pigmentary disorders

Question 1

oculocutaneous albinism

Answer 1

OCA1a - no pigment skin/hair
OCA1b - no pigment skin/hair, but time & low temperature may lead to pigment development in some areas 
OCA2 - light brown hair, most common***
OCA3 - red hair 
OCA4 - seen in Japanese, like OCA2

OCA1a/b —> TYR
OCA2 –> OCA2, may be seen in Angelman or Prader Willi, MOST COMMON
OCA3 —> TYRP1
OCA4 –> SLC45A2

Question 2

silvery hair syndrome

Answer 2

chediak-higashi, elejalde syndrome, and griscelli.

All of these are ARecessive

Question 3

griscelli

Answer 3

GS1 - neurologic impairment, MYO5A
GS2 - immunodeficiency, RAB27A
GS3 - skin only, MLPH

Question 4

chediak-higashi

Answer 4

defect in LYST gene

multisystem disorder including skin + blood diathesis + silvery hair + oculocutaneous albinism + neuro defect

death typically occurs by age 10

Question 5

elejalde syndrome

Answer 5

similar to GS1

Question 6

Hermansky-Pudlak syndrome

Answer 6

Autosomal Recessive (AR)
a/w HPS1 gene and more
oculocutaneous albinism + bleeding diathesis + buildup of ceroid lipofuscin
more common in puerto ricans (#1 cause of death: pulmonary fibrosis)
p/w ecchymoses, nosebleeds, menorrhagia, photophobia
complications –> gran colitis, pulm fibrosis, cardiomyopathy, and renal failure

Question 7

Piebaldism

Answer 7

AD
defect in c-KIT gene
presents with white forelock (poliosis), leukoderma, no internal issues

Question 8

Waardenburg syndrome

Answer 8

AD
presents with white forelock (poliosis) + internal issues
W1 white forelock, dystopia canthorum, heterochromia irides, deafness
W2 deafness
W3 upper limb abnormality
W4 hirschprung disease

Question 9

McCune Albright syndrome

Answer 9

NON-INHERITED somatic mutation in GNAS1 gene
p/w triad: cafe au lait macules + polyostotic fibrous dysplasia + endocrine dysfunction (e.g. hypophosphatemic rickets, precocious puberty, infantile Cushing syndrome)

Question 10

reticulate acropigmentation of kitamura

Answer 10

ADominant
ADAM10 gene defect
p/w reticulated pattern on the dorsal hands/feet

Question 11

Dowling degos disease

Answer 11

ADominant 
keratin 5 gene defect 
p/w reticulated hyperpigmentation of the axillae, groin, trunk 
a/w EBS with mottled pigmentation
Subtype - galli-galli disease

Question 12

lentiginoses syndromes

Answer 12

LEOPARD syndrome 
carney complex (NAME, LAMB) 
peutz-jeghers syndrome 
laugier-hunziker syndrome 
Cronkhite-canada syndrome
centrofacial lentiginosis 
bannayan-riley ruvalcaba

Question 13

dyschromatosis symmetrica hereditaria

Answer 13

ADominant
ADAR (SRAD) gene defect
p/w dyschromia on face and/or extremities
seen in Japanese/chinese patients, often by age 6

Question 14

dyschromatosis universalis hereditaria

Answer 14

ADominant
ABCB6 gene defect
p/w generalized dyschromia, pterygium
may be a/w short stature, idiopathic torsion dystonia, x linked ocular albinism, photosensitivity, neurosensory hearing loss

Question 15

dyskeratosis congenita

Answer 15

AD, AR, XLR
TERT(AR), TERC (AD), DKC1 (XLR)

p/w bone marrow failure, skin dyschromia, oral leukoplakia, and onychodystrophy

cause of death: bone marrow failure, pulmonary fibrosis, malignancy

Average age of death: 16 yo

Question 16

naegeli-franceschetti-jadassohn syndrome NFJS

Answer 16

TRANSIENT dyschromia + dental issues (e.g. early loss of teeth)

Question 17

dermatopathia pigmentosa reticularis DPR

Answer 17

PERSISTENT dyschromia + alopecia.

Question 18

Epidermal Bullosa

further classified as simplex (epidermal), junctional (BMZ), dystrophic (lamina densa), and kindler (mixed levels)

Answer 18

Simplex -> localized, generalized severe, generalized intermediate, muscular dystrophy (AR), mottled pigmentation. All others are AD
Gene: keratin 5/14, plectin** for muscular dystrophy

Junctional -> generalized severe, generalized intermediate, pyloric atresia. All are AR
Gene: Laminin
*JEB severe - hoarse cry at birth, death within first few years from pulmonary failure OR sepsis

Dystrophic -> dominant (DDER, AD), recessive generalized intermediate(RDEB, AR), recessive generalized severe (RDEB, AR). Gene: COL7A1
*RDEB generalized severe - mitten deformities, limb contractures, SCC is #1 cause of death

Kindler -> skin fragility, photosensitivity, poikiloderma (AR)
Gene: FERMT1

Question 19

lentiginosis syndromes

Answer 19

LEOPARD syndrome 
carney complex (NAME, LAMB) 
peutz-jeghers syndrome 
laugier-hunziker syndrome 
Cronkhite-canada syndrome
centrofacial lentiginosis 
bannayan-riley ruvalcaba

Question 20

LEOPARD syndrome

Answer 20

AD
PTPN11/SHP2 gene defect
lentigines, EKG, ocular hypertelorism, pulmonary stenosis, abnormal genital, growth retardation, deafness

Question 21

carney complex (NAME, LAMB)

NAME - nevi, atrial myxoma, ephelides
LAMB - lentigo, atrial myxoma, blue rubber nevus

Answer 21

AD

PRKAR1A gene defect

Question 22

peutz-jeghers syndrome

Answer 22

AD
STK11/LBK1 gene defect
pigmented spots on lips + GI polyps (a/w GI cancers)

Question 23

laugier-hunziker syndrome

Answer 23

pigmented spots on lips, genitalia

Question 24

Cronkhite-canada syndrome

Answer 24

lentigines of hands/feet, buccal mucosa
nail dystrophy
alopecia
intestinal polyps

Question 25

centrofacial lentiginosis

Answer 25

lentigines on nose and cheeks 
sacral hypertrichosis 
developmental delay 
seizures 
dwarfism 
endocrine dysfunction

Question 26

bannayan-riley ruvalcaba

Answer 26

PTEN defect

penile lentigines, lipoma, macrocephaly, developmental delay