Bafl Exam 3: Ichthyoses And Erythrokeratodermas

Front 1

What are the X linked recessive disorders?

Back 1

X-Linked Recessive Diseases
CHAD's KINKY WIFE

Chronic granulomatous disease
Hunter's syndrome
Anhidrotic ectodermal dysplasia
Dyskeratosis congenita
Menke's Kinky hair syndrome
Wiskott-Aldrich syndrome
Fabry's disease
Ehlers-Danlos syndrome, Type V and IX

Front 2

What are the X linked dominant disorders?

Back 2

X-Linked Dominant Diseases
GO IN a CHILDS HAPPY FACE

Goltz syndrome (focal dermal hypoplasia)
Incontinentia pigmenti
Child syndrome
Happle form of Punctate Chondrodysplasia
Oral-facial-digital syndrome

or CCFIB

CHILD

Conradi Hunermann Happle

Focal Dermal Hypoplasia

IP

Bazex

Front 3

The two common ichthyosis are:

Ichthyosis Vulgaris

and

X linked Recessive Ichthyosis

What are the gene defects? How do their clinical presentations differ?

Back 3

Ichthyosis Vulgaris- autosomal semidominant defet in filaggrin (remember, profilaggrin is a main component of the keratohyaline granules, produces NMF, this is also defect in atopic dermatitis)

Presents as fine, white, flakey scales on extensor extremities, usually in children, improves with age (shin is the best place for biopsy)

X linked Recessive Ichthyosis- Steroid sulfatase deficiency (STS gene), increased production of choleterol 3, which inhibits transglutaminase 1

Clinically presents during neonatal period as generalized polygonal, white to dark brown scales (dirty necks)

Front 4

What lab findings are associated with X linked recessive ichthyosis?

Back 4

X linked recessive ichthyosis (steroid sulfatase deficiency)

see increased betal fraction LDL on lipoprotein electrophoresis

increased plasma cholesterol sulfate

decreased steroid sulfatase activity

remember, steroid sulfatase is deficient --> increase cholesterol 3 sulfate --> inhibits transglutaminase 1

Front 5

What is Kallman syndrome?

Back 5

defect in KAL1

hypogonadism, cryptochidism, micropenis, anosmia, renal agenesis

no peen, can't smell, boo.

Front 6

What is X linked recessive chondrodysplasia punctata?

Back 6

Defect in golgi enzyme arylsulfatase E (ARSE gene)

see chondrodylsplasia punctata, brachytelephalangy (short fingers), nasomaxillary hypoplasia)

NTBCW XLdominant chondrodysplasia punctata (Conradi-Hunermann-Happle)

Front 7

Mutation in Bullous Congenital Ichthyosiform Erythroderma (BCIE aka EHK aka epidermolytic ichthyosis) vs mutation in Congenital Ichthyosiform Erythroderma

Back 7

BCIE: AD defect in keratins 1 and 10

CIE: AR defect in transglutaminase 1, ALOX12B, ALOXE3, NIPAL4, PNPLA1

Front 8

Clinical presentation of Bullous Congenital Ichthyosiform Erythroderma vs Congenital Ichthyosiform Erythroderma at birth?

Back 8

BCIE (aka EHK): AD defect in keratins 1 and 10 --> widespread bullae, erosions and erythroderma at birth

CIE: AR defect in transglutaminase 1, ALOX12B, ALOXE3, NIPAL4, PNPLA1 --> collodion baby with ectropion and eclabium

Front 9

As patients with bullous congenital ichythosiform erythroderma (BCIE, EHK, EI) grow up, what do they look like? What about babies with congenital ichthyosiform erythroderma?

Back 9

BCIE (aka EHK): AD defect in keratins 1 and 10 --> widespread bullae, erosions and erythroderma at birth --> grow up with rough, hyperkeratotici skin, prone to infection, malodorous, macerated intertriginous areas, spares palms and soles (this has a keratin 10 defect)

CIE: AR defect in transglutaminase 1, ALOX12B, ALOXE3, NIPAL4, PNPLA1 --> collodion baby with ectropion and eclabium --> after infancy, intense redness, fine, flaky, white scale on trunk and arms

Front 10

Associations with x linked recessive ichthyosis?

Back 10

the C's!!!

Comma shaped corneal opacities

Cryptochidism

Cancer (testicular)

**remember, you will see a failure of labor with this** decreased placental sulfatase

Front 11

What is Ichthyosis hystrix Curth-Macklin? Mutation?

Back 11

remember, ichthyosis hystrix is a destrictipe term for massive hyperkeratosis with verrucous surface and porcupine like spines (seen in epidermolytic nevi, Curth Macklin, and hystrix like ichthyosis with deafness HID)

Curth Macklin is an AD mutation in Keratin 1 --> ridged appearance over joints and skin folds, digital flexion contractures

Front 12

What is ichthyosis en confetti? mutation?

Back 12

100s-1000s of small confetti like islands of normal skin in ichthyosis

AD keratin 10

Front 13

Ichthyosis bullosa of Siemens is a defect in what? Presentation?

What is the associated molting phenomenon?

Back 13

AD defect in Keratin 2e, 10 (so spares palms and soles)

similar to EHK/BCIE, but milder degree of bilstering, fragile blisters in early in life, later wtih hyperkeratotic plaques on elbows and kenes

Mauserung phenomenon-- superficial molting for peeling of skin

Front 14

DDX for Colloidian baby?

Back 14

Self healing colloidian baby

Lamellar ichthyosis

Congenital ichthyosiform erythroderma

Sjogren Larssen syndrome

Trichothyodystophy

Gaucher disease

Hay-Wells

Neutroal lipid storage disease

Conradi Hunermann Happle syndrome

Front 15

Mutation in lamellar ichthyosis?

Presentation?

Back 15

AR defect in transglutaminase 1 (65-90%)

Collodion baby at birth with ectropion, eclabium, erythroderma --> as a child/adult, will have large, plate-like scales, palmoplantar keratoderma, hypohydrosis (heat stroke)

Front 16

What disorders are associated with transglutaminases?

Back 16

Dermatitis Herpetiformis - epidermal transglutaminase 3

Lamellar ichthyosis - transglutaminase 1

Acral peeling skin syndrome - transglutaminase 5

Front 17

Gene defect in Harlequin Fetus? Clinical presentation and progression?

Back 17

AR ABCA12**- ATP binding cassette transporter family for lipid transport with resulting problem in profilaggrin --> filaggrin

Harlequin baby --> stillborn or most die within first 1-2 weeks, but then they peel off

Front 18

Gene defect in Sjogren Larsson Syndrome?

Back 18

AR wtih defect in fatty aldehyde dehydrogenase (ALDH3A2/FALDH)

Front 19

Presentation of Sjogren Larsson Syndrome?

Back 19

Hyperkeratosis and scale

Think of a Spastic Swed who can't See or Speak

MC in Sweden, spastic di/paraplegia (scissor gate), MR (speech difficulties), perifoveal glistening white dots (see)

Front 20

TOC for pruritis in Sjogren Larsson Syndrome?

Back 20

zileuton

Front 21

What is the gene defect in Refsum syndrome?

Back 21

Refsum syndrome (heredopathia atactica polyneuritoformis)

AR defect in PAHX and PEX7

*Deaf Ref- PAHX AND PEX

Front 22

Presentation of Refsum Syndrome?

Proposed Tx?

Back 22

Mild ichthyosis that starts later in life

ataxia, progressive peripheral polyneuropathy, retinitis pigmentosa (salt and pepper retina), deafness, CHF, arrhythmias, skeletal hyperostosis

A Deaf Ref (in a black and white uniform- salt and pepper retina) stumbled over and broke up the PHYTE, then cluched his PEX because he was having an arrhythmia

Front 23

Defect in Netherton Syndrome? Manifestations?

Back 23

SPINK5

Netherton SPINKs in her vaginata, no condom (no vernix)

Ichthyosis linearis circumflexa (serpiginous plaques with double edges scale along margins), trichorrhexis invaginata, anaphylacti food allergies with IgE

Front 24

Ichthyosis linearis circumflexa is a buzz word for...

Back 24

Netherton syndrome

Front 25

What is PIBIDS? Increased risk for?

Back 25

Photosensitivity

Ichthyosis

Brittle hair (trichothiodystrophy, tiger tail!)

Intellectual impairment

Decreased fertility

Short stature

If only hair findings and ichythosis but NO sensitivity, no increase risk of cancer

Front 26

Mutation in Chanarin Dorfman syndrome?

Back 26

AR defect in abhydrolase domain (ABHD5) --> lipid vacules in leukocytes

generalized fine white scale, erythroderma, a/w developmental delay, hepatomegally, myopathy, hearing impairment, cataracts

That Dorf is such a Doof! (developmental delay, hearing impariment, cataracts)

Front 27

Gene defect with Conradi Hunermann Happle syndrome? Inheritance pattern?

Back 27

Conradi Hunermann Happle- SLD defect in EBP gene leading to defect in cholesterold biosynthesis

Go in a childs happy face= happy

Front 28

Presentation of Conradi Hunermann Happle syndrome?

Back 28

chondrodysplasia punctata

asymmetric limb shortening

cataracts

Front 29

Bone Associations:

1. Osteopoikilosis

2. Polyostotic fibrous dysplasia

3. Stippled epiphysis

4. Osteopathia striata

Back 29

Bone Associations:

1. Osteopoikilosis- Buschke Ollendorff

2. Polyostotic fibrous dysplasia- McCune Albright

3. Stippled epiphysis- Conradi Hunermann Happle syndrome, CHILD, rhizomelic CDP (my CHILD Conrad)

4. Osteopathia striata- Golz (focal dermal hypoplasia)

Front 30

What is CHILD syndrome? Inheritance pattern?

Back 30

CHILD- congenital hemidysplasia with ichthyosiform erythroderma and limb defects

X linked dominant

NSDHL (no child in the NHL)

Front 31

What are the Erythrokeratodermas?

Back 31

Erythrokeratoderma variabilis

Progressive symmetric erythrokeratoderma

Keriatitis Ichthyosis Deafness (KID) syndrome

Front 32

What are the mutations in Erythrokeratoderma variabilis? Presentation?

Back 32

Erythrokeratoderma variabilis (Mendes da Costa)

AD defect in Connexin 31/30.3 (GJB3/4)

Erythemaout geographic patches- changes shape and position daily, worsensn til puberty, then enters a chronic, stable course

Mendes da Costa is my favorite coast line to visit! (geographic, coast, changing, work with me.)

Front 33

Progressive symmetric erythrokeratoderma is a mutation in ...

Back 33

Loricrin or connexin 30.0 (GJB4)

Front 34

What is the defect in KID syndrome? Presentation?

Back 34

AD defect in connexin 26 (GJB2) --> note, this is allelic to Vohwinkel

Keratitis- Ichthyosis- Deafness