disorders of cornification

Question 1

ichthyosis vulgaris defect

Answer 1

profilaggrin synthesis defect –> decreased profilaggrin in keratinocytes –> retention hyperkeratosis
decreased filaggrin –> transepidermal H2O loss

Question 2

ichthyosis vulgaris presentation (4) and histo

Answer 2

1) fine white translucent scale sparing flexures
2) hyperlinear palms
3) KP
4) atopic triad with hayfever and asthma
histo: absent granular layer

Question 3

x-linked ichthyosis defect

Answer 3

steroid sulfatase deficiency –> accumulation cholesterol-3 sulfate in epidermis –> inhibition transglutaminase 1

Question 4

x-linked ichthyosis presentation (5) and histo

Answer 4

1) halted labor
2) 2-6 wks old mild erythrodermal and exfoliation –> brown adherent scale
3) preauricular involvement, dirty neck
4) corneal opacities
5) cryptochidism
histo: normal - thickened granular layer

Question 5

epidermolytic hyperkeratosis psuedonyms

Answer 5

bullous congenital ichthyosiform erythroderma

bullous ichthyosis

Question 6

epidermolytic hyperkeratosis defect

Answer 6

50% AD & sporadic
keratins K1 and K10 on genes 12q and 17q
(only K1=PPK, only K10=spares palms/soles)

Question 7

clumped keratin filaments on electron microscopy at 20-22 wks GA

Answer 7

epidermolytic hyperkeratosis

Question 8

epidermolytic hyperkeratosis presentation (4)

Answer 8

1) newborn w/ widespread bullae & erythroderma
2) hyperkeratosis with dark warty scales in flexures
3) PPK
4) secondary infections (staph) & foul odor

scales shed full-thickness SC –> denuded base

Question 9

lamellar ichthyosis defect

Answer 9

AR transglutaminase 1 (also ABCA12, CYP4F, NAP14)

–> defective cross-linking of involucrin –> defective cornification & desquamation

Question 10

lamellar ichthyosis precentation (5) and findings on EM

Answer 10

1) collodion baby
2) large dark plate-like scale increased in flexures
3) scarring alopecia
4) hypohydrosis
5) PPK & nail dystrophy
EM: lipid vacuoles in corneocytes

Question 11

congenital ichthyosiform erythroderma defect

Answer 11

AR heterogeneous (ALOX12 B gene, ALOXE3, transglutaminase 1, ichthyin, NEPL4, ABCA12, PNPLA1)
--> accelerated epidermal cell turnover rate

Question 12

congenital ichthyosiform erythroderma presentation (5)

Answer 12

1) collodion baby
2) generalized erythroderma with fine white scale involving flexures
3) cicatricial alopecia
4) ectropion
5) heat intolerance

Question 13

harlequin fetus defect

Answer 13

AR heterogeneous (ABCA12) also de novo deletion 18q21
defective keratinization & hyperkeratosis
lipid accumulation in stratum corneum
defective profilaggrin

Question 14

harlequin fetus presentation

Answer 14

1) collodion baby w/ ectropion & eclabium

2) hyperkeratotic plates w/ deep fissures

Question 15

sjögren-larsson syndrome defect

Answer 15

AR fatty aldehyde dehydrogenase (FALDH)

defective conversion fatty alcohol to fatty acid –> defective catabolism phospholipids and sphingolipids –> fatty alcohol, fatty aldehyde, and leukotriene B4 build up

Question 16

sjögren-larsson syndrome presentation (4S’s + 3)

Answer 16

4 S’s in name
Stupid
Spastic/speech problems
Scissor gait
Seizures
ö = glistening perimacular white dots (retinal pigment degeneration) = pathognomonic
also itchy ichthyosis and dental dysplasia

Question 17

refsum syndrome defect

Answer 17

AR PAHX on ch10p and PEX7 on ch6q

Ref them up - pahx and pex

Question 18

refsum syndrome presentation (6)

Answer 18

RAPID
retinitis pigmentosa
ataxia
peripheral neuropathy
ichthyosis
deafness (sensorineural)

You get into a phyt (phytanic acid) when you Ref them up, Pahx and Pexz to the heart (arrhythmia & heart block) and brain and pour salt & pepper into the eyes

Question 19

refsum syndrome lab abnormality and treatment

Answer 19

increased serum phytanic acid
lipid-filled vacuoles in basal keratinocytes
dietary restriction of green veggies, dairy, ruminant fats

Question 20

conradi-hünermann syndrome defect

Answer 20

XLD emopamil-binding protein on chXp11

Question 21

conradi-hünermann syndrome presentation (4)

Answer 21

lethal in males

1) patchy alopecia
2) short stature
3) chondrodysplasia punctata (ü) & asymmetric limb shortening
4) ichthyosiform erythroderma in blaschko’s lines –> follicular atrophoderma & hyperpigmentation

Question 22

CHILD syndrome pneumonic

Answer 22

Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects

Question 23

CHILD syndrome defect

Answer 23

XLD NSDHL gene on Xq28
(DHL delivery delivering a CHILD)
–> defective cholesterol biosythesis

Question 24

CHILD syndrome presentation (3)

Answer 24

1) ichthyosiform erythroderma & alopecia
2) ipsilateral limb deformity & organ hypoplasia
3) stippled epiphyses

Question 25

netherton syndrome pseudonym

Answer 25

ichthyosis linearis circumflexa

Question 26

netherton syndrome defect

Answer 26

AR SPINK5 gene on ch5q32

gene encodes LEKT1 (serine protease inhibitor) - important for down-regulating inflammation, linked to atopy

Question 27

netherton syndrome presentation (4)

Answer 27

1) generalized erythema & hypernatremia at birth
2) ichthyosis linearis circumflexa with double edged scale
3) trichorrhexis invaginata (bamboo hairs)
4) atopy and seborrheic-like scale

Question 28

netherton syndrome associated risks (4)

Answer 28

1) anaphylactic rxn to foods
2) HPV
3) SCC
4) increased risk infections

Question 29

erythrokeratoderma variabilis defect

Answer 29

AD GJB3 or GJB4 gene

encodes for connexin 31 and 30.3

Question 30

erythrokeratoderma variabilis pseudonym

Answer 30

mendes da costa syndrome

Question 31

erythrokeratoderma variabilis presentation (2)

Answer 31

1) migratory erythematous patches

2) fixed focal hyperkeratotic plaques

Question 32

KID syndrome pneumonic

Answer 32

Keratitis-Ichthyosis-Deafness syndrome

Question 33

KID syndrome defect

Answer 33

AD and AR (90% sporadic)
GJB2 gene encodes connexin 26
(also GJB6 - connexin 30)

Question 34

KID syndrome presentation (6+risks)

Answer 34

1) erythroderma at birth
2) erythematous keratotic plaques
3) stippled palmoplantar keratoderma
4) non-scarring alopecia
5) photophobia –> vascularized keratitis –> blindness
6) sensorineural deafness
also bacterial/fungal infections, SCC, pilar tumors/cysts

Question 35

diffuse palmoplantar keratoderma defect

Answer 35

AD
Vörner = keratin genes 9 and 1 (german)
Unna-Thost: keratin gene 1

Question 36

diffuse palmoplantar keratoderma presentation (4)

Answer 36

birth to 1 yr

1) hyperkeratosis palms and soles w/ white-yellow hue & erythematous border and desquamation
2) no transgrediens (do not cross Weber’s line)
3) hyperhidrosis +/- bromhidrosis
4) painful fissuring