on Xp11
Turner Syndrome Eponym
XO syndrome
Gonadal dysgenesis
Noonan Syndrome Gene defect
PTPN11 gene on Chromosome 12
encodes protein tyrosine phosphatase SHP2 (also in LEOPARD)
LEOPARD Syndrome synonym
Multiple Lentigines Syndrome
Name the Dz:
retinal angiomas
cerbellar medullary angioblastic tumors
pancreatic cysts
renal tumors and cysts
cerebellar hemangioblastomas
secondary polycythemia
Von Hippel-Lindau syndrome
Inheritance and gene mutation in Von Hippel-Lindau syndrome
germline mutation of a tumor suppressor gene on short arm of Chromosome 3
AR, RecQL3 gene

DNA helicase – important in DNA replication and repair

Mutation: sister chromatid exchanges; chromosomal breaks/gaps
Bloom syndrome

Photodistributed erythema with telangiectasias in butterfly distribution
Dz & what other immune problems are assoc with it?
“triangle face” – long narrow face with prominent nose and small mandible
High pitched voice
Low IgA, IgM  Recurrent respiratory/GI infections
Hypogonadism, Infertile males
What Ig are low in Bloom Syndrome?
Low IgA, IgM -->
Recurrent respiratory/GI infections
What syndrome has:
“triangle face” – long narrow face with prominent nose and small mandible
High pitched voice
Hypogonadism, Infertile males
Bloom Syndrome
What neoplasms can be assoc with Bloom Syndrome?
Acute leukemia
GI adenocarcinoma
Another name for Poikiloderma congenitale?
Defect in Rothmund-Thomson
AKA: Poikiloderma congenitale
AR, RecQL4 gene (some cases)
DNA helicase  DNA repair
Females > Males
Name the Disease
Rothmund Thompson

Poikiloderma of face, buttocks, extensor surface
What other findings assoc with Rothmund Thomson?
Dystrophic nails
Juvenile cataracts (age 3-7)
Dental dysplasia
Short with skeletal dysplasias
Hypoplastic/absent radius or thumb
Osteosarcoma, fibrosarcoma, SCC
Neoplasms assoc with Rothmund-Thomson
Osteosarcoma, fibrosarcoma, SCC
Key Disease finding is Hypoplastic/absent radius or thumb?
Defect in Cockayne Syndrome
CSA: ERCC8 gene
CSB: ERCC6 gene --> m/c
Mutated DNA repair mechanism --> UV hypersensitivity & neurodegeneration
Cockayne Syndrome:

Cachectic dwarfs w/ disproportionate long limbs


Scaling erythematous plaques on malar cheeks, neck, hands

Cachectic – subQ fat loss, sunken eyes

Aged appearance

“Mickey Mouse” facies
Microcephaly, large ears
What neurological changes or problems are seen in Cockayne Syndrome? Eye Changes?
Diffuse demyelination
progressive neurologic deterioration --> early death
Intracranial calcification

Retinitis pigmentosa
“salt & pepper” retinal pigment, cataracts, optic atrophy
[also seen in Refsum]

XPB,D, G overlap
Eponym for Trichothiodystrophy
Tay's Syndrome
PIBIDS stands for?
Brittle hair
Intellectual impairment
Decreased fertility
Short Stature
Defect in Tay's Syndrome?
AR, ERCC2, same as XPD mutation
-- DNA repair defect
Sulfur-deficient brittle hair
Short, sparse
Tiger-tail hairs (Trichoschisis)

Of note: Photosensitive patients -- NO actinic damage, NO increased risk of skin cancers!
Other findings in Trichotheodystrophy?
Defect in Hartnup Disease?
SLC6A19 gene

Transporter neutral AA across the apical membrane in the kidney and intestine
Defects = decreased absorption of tryptophan
Tryptophan necessary for nicotinic acid production  patients look like they have “pellagra”
Tx: Nicotinic acid (Niacin) supplement
Name the disease:

Lab abnormalties --
Massive aminoaciduria
Tryptophan in urine
CNS disturbance
Cerebral ataxia
Mild MR
Psychiatric disturbance
Emotional instability
Hartnup Disease

Skin findings:
Photodistributed erythema, scales
Forehead, cheeks, extensor arms, dorsum of hands
Name the three diseases with SLC mutations
Hartnup – SLC6A19

Zinc deficiency – SLC39A4

Citrullinemia type II – SLC25A13

[Type I – Argininosuccinic acid synthetase]
Name the three diseases with RECQL mutations

Werner (2)
Bloom (3)
Rothmund Thomson (4)
Defect in Chronic Granulomatous Disease
Deficient NADPH oxidase enzyme system:
gp91phox – encoded by CYBB gene (XLR) – m/c
p47phox – 2nd m/c; AR
Chronic Granulomatous Disease:
Lymphadenitis (cervical)
Abscesses, Pyoderma, Periorificial dermatitis
Epithelial linings (respiratory, GI)
Hepatic abscesses, osteomyelitis, sepsis
MC infection in Chronic Granulomatous Disease?
Staph aureus m/c bacterial infection
Aspergillus (fumigatus) m/c fungal infection

Bronchopneumonia – most prevalent infection

Female carriers:
No increased infxns
Recurrent stomatitis
Lupus-like lesions on face w/ sun exposure
What diagnostic tests are available to test for Chronic Granulomatous Disease?
Nitroblue tetrazolium (NBT) test – WBC supposed to reduce dye into blue (not in CGD)

Oxidation of dihydrorhodamine to rhodamine w/ flow cytometry – quantitative test
Gene defect in Wiscott Aldrich
XLR, WAS gene
Impaired T-cell activation and NK cell function
Mutation causes problem with signal transduction & actin filament assembly
What is the most common presenting symptom in Wiscott-Aldrich?
Presenting symptom:
1st few months of life --> bleeding problems
Atopic dermatitis, Secondary bacterial infxns, Eczema herpeticum
Thrombocytopenia  bruising, bleeding
Atopic dermatitis, Secondary bacterial infxns, Eczema herpeticum
Thrombocytopenia  bruising, bleeding
Which recurrent infections are common?
Which Ig are low? high?
Impaired immunity — cell-mediated, humoral

Recurrent infections:
Encapsulated bacteria –m/c bacterial infection
HSV, then HPV –m/c viral infection:
- eczema herpeticum

“minute mADE”
Low IgM
High IgA, D, E (ADE)
What Ig are high vs low in Wiscott Aldrich?
minute mADE:
low IgM
high IgA, D, E (ADE)
MC assoc neoplasm in Wiscott Aldrich?
Lymphoreticular malignancy:
Non-Hodgkin’s lymphoma – m/c neoplasm
MC cause of death in Wiskott aldrich?
Infxn > hemorrhage > malignancy – causes of death
Treatment for Wiscott-Aldrich?
BM transplant
Splenectomy w/ abx prophylaxis
Eponym for Hyper IgE syndrome
Job Syndrome or Buckley Syndrome
Defect in Hyper IgE Syndrome

Basic deficiency:
Impaired regulation of IgE function
Deficient PMN chemotaxis
Name the Disease:
Lab findings:
IgE markedly increased
IgD increased
Peripheral eosinophilia
Hyper IgE Syndrome
Describe clinical findings in Hyper IgE Syndrome
Eczematous dermatitis (flexures, postauricular, hairline)
Excoriated papules on scalp, skin folds
Infections – Staph aureus m/c

URI, respiratory infections
coarse facies w/ broad nasal bridge
osteopenia/fractures, scoliosis
retained primary teeth; lack of secondary teeth

Lab findings:
IgE markedly increased
IgD increased
Peripheral eosinophilia
MC of death in Hyper IgE Syndrome
Persistent lung infxn w/o bacterial prophylaxis—m/c cause of death
Treatment of Hyper IgE Syndrome
Cimetidine – immune modulation
Interferon gamma – improve chemotaxis
gamma globulin – decrease IgE levels
Defect in Severe Combined Immunodeficiency
gamma chain (IL2 receptor) gene – m/c
ADA (adenosine deaminase) gene – 20%
JAK3 (Janus kinase 3 in WBCs) gene – chr19
Zap70 deficiency
RAG1, RAG2 – Omenn’s Syndrome
Name the disease:
Cutaneous infections
GVHD – in utero maternal WBCs, transfusion, BMT
Morbilliform rash,SK like dermatitis, LP-like lesions,scleroderma-like lesions

At risk for different types of infections:
Staph, Strep, Candida
Malabsorption due to chronic viral diarrhea
Pneumonia—bacterial, Pneumocystis carinii
Name the disease:
Absent thymic shadow on CXR
Severe Combined Immunodeficiency:

Death in 1 year without BMT
Gene therapy
Defect in Hereditary Angioedema
AD, C1INH gene
C1 esterase inhibitor deficiency or normal but defective
Name the two forms of Hereditary Angioedema
Type I HAE – 85%
<35% of normal
Type II HAE – 15%
levels normal, but dysfunctional
What are some causes of Acquired C1 esterase inhibitor deficiency?
Acquired C1 esterase inhibitor deficiency
Monoclonal B cell dz (lymphoma)
Autoimmune d/o
Clinical picture of Angioedema & pertinent negatives?
-- Laryngeal edema w/ obstruction
-- 10-30% die of airway compromise
Abdominal pain/vomiting/dysphagia

NO urticaria, pruritus, pitting
Lab findings & Treatment of Hereditary Angioedema?
Lab findings:
C2, C4 – decreased
CH50, C3, C1 – normal

Danazol/Stanazol --> stimulate production of functional C1 est inh
FFP/Epi/antihist/steroids --> flares
Defect in Menkes Syndrome?
XLR, MNK or ATP7A gene
Defective copper transport --> low serum copper
Same gene in XLR Cutis Laxa
XLR (CHAD’Z Lovely Kinky WIFE)
MC hair change seen in Menkes?
Others: trichorrhexis nodosa, monilethrix
Menkes Syndrome:
Scalp w/ short, steel-wool hair
Hair broken off in eyebrows
Eyelashes sparse
What cause of death with Menkes?
Early death (2-3 y/o) from PNEUMONIA
Name the disorder:

Hypopigmented doughy, lax skin
Pudgy face; Upper lip like cupid’s bow

Tortuous arteries in brain
Progressive decline—lethargy, seizures, MR

Frontal bossing
Wormian bones in skull sutures
Metaphyseal widening with spurs on long bones
Menkes Syndrome
Lab findings in Menkes syndrome
Low serum copper and ceruloplasmin
Treatment Menkes Syndrome
Copper histidine – start very early!!!
Pamidronate – prevent fractures
What is:
Occipital Horn Syndrome
Variant of Menkes
Occipital horns (exostosis) @ insertion of trapezius and SCM
Abnl facies, short flat clavicle, elbow deformities
Defect in Bjornstad Syndrome
AR, Chr 2
BCS1L Gene
encodes an ATPases necessary for assembly of complex III in the mitochondria
Name the Syndrome:
Pili torti
+/- alopecia
Scalp involved
NOT eyebrows, eyelashes
Bilateral sensorineural deafness
Bjornstad features + Hypogonadism
Crandall has cranberries for testicles…
Causes of Pili Torti:
Bazex’s follicular atrophoderma
Retinoid use
Anorexia nervosa
AR, argininosuccinate lyase deficiency
2nd m/c urea cycle defect
What are some hair changes seen in Argninosuccinic Aciduria?
Trichorrhexis nodosa (50%)
Increased in occiput
Treatment for Argininosuccinic Aciduria
Limit protein intake w/ arginine supplement

Note: other findings --
Failure to thrive
Vomiting, HSM
CNS—lethargy, coma, severe MR, ataxia
Name this finding:
Small white nodes at irregular intervals.
Hairs fracture easily at nodes
Ends resemble broom stick with bristles ends together
What diseases have:
Menkes (pili torti = m/c)
Isotretinoin (curly hairs)
Trauma – m/c!!!
proximal in blacks
distal in Asians & whites
AD, hHb1 & hHb6
Human basic type II hair keratin genes

Elliptical nodes along shaft --> beaded appearance
Undulating variation in diameter
Breaks on internodes
Name the disease that has the following findings:
Keratosis pilaris –nape of neck, back, arms
Teeth abnormalities
Brittle nails
Trichothiodystrophy (Tay’s, PIBIDS)
Light bands = sulfur deficient
Pili Annulati
Alternating bands (Not tiger tails!)
Light bands = air-filled cavities that scatter light
No assoc abnormalities
Eponym and defect for:
AKA: Pili triangulate et canaliculi, Spun-glass hair
AD, sporadic; gene unknown
Dry, blond, shiny
Scalp only
Eyelashes, eyebrows NOT affected
KEY: NOT fragile (everything else in this section has fragile hair!)
Uncombable Hair Syndrome
AKA: Pili triangulate et canaliculi, Spun-glass hair
AD, sporadic; gene unknown
Treatment for Uncombable Hair Syndrome
Biotin 0.3 mg TID
May improve with age

EM finding?
Canal-like groove along shaft
Triangular shaped
Eponym for Hypohidrotic ED
Anhidrotic ectodermal dysplasia
Christ-Siemens-Touraine Syndrome
Defect in Hypohidrotic ED
Genetic mutations
X-linked—most common
EDAR (receptor)
EDARADD (encodes protein that interacts with the receptor)
All involved in NFKB signaling pathway
Name the disease that has the following defects:
Ectodermal defects --
Hypohidrotic ED
Other findings in Hypohidrotic ED?
Other cutaneous findings:
Skin smooth
Effaced dermatoglyphics due to absence of sweat pores
Eczema—2/3 of pts
Sebaceous hyperplasia
What are some of the systemic findings in Hypohidrotic ED?
Systemic findings:
Asthma & rhinitis
Viscous nasal secretions
Thick cerumen
Bronchopulmonary infections
Hypohidrotic ED
Eponym for Hidrotic ED
aka Clouston's syndrome
Defect in Hidrotic ED
AD, Connexin 30 (GJB6) gene
PPK with transgrediens
Clinical findings in Hidrotic ED or Clouston's syndrome?
AD, Connexin 30 (GJB6) gene
PPK with transgrediens

Dystrophic, Paronychia
Normal hair at birth, becomes sparse and brittle; absent in puberty
Tufted terminal phalanges, Thickened skull
Hidrotic ED
What is EEC Syndrome
Ectrodactyly-Ectodermal dysplasia-Cleft lip/palate syndrome
Inheritance and gene defect in EEC Syndrome?
AD, DNA binding domain of p63 gene
Clinical findings of EEC
Dry, scaly skin; Sparse hair; Dystrophic nails
Ectrodactyly—feet > hands
Cleft palate +/- lip
Chronic OM, Hydronephrosis, Lacrimal duct obstruction
EEC Syndrome
AEC syndrome is aka as?
Ankyloblepharon filiforme adnatum-Ectodermal dysplasia-Cleft palate

Hay-Wells Syndrome
Defect in AEC syndrome
AD, Sterile alpha motif (SAM) of p63 gene
May present as:
Collodion baby
Chronic erosive scalp dermatitis --> scarring alopecia
AEC Syndrome
Defnining clinical feature for...?
AEC syndrome:
Ankyloblepharon adnatum filiforme—75%
Lacrimal duct atresia --> conjunctivitis, blepharitis
Name the four subtypes of Pachyonychia Congenita and assoc genes
4 subtypes:
PC1 = Jadassohn-Lewandowsky
PC2 = Jackson-Lawler
PC3 = Schafter-Branauer
PC4 = Pachyonychia congenita tarda
PC1 = K16, K6a genes
PC2 = K17, K6b genes
Name the Disease:

“Omega nails”
all 20 nails affected (fingers>toes)
Thickened, subungual hyperkeratosis
Pincer nails
Focal symmetrical PPK, bullae
Follicular hyperkeratosis on knees, elbows
Pachyonychia Congenita
Omega Nails:
Pachyonychia congenita
Defining feature:

PC1 = oral leukokeratosis (NOT premalignant)
Defining feature:
Natal teeth
Cutaneous cysts: steatocystoma multiplex, epidermoid cysts, vellus hair cysts
Pachyonychia congenita II
Defining Feature:
PC1 + corneal leukokeratosis
Defining Feature:
late onset disease
hyperpigmentation on flexural areas, buttocks and abdomen
Eponym for Nail-Patella Syndrome
Hereditary osteo-onychodysplasia

Fong’s syndrome
Gene defect in Nail Patella Syndrome
AD, LMX1B gene

In close proximity to Collagen V gene

Collagen V is major part of glomerular BMZ --> see kidney problems
Triangular lunulae --> pathognomonic
Longitudinal fissures (thumb m/c)
Nail Patella syndrome
Nail Patella Syndrome
Nail findings in Nail-Patella syndrome
Triangular lunulae  pathognomonic
Longitudinal fissures (thumb m/c)
Bone findings in Nail Patella syndrome/aka Fong's syndrome
Absent or small patella --> pain, OA

Posterior iliac horns

Radial head subluxation, thick scapulae, scoliosis
Nail-Patella syndrome
Nail Patella syndrome:
Posterior iliac horns
Other findings in this syndrome include:
Glomerulonephritis, renal dysplasia/failure

Lester iris – hyperpigmentation of pupillary margin of iris

Heterochromia irides, cataracts, glaucoma
Nail Patella syndrome / Fong's syndrome
What condition does Nail-Patella syndrome look similar too?
Trisomy 8:
Small nails
Absent patella
Alkaptonuria is aka? Gene Defect?
AKA: “Endogenous Ochronosis"

AR, HGO gene (chr 3)
homogentisic acid oxidase deficiency
accumulation of ochronotic pigment
Common presentation of Alkaptonuria in children?
in adults?
Black cerumen, underwear or diapers, sweat

Dark urine with high pH (>7.0) --> diapers turn black with NaOH
Adults --> “Blue man group”
Facial blue-gray pigmentation

Blue-gray pigmented cartilage & tendons (nose, ears, hands)
Blue-gray sclera
Assoc findings?
Severe arthropathy of large joints
Intervertebral disk calcification
Mitral/aortic valvulitis --> increased risk of MI
Banana body in Dermis:
Eponym and defect in Fabry Disease
AKA: Angiokeratoma corporis diffusum
XLR, -galactosidase-A (GLA) gene
Glycosphingolipids accumulation in vascular endothelium --> heart, brain, kidneys
XLR (CHADZ Lovely Kinky WIFE)
What is the disease:
Acroparesthesias & paroxysmal acral painful crises with edema (kids dip their hands in toilet)
Diphenylhydantoin, carbamazepine
Acromegaly features
Fabry Disease
Name the disease:
Maltese crosses in urine (birefringent lipid globules)
Fabry Disease
What causes premature death in Fabry's disease?
Deposition leads to various problems:

Premature death due to:
CVA, peripheral neuropathy
MI/cardiac problems
Progressive renal failure
EYE—Cornea verticillata (whorled-like opacities) & torturous retinal vessels

see in Fabry's Disease
Name the syndromes assoc with Angiokeratomas

Fucosidosis (alpha-L-fucosidase deficiency)

Sialidosis (defect: NEU1 gene)

Beta-mannosidase deficiency


GM1 gangliosidosis

Kanzaki’s disease (alpha-N-acetylgalactosaminidase deficiency)
What should you think of in a patient with acral paresthesias with no cutaneous findings and other systemic problems similar to Fabry’s?
Defect in Gaucher disease
AR, Acid-ß-Glucocerebrosidase (GBA) gene
-- glucocerebroside accumulates in histiocytes in all types of organs
Name the three types of Gaucher disease
3 Types:

Type I – adults; more common; Ashkenazi
Type II – infantile
Type III – juvenile
Erlenmyer flask deformity -- seen in Gaucher Disease, Type I

Type I—Adult form
Hyperpigmentation of faces, neck & hands (bronze)
Hepatomegaly with hypersplenism --> Petechiae, ecchymosis
Enlarged lymph nodes
Bone problems:
- Pain
- Fractures
- Erlenmeyer flask deformity
aseptic necrosis of femoral head
- vertebral collapse
Pingueculae -- seen in type I adult form of Gaucher disease
Name the disease:
CNS deterioration
Hypertonic, rigid/spastic, catatonic
Difficulty swallowing
In adult form – there’s some neuronal glucocerebrosidase activity
Aspiration pneumonia – death by age 1-2
Type II, infantile form of Gaucher disease
Cause of death in Type II, infantile form of Gaucher Disease
Aspiration pneumonia
How are type II and type III Gaucher disease different?
Type III Dz is the juvenile form and has the findings of type II PLUS bony involvement
Gaucher Disease:
BM biopsy --> Gaucher’s cells (histiocytes filled with glucocerebroside )
Treatment of Gaucher Disease
Enzyme replacement
- Type I only
- Does not cross BBB, not useful in types II & III
- BM transplantation

Supportive for II & III
Name the main differences in the three types of Gaucher Disease
Defect in Niemann-Pick Disease
AR, Sphingomyelin phosphodiesterase-1 (SMPD-1) gene
sphingomyelin accumulation in foam cells w/in all organs
Name the different types of Niemann-Pick disease
Three types
Type A – infancy, m/c; Ashkenazi Jews
Type B – infancy to childhood
Type C – childhood; French-Canadians
Name the Disease:
Xanthomas, JXG
Cherry red spots in eyes
Enlarged lymph nodes
Pychomotor degeneration
Failure to thrive/emaciated
Bronchopneumonia – m/c cause of death by age 2-3
Niemann-Pick Disease: type A
Describe type B and type C Niemann Pick Disease
Type A features minus CNS problems
Have higher residual level of enzyme
Totally different gene – NPC gene
DEFECT: cholesterol esterification, normal sphingomyelinase
Developmental delay
Progressive psychomotor deterioration
Niemann-Pick cell: “foamy blue histiocytes” with mulberry appearance
Differential Dx?

Name the Mucopolysaccharidoses and their defect
Name the disease:

COMMON FINDINGS—Short, thick & hairy
Name the Mucopolysaccharidoses that does not have corneal clouding?
Hunter’s, Sanfilippo’s
What are the common findings in mucopolysaccharidosis?
COMMON FINDINGS—Short, thick & hairy
Short (except Scheie), broad hands & short fingers, hernias, spinal derformity, short neck, joint laxity
Corneal clouding (except Hunter’s, Sanfilippo’s)
Heart problems
Bronchopneumonia—often end stage; sleep apnea with thickened narrow airway
What is the only XLinked Mucopolysacharridoses?
Hunter Syndrome

XLR – it’s the only one!
Iduronate sulfatase deficiency
Characteristic skin finding—Pebbling between angles of scapulae & posterior axillary line
CNS = big problem
Which of the mucopolysaccharisdoses has occipito-atlantic instability?
Hurler’s & Morquio’s
Occipito-atlantic instability --> quadraplegic
Cause of death in patients with mucopolysaccharidoses?
Early death within 2nd decade (cardio-pulmonary decompensation)
EXCEPT: Scheie—normal lifespan
Name the Disease:
Retention hyperkeratosis with normal epidermal proliferation
Fine white scale, spares flexures & face
Hyperlinear palms
Atopic dermatitis in 50%
Keratosis pilaris
Ichthyosis Vulgaris
Inheritance and Defect in Ichthyosis Vulgaris?
Inheritance & gene defect?
AD with defect in profilaggrin synthesis
What is the histo finding in Ichthyosis Vulgaris?
absent granular layer (best bx site is anterior shins)
Name the disease:

Brown scales on neck & extensors, relative sparing of flexures, palms, face
Eye finding?
Comma-shaped corneal opacities (asymptomatic)
X-linked Ichthyosis
X-linked Ichthyosis: Inheritance/gene defect?
XLR with arylsulfatase-c gene defect
Name the disease:
Cryptorchidism- 20%
Increased risk of testicular cancer & ALL
Failure of labor: decreased placental sulfatase
X-linked Ichthyosis
Name two syndromes that may result from contiguous gene deletions of the XLR arylsulfatase-c gene (XL Ichthyosis):
Kallman Syndrome
X-linked recessive chrondrodysplasia punctata (arylsulfatase E gene defective)
Defect in Kallman syndrome?
XLR with defect in KAL1 (encodes anosmin)
Name the Disease:
Hypogonadism and cryptorchidism
Mild feminization
Renal agenesis
Kallmann Syndrome

XLR with defect in KAL1 (encodes anosmin)
Epidermolytic Hyperkeratosis is aka?
Bullous CIE
Defect in Bullous CIE?
AD with defect in keratins 1 & 10
(aka Epidermolytic Hyperkeratosis)
How does a newborn present with Epidermolytic hyperkeratosis?
Newborn: widespread bulla and erythroderma, sepsis, H2O loss
How does an infant-adult with epidermolytic hyperkeratosis look like?
Infant-adulthood: generalized “corrugated” hyperkeratosis (dark warty scales with spiny ridges increased in flexural areas)

+/- palmoplantar keratoderma
Malodorous, macerated intertriginous areas
Post-puberty may localize to flexural areas
Name the disease:
dark warty scales with spiny ridges increased in flexural areas

+/- palmoplantar keratoderma

Malodorous, macerated intertriginous areas

Post-puberty may localize to flexural areas
Epidermolytic Hyperkeratosis
EM finding in EHK?
EM: clumped keratin filaments
What medication should you avoid in EHK?
Generally avoid systemic retinoids; some advocate short courses of systemic retinoids for adult flares
Avoid keratolytics --> denuded raw skin
Parents with epidermal nevi with EHK features may have children with what?
Parents with Epidermal Nevi that have EHK features may pass on classic disease to their children due to gonadal mosaicism (“they” love to ask this on tests)
Ichthyosis Bullosa of Siemens
Inheritance/gene defect?
AD defect in keratin 2e
Name the Disease:
Highly penetrant and evident from birth
Fragile blisters early in life
Later with hyperkeratotic plaques on the elbows and knees
Rippled hyperpigmentation in flexural areas
Superficial molting or peeling of the skin: 'Mauserung' phenomenon
Ichthyosis Bullosa of Siemens
Gene Defect in Diffuse PPK (Unna-Thost/Vorner)
AD with defects in K9 and K1 (Vorner is K9>K1 and Unna-Thost is K1)
Gene Defect in Howel-Evans Syndrome
AD with defect in the TOC locus distal to K1 (envoplakin is not the defective gene within the TOC locus)---Tylosis & Oesophageal Cancer
Clinical presentation of Howel-Evans Syndrome
2nd decade: PPK, NO transgrediens
After 3rd decade: esophageal carcinoma
Oral leukoplakia in one kindred
Name the disease:
Starfish-shaped or linear keratoses on dorsal hands, feet, elbows, knees
Scarring alopecia, HF hearing loss
Retinoids may prevent auto-amputation
Vohwinkel Syndrome
Defect in Vohwinkel Syndrome
AD with defect in GJB2 (connexin-26 classic form with deafness- same gene as KID) or loricrin (#1 component of cornified cell envelope)

Connexin-26 --> deafness
Loricrin variant--> ichthyosis
Defect in Mal de Meleda
AR with defect in SLURP-1 (proteins important in cell signaling and adhesion)
Name the disease:

Glove-stocking PPK WITH transgrediens
Fissures, malodorous, pseudoainhum at DIP, hyperhidrosis
Koilonychia and subungual hyperkeratosis
Hyperkeratotic plaques on elbows/knees
Mal de Meleda:

AR with defect in SLURP-1 (proteins important in cell signaling and adhesion)

Island of Meleda in the Adriatic sea off Bosnia
Defect in Mal de Meleda
AR with defect in SLURP-1 (proteins important in cell signaling and adhesion)
Name the disease:

Glove-stocking PPK WITH transgrediens
Fissures, malodorous, pseudoainhum at DIP, hyperhidrosis
Koilonychia and subungual hyperkeratosis
Hyperkeratotic plaques on elbows/knees
Mal de Meleda:

AR with defect in SLURP-1 (proteins important in cell signaling and adhesion)

Island of Meleda in the Adriatic sea off Bosnia
Defect in Mal de Meleda
AR with defect in SLURP-1 (proteins important in cell signaling and adhesion)
Name the disease:

Glove-stocking PPK WITH transgrediens
Fissures, malodorous, pseudoainhum at DIP, hyperhidrosis
Koilonychia and subungual hyperkeratosis
Hyperkeratotic plaques on elbows/knees
Mal de Meleda:

AR with defect in SLURP-1 (proteins important in cell signaling and adhesion)

Island of Meleda in the Adriatic sea off Bosnia
Defect in Ichthyosis Vulgaris
FLG gene
Defect in Profillagrin synthesis
Defect in X-linked Ichthyosis
STS gene defect
(arylsulfatase-c gene)

Increased levels of cholesterol sulfate leads to decreased cholesterol and retention keratosis
What two syndromes may result from continguous gene deletions in X-linked Ichthyosis?
Kallman Syndrome
X-linked recessive chondrodysplasia punctata (arylsulfatase E gene defective)
Defect in Kallman Syndrome
XLR -- defect in KAL1 (encodes anosmin)
hypogonadism and cryptoorchidism

mild feminization


Kallman Syndrome
Epidermolytic Hyperkeratosis is aka? Defect?
Bullous CIE

Defect in Keratins 1 and 10
Clinical Presentations:
Newborn -- widespread bulla and erythroderma
Infant/Adult -- generalized hyperkeratosis

maloderous, macerated intertriginous areas

EM: clumped keratin filaments
Epidermolytic Hyperkeratosis
Patients with epidermal nevi that have EHK features may pass on what to their children?
Classic Epideromolytic Hyperkeratosis
May manifest as shedding in layers "Mauserung" (molting)
Ichthyosis Bullosa of Siemens
Defect in Ichthyosis Bullosa of Siemens?
AD defect in keratin 2e

Clinical: fragile blisters early in life, followed by hyperkeratotic plaques on the elbows and knees -- rippled hyperpigmentation in flexural areas
Defect in Lamellar Ichthyosis
AR w/ TGM1 (keratinocyte transglutaminase gene defect)
Collodion Baby
Plate-like scales
Scarring alopecia
Lamellar Ichthyosis
Another name for Congenital Ichthyosiform Erythroderma (CIE)
Non-Bullous CIE
Defect in Non-Bullous CIE (Congenital Ichthyosiform Eryhtroderma)
defects in TGM1 and Lipogenases: ALOX12B & ALOXE3
Collodion Baby
Erythroderma, fine white scale, flexures involved, plate-like scales on legs
+/- PPK
Cicatricial alopecia
Congenital Ichthyosiform Erythroderma
Defect in Harlequin Fetus
Suspected problem with profillagrin to fillagrin (candidate gene is ABCA12)
What do you see on EM with harlequin fetus?
absence of lamellar bodies (massive hyperkeratotic plates)
Infancy: Ichthyosiform erythroderma & plates
Later: plate-like scales with no erythema and emphasized in flexures; pruritus
MR, spastic di/paraplegia, scissor gait, speech difficulties
“Glistening dot” retinal degeneration
Sjogren-Larsson Syndrome

AR with defect in fatty aldehyde oxidoreductase (FALDH) gene (epidermal lipid synthesis); (ALDH3A2)
increased phytanic acid - replaces NL fatty acids in skin and organs

Mild ichthyosis (skin not impressive)

Ataxia, neuropathy
Retinitis pigmentosa (salt & pepper) and sensironeural deafness

Arrhythmias w/ heart block, CHF
Refsum Syndrome

AR with defect in phytanoyl-CoA hydroxylase genes PAHX and PEX7
Name the key findings in Buschke-Ollendorf
AD dominant
dermal plaques/papules
Osteopoikilosis on Xray
Focal sclerotic densities in long bones, pelvis, and hands
Name the Dz:
AD dominant
dermal plaques/papules
Osteopoikilosis on Xray
Focal sclerotic densities in long bones, pelvis, and hands
Name the Dz:
Numberous symmetric asymptomatic dermal nodules on back
usu in mid to late teens
Assoc with MEN type I
may also see angiofibromas, cafe-au-lait macules and lipomas
Familial cutaneous collagenomas
Describe familial cutaneous collagenomas
Name the Dz:
Numberous symmetric asymptomatic dermal nodules on back
usu in mid to late teens
Assoc with MEN type I
may also see angiofibromas, cafe-au-lait macules and lipomas
What are some associated skin findings with tuberous sclerosis?
Adenoma sebaceum
Periungual fibromas
Ash-leaf macules
Eruptive collagenomas has been associated with what dz?
Gene defect in Non-bullous CIE aka "congenital ichthyosiform erythroderma"?
TGM1 defect

Presents as collodion baby in 90% of cases
Gene defect in Bullous CIE (aka "epidermolytic hyperkeratosis")
K1 and K10
Presents as generalized erythema with superimposed superficial blisters and erosions
Omenn syndrome defect
RAG1 and RAG2
AR form of severe combined immunodeficiency
Exfoliative erythroderma with diffuse alopecia
Inheritance? Gene Defect for Ataxia-Telangiectasia?
ATM (ataxia-telangiectasia mutated) gene
AR inheritance
Normal function of the ATM gene, mutation causes what?
Ataxia-Telangiectasia Mutated gene:
Codes for Phosphotidylinositol 3-kinase-like protein: senses early damage to DNA, initiates apoptotic and cell cycle responses that allow DNA repair

Mutation: Progressive neurologic deterioration -- defective DNA repair in nerve cells, leads to progressive depletion of Purkinje cells in the cerebellum (fails to cease DNA synthesis after UV radiation)
MC cause of death in Ataxia Telangiectasia?
Bronchiectasis with respiratory failure
Lab findings in Ataxia-Telangiectasia?
Almost all have:
Elevated Alpha-Fetoprotein & CEA

Decreased or absent:
IgA2, IgG2 and IgG4, IgE

Abnormally developed or absent thymus

14:14 seem to predict the development of lymphoma
(female heterozygotes: also have a risk of breast CA)
What is APECED? Gene defect?
APECED = Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome

AIRE gene defect: AutoImmune REgulator
-- encodes DNA transcription factor
Familial dysautonomia eponym?
What group is seen to Riley-Day?
Ashkenazi Jews
Gene for Riley-Day? Describe the Syndrome?
IKBKAP (I Kan't Be KAPped)
Hallmark is insensitivity to pain
Episodic hyperhidrosis
Blotchy erythema of the face and trunk
Deficient lacrimation
Absense of fungiform papillai on the tongue
Failure to thrive
Mental retardation
Ichthyosis Vulgaris
X-linked Ichthyosis (aka?)
Steroid sulfatase deficiency; Gene Xp22.32, X-linked recessive
Epidermolytic Hyperkeratosis
aka Bullous congenital ichthyosiform erythroderma
aka Bullous ichthyosis
50% spontaneous mutation;
keratin K1, K10 genes on Chromosome 12q, 17q respect
Lamellar Ichthyosis
AR; transglutaminase 1 (TGM1) gene on 14q11
Congenital Ichthyosiform Erythroderma (CIE)
aka Nonbullous CIE
Harlequin Fetus
AR most likely, genetic heterogeneity with recent description of de novo deletion of 18q21
Sjogren-Larsson Syndrome
AR; Fatty aldehyde dehydrogenase (FALDH) gene 17p11.2
Refsum Syndrome
aka Phytanic acid storage disease; Heredopathia atactica polyneuritiformis;
AR; PAHX gene on 10p and PEX7gene on 6q
Conradi-Hunermann Syndrome
aka X-linked dominant chondrodysplasia puntata;
aka Conradi-Hunermann-Happle syndrome
CHILD syndrome
Congential Hemidysplasia with Ichthyosiform erythroderma and Limb Defects (CHILD); aka Unilateral congenital ichthyosiform erythroderma
Netherton Syndrome
aka Ichthyosis linearis circumflexa (ILC);
AR; SPINK5 gene on 5q32
Erythrokeratoderma Variabilis
aka Mendes da Costa syndrome;
AD; GJB3 gene on 1p35
KID Syndrome
Keratitis-Ichthyosis-Deafness syndrome;
AD and recessive transmission reported;
GJB2 gene on 13q11-12
Diffuse Palmoplantar Keratoderma (PPK)
aka Vorner PPK or Epidermolytic PPK, Keratin genes 9 and 1 (on chromosome 17 and 12);
aka Unna-Thost PPK or Nonepidermolytic PPK (keratin 1 gene);
AD transmission
Howell-Evans Syndrome
AD; tylosis and esophageal cancer (TOC) gene locus on 17q25
Vohwinkel Syndrome
aka PPK mutilans;
aka Keratoderma herditaria mutilans;
AD: classic form with deafness: GJB2 gene on 13q11-12
Loricrin-variant: loricrin gene on the epidermal differentiation complex (EDC) on 1q21
Mal de Meleda
aka Keratoderma palmplantaris transgrediens;
AR; secreted Ly-6/uPar related protein 1 (SLURP1)gene on 8qter
Papillon-Lefevre Syndrome
aka palmoplantar keratoderma with periodontosis; AR, CTSC gene on 11q14
Richner-Hanhart Syndrome
aka Tyrosinemia type II;
AR; tyrosine aminotransferase gene on 16q22.1-q22
Darier Disease
aka Darier-White Disease;
aka Keratosis follicularis;
AD, ATP2A2 gene on 12q23-24
Epidermal Nevus Syndrome
aka Ichthyosis hystrix;
aka Inflammatory Linear Verrucous Epidermal Nevus (ILVEN);
Linear sebaceous nevus syndrome;
sporadic inheritance
Oculocutaneous Albinism Type 1 (OCA1)
aka Tyrosinase-negative albinism;
AR, tyrosinase (TYR) gene on 11q14-q21
Buschke Ollendorf
LEMD3 or MAN1 gene
1. Dermatofibrosis lenticularis disseminata
2. Osteopoikilosis
Normal lifespan
McCune-Albright Syndrome
Post-zygotic somatic mutations activating the GNAS1 gene on Chr 20
"Coast of Maine" Cafe au Lait
Polyostotic fibrous dysplasia
Hyperthyroidism and Precocious puberty
Focal Dermal Hypoplasia eponym
Goltz syndrome
X-linked dominant
Soft red-yellow nodules (fat herniations) in Blaschko's lines
Menkes findings?
Xlinked recessive
MKN or ATP7A gene
Pili torti, doughy skin, MR, metaphyseal widening with spurs in long bones
Synonym for Alkaptonuria
Endogenous Ochronosis
Causes of exogenous achronosis?
Antimalarials, hydroquinone
Alkaptonuria Inheritance & Gene?
HGO Gene:
Homogentisic acid oxidase deficiency
Results: accumulation of homgentisic acid in tissue

Chr 3q21-q23
Key findings in Alkaptonuria
Blue-gray pigmentation on nose, cheeks, forehead, axillae; pigmented cartilage and tendons; pigmented sweat/cerumen; arthropathy; dark urine with pH above 7.0 -- discolors diapers after cleansing with alkaline soaps; mitral and aortic valvulitis (RISK OF MI INCREASED)
dark urine / discolored diapers
blue-gray pigmentation
Eponym for Fabry Disease
Angiokeratoma corporis diffusum
Anderson-Fabry Disease
Enzyme Defect in Fabry Dz
X-linked Recessive
alpha-galactosidase A (GLA) gene
Chr Xq21.33-q22

Accumulation of neutral glycosphingolipids (ceramid trihexoside) which accumulate in vascular endothelium
Incidence of Fabry and Dx?
1:40,000 males; heterozygote females have variable expression and c/b symptomatic.

Can dx with CVS sampling
Enzyme assays
Skin or BM Bx
Urine Sediment
Key features of Fabry's
The "A's"

Acroparesthesias & paroxysmal acral painful crises with edema (kids dipping hands in toilet)
Anhidrosis - hypohidrosis
Acromegaly features
Angina: Acute MI, mitral insufficiency

others: Kidney deterioration with "Maltese Cross" birefringent lipid globules;
CVA, corneal opacities
Tx of Fabry's
Enzyme replacement
Inheritance of Gaucher Dz, gene defect?
Acid-beta-glucocidase (ABG) gene
Chr 1q21

Decreased glucocerebrosidase activity resulting in accumulation of glucocerebroside in histiocytes (Gaucher's cells)
How many types of Gaucher's Dz?
Two types:

Type I (adult) - usu in later adulthood; ASHKENAZI Jews, NO CNS symptoms

CNS Symptoms seen in:
Type II (infantile) -- 2 to 3 months of life
Type III -- rare, rapid deterioration like type II
Key Features of Gaucher Dz
Type I
diffuse hyperpigmentation (bronze face)
bone pain/fractures/fragile bones(erlenmyer flask deformity, aseptic necrosis of femoral head)
hepatomegaly, hypersplenism

Type II
CNS deterioration,
hypertonicity and neck rigidity, laryngeal spasm
chronic aspiration - aspiration PNA, death by age 1-2

Type III -- hepatosplenomegaly, bone and slow neurodegeneration (basically type II with bone involvement)
Lipid-engorged macrophage with "crumpled tissue paper" appearance
Gaucher cells
Gene defect in Niemann-Pick Disease
sphingomyelin phosphodiesterase-1 SMPD-1

MN: "No Man Picks" his nose with his "Sphing"er
accumulation of sphingomyelin in histiocytes w/in all organs
Cherry red spots are found in what dzs?
Niemann-Pick (SMPD-1)
Generalized sialidosis
Sandhoff's disease
Name the mucopolysaccharidoses and their inheritance
Hurler, Scheie syndrome: 4
Hunter's syndrome: X
Sanfilippo syndrome: several gene loci reported
Morquio's (A): 16
Maroteaux-Lamy syndrome: 5

ALL autosomal recessive, EXCEPT Hunter's (X-linked)

ALL have short stature, except Sanfilippo's.

Common findings: Short, Thick & Hairy. Bone problems: short stature, dysostosis multiplex, broad hands with short fingers
Name the Mucopolysaccharidoses and the gene defect
Hurler's, Scheie: alpha-L-iduronidase; dermatan, heparan sulfate

Hunter's: iduronate sulfatase; dermatan, heparan sulfate (cobblestone back)

Sanfilippo's: (A)heparan-N-sulfatase, (B) alpha-N acetylglucosaminidase, (C) acetyl-CoA: alpha-glucosaminide acetyltransferase, (D) N-acetylglucosamine 6-sulfatase; heparan sulfate

Morquio's: (A) hexosamine 6-sulfatase (B) beta-galactosidase; keratan sulfate

Maroteaux-Lamy: arylsulfatase B; dermatan sulfate
Gene defect in:
Hurler's, Scheie
alpha-L-iduronidase; dermatan, heparan sulfate
Gene defect in:
iduronate sulfatase; dermatan, heparan sulfate (cobblestone back)

Gene defect in:

(A)heparan-N-sulfatase, (B) alpha-N acetylglucosaminidase, (C) acetyl-CoA: alpha-glucosaminide acetyltransferase, (D) N-acetylglucosamine 6-sulfatase; heparan sulfate

Gene defect in:
(A) hexosamine 6-sulfatase (B) beta-galactosidase; keratan sulfate
Gene defect in:
arylsulfatase B; dermatan sulfate
Forms of Multiple Carboxylase Deficiency
Two forms: both AR

Holocarboxylase synthetase deficiency: HLCS gene, presents during 1st few days to months of life

Biotinidase deficiency (BTD gene) - presents later in life
Gene defect for multiple carboxylase deficiency
Holocarboxylase synthase deficiency: holocarboxylase synthetase (HLCS) gene
[Hypotonia, vomiting]

Biotinidase deficiency: biotinidase (BTD) gene
[optic atrophy, high-frequency hearing loss]

Both have decreased biotin in serum -- leads to metabolic acidosis; hyper-ammonemia;
Urine has organic aciduria -- 3-hydroxy-isovaleric acid
Gene defect in Phenylketonuria
Phenylalanine hydroxylase deficiency - accumulatiion of phenylalanine that competitively inhibits tyrosinase (hypopigmentation and toxic CNS effects)

Phenylalanine hydroxylase (PAH) gene

Chr locus 12q24.1

think, "white mouse w/ eczema and scleroderma" (mousy urine, albinism, eczema, sclerodermoid changes)
Eponym for hepatolenticular degeneration
Wilson's Disease
Gene defect in Wilson's Dz?
ATB7B gene on Chr 13
(vs ATB7A in Menkes)
encodes: adenosine triphosphatase CU2+ transporting polypeptide results in defect in biliary excretion of copper/copper transport
Eye findings in Wilson's Dz?
Kaiser-Fleisher rings (copper deposits in Descemet's membrane)
Gene defect in acrodermatitis enteropathica
SLC394A on Chr 8

gene encodes intestinal zinc-specific transporter protein, results in defective zinc absorption from the gut (also has low alk phos levels)
Gene defect in hemochromatosis
HFE gene

hemochromotosis-HFE gene locus 6p21.3

increased intestinal iron absoroption and organ deposition
What is the clinical triad of hemochromatosis?
Skin hyperpigmentation
Diabetes (aka 'bronze diabetes')
Gene defect in homocystinuria
Cystathionine B-synthase (CBS) gene
Chr 21q22.3

Mutation leads to cystathionine beta-synthase deficiency which accumulates homocystine; leads to abnormal crosslinking of collagen
Clinical features of homocystinuria
The "M's":
Malar rash
Marphanoid body
Mental Retardation
Methionin levels elevated
Musculoskeletal problems
Myopia (Downward lens displacement vs upwartd lens displacement in Marfans)
Gene inheritance of the hyperlipoproteinemia
Type I: AR

Type II: AD

Type III: AR

Type IV: AD
Type V: AD
Palmar Xanthomas are seen in which hyperlipoproteinemias?
CAD and CVAs are seen in which hyperlipoproteinemias?
(II die from premature atherosclerosis!)
Pancreatitis is seen in which hyperlipoproteinemias?
I, V
DM is seen in which hyperlipoproteinemias?
HSM is seen in which hyperlipoproteinemias?
I, V
Dz's associated with angiokeratomas

β-Galactosidase deficiency

Fucosidosis (α-L-fucosidase deficiency)

Sialidosis (defect: NEU1 gene)

β-mannosidase deficiency


GM1 gangliosidosis

Kanzaki’s disease (alpha-N-acetylgalactosaminidase deficiency)
What is Cornea Verticillata?
Whorled-like opacities and tortuous retinal vessels seen in FABRY's
Describe the four types of Neimann-pick Dz?
Type A – infancy, M/C type; Ashkenazi Jews, CNS Sx

Type B – infancy to childhood, NO CNS Sx (Type A without CNS involvement)

Type C – childhood; French-Canadians, CNS Sx (Different Gene -- NPC gene; defect in cholesterol esterification, normal sphingomyelinase)

Type D – As per Andrews

Type C&D: assoc cholesterol metabolism defects
Diagnosis of PKU
Serum: elevated phenyl-alanine
Urine: elevated phenyl-pyruvic acid (add ferric acid, urine becomes a deep green)
Wilson's Disease clinical findings


Basal ganglia degeneration
Blue (Azure) lunulae

Copper ↑
Ceruloplasmin ↓
Cirrhosis -- Liver CA
Corneal deposits (Kayser-Fleischer ring)
Choreiform movements

Gene defect in Citrullinemia
(vs SLC39A4 in Acrodermatitis Enteropathica)
Name the different types of Citrullinemia
2 Types:
Type I – Argininosuccinic acid synthetase deficiency
(inborn error of urea synthesis)
Citrulline & aspartic acid conversion to argininosuccinic acid is defective
-- Keratin is 16% arginine --

Hair: pili torti, Trichorrhexis Nodosa, atrophic hair bulbs
Skin: defect leads to acrodermatitis enteropathica like dermatitis

Type II – SLC25A13 (adult onset), affects only liver
-- Exclusively seen in adult Japanese
This is seen in what disorders?
Trichorrhexis Nodosa:
1. Genetic AD Form, normal hair at birth, then develops TN in months, no assoc problems

2. Arginosuccinic aciduria
3. Menkes syndrome
4. Citrullinemia
Describe the characteristic skin findings in hyperlipoproteinemias and which type they are found in.
Eruptive xanthomas – I, III, IV
Xanthelasma – II,III
Xanthoma striata palmaris – III
Tendinous xanthoma – II
Tuberous xanthomas at pressure points – II, III
Planar xanthoma – II
Eponym for Juvenile Gout?
Lesch-Nyhan syndrome
Defect in Lesch-Nyhan syndrome?
Hypoxanthine-Guanin-Phosphoribosyltransferase (HGPRT) deficiency

enzyme deficiency in purine metabolism
Clinical findings in Lesch Nyan syndrome
Gout Sx
Orange Cyrstals in Diapers

Self-mutilating behavior (head-banging, biting lips, and fingers)

Kidney stones (uric acid)

Severe CNS sx: progressive MR, choreoathetosis

Tx: allopurinol
Birth: erythroderma, dehydration

Infancy: Ichthyosis linearis circumflexa, atopic dermatitis, hypernatremia
Trichorrhexis invaginata
-- pili torti or trichorrhexis nodosa are also possible

Anaphylactic food reactions with elevated IgE

Greatly increased percutaneous absorption

May improve at puberty
Netherton Syndrome
Defect in Netherton Syndrome
AR w/ defect in SPINK-5

Serine-Protease inhibitor LEKT1 gene
Defect in Cornelia de Lange Syndrome
NIPBL mutation
Describe Cornelia de Lange
hypertrichosis: forehead, lateral face, shoulders, back, low anterior hairline, synophrys, trichomegaly.
Distinctive facies, upper extremity anomalies, microencephaly, MR, "growling cry"
Describe Rubinstein-Taybi syndrome
Hypertrichosis: lateral face, shoulders, back, thick eyebrowns, trichomegaly
Midfacial vascular stains, kelods, pilomatricomas
Broad thumbs/halluces, beaked nose, high arched palate, short stature, MR
Defect in Rubinstein-Taybe syndrome
CREBBP mutations
Cornelia de Lange syndrome
Rubenstein-Taybi syndrome
Eponym for POEMS syndrome?
What does POEMS stand for?
Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes
[a rare multisystemic disease in the setting of a plasma cell dyscrasia)
Describe Setleis syndrome
AR, defect?
Bitemporal scar-like depressions
Leonine facies
Abnormalities of eyelashes, eyebrows and eyelids
Flattening of nasal bridge
Pursed lips
Normal growth and development
Puerto Rican ancestry
Describe Lymphedema Distichiasis syndrome -- defect and clinical picture
AD, defect?
Variable penetrance
Other disorder with FOXC2 defect?
Meige syndrome
(Late onset congenital lymphedema)
Another name for Nail-Patella syndrome
Hereditary Osteo-Onychodysplasia (HOOD)
Gene defect for Nail-Patella Syndrome
AD inherited condition; assoc with mutations in the LMX1B gene (transcription factor that regulates collagen synthesis)
Name the two types of Pachyonychia Congenita
Type I = KRT6a and KRT16 defect, assoc with oral leukokeratosis
Type II = KRT6b and KRT 17 defect, assoc with premature dentition and pilosebaceous cysts
another name for Darier dz and what nail finding
aka Follicular Dyskeratosis

red and white longitudinal streaks, V-shaped indentation of distal margin
Types of Acanthosis Nigricans
Type I: assoc w/ malignancy;
Type II: familial
Type III: asoc w/ Obesity & Endocrine (insulin resistance)
Two Endocrine Syndromes with AN
Type A syndrome:
HAIR-AN syndrome -- characterized by hyperandrogenemia(HA), extreme insulin resistance (IR) and acanthosis nigricans (AN).
Distinguished from type B from lack of antibodies to insulin receptor or other evidence of autoimmune disease. In Young Black Women.
Type B - in older women w/ signs of autoimmune disease (circulating Ab to the insulin receptor). Pts w/ uncontrolled DM, acanthosis nigricans and ovarian hyperandrogenism
Types of Primary Dyslipidemia
I - Chylomicrons (eruptive)
IIa - LDL (tendon&tuberous)
IIb - VLDL & LDL (tendon&tuberous)
III - IDL (palmar xanthomas)
IV - VLDL (eruptive)
V - Chylomicrons & VLDL (eruptive)
Vogt Triad
epilepsy, angiofibromas (adenoma sebaceum), and mental retardation associated with tuberous sclerosis; affects 25% of patients