Inherited pigmentary disorders

Question 1

List inherited disorders hypopigmentation

Answer 1

Pigment Wasn’t On High Crazy Charlie Got Half Inside

• piebaldism, Waardenburg (melanocyte migration)
• OCA (melanin synthesis)
• Hermansky pudlak, Chediak Higashi, Cross (melanosome biogenesis)
• Griscelli (melanosome transport)
• Hypomelanosis of Ito (mosaicism)

Question 2

List inherited disorders of hyperpigmentation

Answer 2

Fathers Insist Lovely Daughters Never Date RanK Fanta Pants w Dark Digits

• Familial progressive hyperpigmentation
• IP
• Linear + whorled naevoid hypermelanoais
• Dowling-Degos / Galli Galli
• Naegelli-Francheschetti-Jadassohn
• Dyskeratosis Congenita
• Reticular acropigmentation of Kitamura
• Fanconi Anaemia
• Peutz Jeghers
• Dyschromatosis (symmetrica hereditaria/ universalis hereditaria)

Question 3

Piebaldism

- inheritance, features

Answer 3

AD (KIT mutations)

white forlock, midline/ventral depigmentation, areas of hyperpigmentation

Question 4

Waardenburg

• inheritance
• types + features

Answer 4

AD inheritance
PAX 3 MITtens + 10 SOX 
- PAX3, MITF, SOX10
- type 1 - classic (white forlock, hypopigmentation, heterochromia, dystopia canthorum, deafness, mild MSK)
- type 2 - more deaf, less eye changes
- type 3 - more MSK
- type 4 - hirschsprung

Question 5

DDx for circumscribed scalp poliosis

Answer 5

Acquired
- vitiligo, drug induced (latanoprost, imiquimod, tyrosine kinase inhibitors), trauma, post-inflammatory, alopecia areata, halo naevus, Vogt-Koyanagi-Harada, Alezzandrini, melanoma-associated leukoderma

Genetic
- Piebaldism, Waardenburg, TS, angora hair naevus, naevus comedonicus

Question 6

Types of OCA

- inheritance

Answer 6

7 types
OCA 1A - complete lack of tyrosinase
OCA 1B - temperature sensitive mutation (can have darker hairs on cooler sites)
Types 2-7
Almost all AR

Question 7

Hermansky-Pudklak features

Answer 7

Disorder of melanosome synthesis
Dilution of hair/eye/skin pigmentation
Bleeding diathesis
Interstitial pulmonary fibrosis
Granulomatous colitis

Question 8

Chediak Higashi

Answer 8

Disorder of melanosome synthesis
Dilution of hair/skin/eyes pigment
Immune dysfunction
Bleeding diathesis
Neurological (cerebellar syndrome)

Question 9

Cross syndrome

Answer 9

South African

Pigment dilution

Question 10

Griscelli Syndrome

Answer 10

Disorder of melanosome transport
Hair + skin pigment dilution
Neurological changes
immunological dysfunction

Question 11

Woolf syndrome

Answer 11

Deaf WOOOOOOOLF

congenital deafness + partial OCA

Question 12

Hypomelanosis of Ito

Answer 12

mental retardation
skeletal anomalies 
linear naevoid hypopigmentation 
chromosomal mosaicism
Extracutaneous occurs in 15%

Question 13

DDx CALMS

Answer 13

MMaFS BITCH GANG
Maffucci, McCune Albright, Fanconi anaemis, Bloom syndrome, Idiopathic, TS, Chediak Higashi, Gorlin, Ataxia telangiectasia, NF, Gaucher

Question 14

DDx linear hypopigmentation

Answer 14

CHIILL MEG (Blaschkoid distribution)
- Conradi, hypomelanosis of Ito, IP, Lichen striatus, lichen sclerosus, menkes, epidermal naevus, Goltz

Question 15

DDx guttate leukoderma

Answer 15

Idiopathic guttate hypomelanosis
Confetti spots in TS
PLC
LS
vitiligo
Darier disease
XP
pityriasis alba
tinea versicolor
leukoderma punctata - after PUVA

Question 16

Incontinentia Pigmenti

• inheritance + gene
• histology

Answer 16

XLD (lethal in males)
IKBKG (same gene hypohidrotic ectodermal dysplasia w immunodef)
Histo - early eosinophilic spongiosis –> acanthosis + dyskeratosis –> pigment incontinence, basal vacuolation –> epidermal atrophy, loss adnexal structures

Question 17

Incontinentia pigmenti

- clinical features - cutaneous

Answer 17

Stage 1 vesiculobullous - present at birth/ first 2 weeks
Stage 2 verrucous - within first few months
Stage 3 hyperpigmented - occurs within first year (minority can be born in this stage)
stage 4 hypopigmented - adolescence through adulthood

Question 18

Incontinentia pigmenti

- clinical features - extracutaneous

Answer 18

malignancy risk - rhabdomyosarcoma, paratesticular, retinoblastoma, leukaemia, Wilm’s tumour
Teeth - delayed, cone-shaped
Eyes - strabismus, cataracts, microphthalmia
Nails - onychodystrophy
Hair - cicatricial alopecia
CNS - seizures, microcephaly, intellectual impairment
MSK - skull/scoliosis

Question 19

Reticulate hyperpigmentation DDx

Answer 19

Dowling Degos / Galli Galli
Naegelli-Franchescetti-Jadasshon
Dyskeratosis Congenita
Fanconi Anaemia
Reticulate acropigmetnation of Kitamura
Confluent + reticulated papillomatosis (Gougerot + Carteaud)
Erythema ab igne
Prurigo pigmentosa (Keto diet)
Atopic dirty neck
Pityriasis versicolor
PIH

Question 20

Dyskeratosis congenita features

Answer 20

PPK (diffuse)
Leukoplakia
Reticulate pigmentation chest/neck/prox limbs)
Nail dystrophy
BM dysplasia

Question 21

Fanconi anaemia

Answer 21

more generalised hyperpigmentation (less reticulate compared to DC)
CALMs can be present
Haem changes 
Increased risk cancers
Short stature