Spitz Chapter 2 Do Of Pigmentation

Front 1

Tyrosinase negative Albinisim

Back 1

OCA Type 1

Front 2

Defect in OCA 1

Back 2

Tyrosinase

Front 3

Pathogenesis of OCA1

Back 3

Tyrosinase mutations --> lead to absent tyrosinase activity or lack of tyrosinase transport to melanosomes

Front 4

T/F Decreased number of melanocytes in OCA1

Back 4

False - normal number of melanocytes; cannot produced melanin

Front 5

Skin color in OCA1

Back 5

Pink white color

Front 6

Increased risk of skin cancer in OCA 1?

Back 6

Yes - SCC > BCC > MM

Front 7

Why do OCA1 patients have eye findings?

Back 7

Miswiring of optic fibers -->
nystagmus, photophobia, impaired visual acutity, strabismus,

Front 8

Color of eyes in OCA1?

Back 8

Blue to great cule irides

Front 9

Features of OCA1B

Back 9

Yellow mutant; minimal pigment and temperature sensitive albinism

Front 10

Tyrosinase positive albinism

Back 10

OCA2

Front 11

Inheritance and gene in OCA2

Back 11

AR; P gene

Front 12

What is most common form of albinism?

Back 12

OCA2

Front 13

What is the pathogenesis of OCA2?

Back 13

P Gene mutation --> decrease eumelanin synthesis
Gene product thought to play a role in tyrosinases tranport

Front 14

OCA2 is tyrosinase negative

Back 14

False - it has tyrosinase (tyr +)

Front 15

skin findings in OCA2

Back 15

generalized pink-white to cream color; multiple pigmented nevi, ephelides and lentigines
Solar keratoses
SCC and BCC

Front 16

How do the hair features in OCA1 differ from OCA2?

Back 16

Snow white hair in OCA1
Cream to yellow brown in OCA2

Front 17

Eye findings in OCA2

Back 17

Blue to yellow brown irides
Nystagmus, photophobia
Impaired VA, strabismus, foveal hypoplasia

Front 18

Inheritance and gene of Hermansky Pudlak Syndrome

Back 18

AR; HPS1 and AP3B1 for HPS2

Front 19

Most common gene in HPS?

Back 19

HPS1 found in NW Puerto rico and swiss village

Front 20

Result of mutations of HPS genes?

Back 20

HPS1 - important in localization via intracellular trafficking and organelle formation
AP3B1 (HPS2) - important in protein packaging, veiscular formation and membrane fusion within the cell

Front 21

Why do patients with HPS have a bleeding diasthesis?

Back 21

platelet storage pool defect with decreased ADP, ATP --> platelet aggregation

Front 22

What results from lysosomal membrane defect?

Back 22

accumulation of ceroid lipofuscin in macrophages within lung and GI tract.

Front 23

Skin findings that differentiate HPS from OCAs

Back 23

Pigment dilution
Ecchymoses and petechiae

Common findings - pigmented nevi, solar keratoses, SCC, BCC

Front 24

Color of hair in HPS?

Back 24

Cream to red brown hair
(Without silvery sheen C2 CHS)

Front 25

T/F HPS has similar eye findings as OCA1 and 2

Back 25

True - photophobia, nystagmus, decr VA, strbismus, foveal hypoplasia

Front 26

Name the lymphohistiocytic findings in HPS.

Back 26

1) Lung - Pulmonary fibrosis
2) GI tract - granulomatous colitis
3) Heart - cardiomyopathy

Front 27

What causes the lyphohistiocytic findings in HPS?

Back 27

ceroid deposition in macrophages

Front 28

Lab abnormalities in HPS?

Back 28

Prolonged Bleeding time
Normal PT/PTT and platelet count

Front 29

Name the microscopy finding of HPS

Back 29

platelets without dense granules

Front 30

What should HPS patients avoid?

Back 30

ASA and PG synthesis inhibitors

Front 31

Who is a tyrosinase positive albino?

Back 31

HPS patients

Front 32

What percentage of HPS patients develop symptomatic pulmonary fibrosis?

Back 32

33%

Front 33

Inheritance and gene for chediak higashi.

Back 33

AR; LYST

Front 34

What does the lyst gene encode for?

Back 34

For Chediak Higashi
Lyst -->encoudes for lysosomal tracking protein that Microtubule mediated lysosmal fusion/fission and protein sorting.

Front 35

What does the mutation in lyst result in?

Back 35

Accumulation of giant lysosomal granules in a variety of cells:
PMNs - defective phagocytosis, decreased chemotaxis
Melanocytes - pigmentary dilution
Neurons - Progressive neurologic deterioration
Plately diesthesis
Decreased NK cell and AB dependent cytolysis

Front 36

Skin color and hair color in chediak higashi

Back 36

slate gray to light cream color skin

light blonde color with silver sheen

Front 37

T/F CHS have recurrent bacterial infections.
How does it manifest?

Back 37

True - M/C Staph
recurrent sinusitis, pneumonia

Front 38

Which two syndromes have an accelerated hematologic phase?

Back 38

CHS
Griscelli

Front 39

What is the accelerated phase?

Back 39

lymphohistiocytic proliferation with infiltration of liver, spleen, and LN

Has assoc anemia, netopenia, TCP

Front 40

Eye findings in chs.

Back 40

photophobia; strabismus, nystagmus, decreased uveal pigment

Front 41

How can you diagnose CHS in lab?

Back 41

CBC checking for giant granules in neuts.

Front 42

T/F platelet storage pool defect in CHS is less than in hPs

Back 42

true

Front 43

INheritance and genes of griscelli syndrome?

Back 43

AR; genes myosin Va or RAB27a

Front 44

What are the genes in griscelli syndrome involved with?

Back 44

Proteins are involved in organelle trafficking and membrane transport

Front 45

A small portion of griscelli patient have what gene mutation?

Back 45

melanophilin

Front 46

Hair and skin color in griscelli.

Back 46

silver gray hair eyebrows, lashes

Pigmentary dilution

Front 47

What makes the heme findings different in griscelli syndrome?

Back 47

neutropenia and tcp without leukocyte inclusions

Front 48

Name immunologic abnormality in griscelli

Back 48

Combined T and B cell immunodef --> pyogenic infections; HSM; accelerated lymphoma like phase

Front 49

CNS findings in CHS.

Back 49

progressive neuro deterioration with ataxia,, m. weakness, and sensory loss

Front 50

Neuro findings in griscelli? T/F

Back 50

True - progressive deterioration with hypotonia, psychomotor retardation, sz

Front 51

Light microscopy finding in Griscelli

Back 51

uneven clumps of mlanin in medulla of hair shaft (C2 CHS - even small clumps)

Front 52

CBC findings in griscelli

Back 52

absent cytoplasmic inclusion bodies in neuts

Front 53

Difference between phentype seen in griscelli gene mutations.

Back 53

MYO5a - neuro impairment without hemophagocytic syndrome

RAB27A - hemophagocytic syndrome with secondary CNS involvement

Front 54

Ejalde syndrome gene defect

Back 54

myosin Va (allelic to griscelli)

Front 55

Clinical Fx of ejalde

Back 55

silvery hair
severe neuro
No immunodeficiency or hemophagocytosis
Large irregular distribution of melanosomes

Front 56

Piebaldism inheritance and gene defect

Back 56

AD; C kit

Front 57

What does the gene defect of piebaldism result in?

Back 57

ckit mutation results in abnormal TK transmembrane Receptors --> abnormal melanocyte embryogenesis with defecctive melanoblast prolif, migration, and distribution

Front 58

Characteristic finding in piebaldism

Back 58

white forelock 80-90%

Front 59

Inheritance and genes of waardenburg syndrome

Back 59

AD; Pax (1 and 3), MITF (2), Sox10 and endothelin (4)

Front 60

Pathogenesis of gene causing waardenburg 1 and 3

Back 60

PAX3 --> txn factor that controls neural crest differentiation and reg tx of other genes downstream

Front 61

Pathogenesis of gene causing waardenburg 2

Back 61

MITF --> melanocyte txn factor

Front 62

Pathogenesis of gene causing waardenburg 4

Back 62

SOX10, endothelin, and endothelin R gene mutations

Front 63

T/F patient with waardenburg have depigmented patches

Back 63

T

Front 64

Hair findings in waardenberg

Back 64

Synophry (70%) white forelock (< 50%)

Front 65

Nose finding in waardenberg

Back 65

Broad nasal root (80%)

Front 66

Which waardenburg does not have dystopia canthorum?
WHat is it?

Back 66

Not in 2 but in 99%
Lateral displacement of medial canthi with normal interpupillary distance

Front 67

% with heterochromic irides

Back 67

25%

Front 68

Congenital SNHL is most common in which waardenburg?

Back 68

II
about 20%

Front 69

which waardenburg has hirschprung dz?

Back 69

< 5%; type IV

Front 70

Eponym for hypomelanosis of ito.

Back 70

incontinentia pigmenti achromians

Front 71

T/F Inheritance of hypomelanosis of ito is AD.

Back 71

False - not inherited

Front 72

Findings of hypomelanosis of ito

Back 72

Marble cake hypopigmentation in blaschkos lines
alopecia
CNS - sz
Eyes - striabismus and hypertelorism
MS - scoliosis and lim length discrepancy
Teeth - anodontia

Front 73

Block Sulzberger

Back 73

IP

Front 74

What is the inheritance and gene of IP?

Back 74

XLD; Nemo

Front 75

In IP, 97% of survivors are female. What are male survivors thought to have?

Back 75

Klinefelter

Front 76

What is the function of gene mutated in IP?

Back 76

NEMO --> NFkappa beta modulator --> defective activation
of txn factor essential for several inflamm, immune and apoptotic pw

Front 77

Nail, hair and teeth findings....in IP

Back 77

Hair - scarring alopecia
Nails - dystrophic changes
Teeth - anodontia, peg conical teeth

Front 78

Eye and CNS findings in IP.

Back 78

Eye - strabismus, cataracts, optic atrophy, retinal vascular changes

CNS (30%)
Sz, MR, spastic pearalysis

Front 79

T/F IP patient have early death.

Back 79

False - normal life span

Front 80

Inheritance of gene of LEOPARD syndrome

Back 80

AD; PTPN11 gene

Front 81

Eponym for LEOPARD

Back 81

Lentigines - generalize; mucosa spared
ECG conduction defects
Ocular hypertelorism
Pulmonic stenosis
Abonormal Genitalia
Retardation of Growth
Deafness (SN)

Front 82

Pathogenesis of Leopard

Back 82

Defect in PTPN11 --> encodes nonreceptor protein tyrosine phosphatase SHP2 --> implicated in Noonan

Front 83

Genoderm implicated by gene defect of Leopard

Back 83

PTPN11

Noonan

Front 84

Craniofacial defects in LEOPARD

Back 84

ocular hypertelorism
Triangular facies

Front 85

Normal or shortened life span in leopard?

Back 85

Normal

Front 86

CARNEY Complex Inheritance, eponym, gene

Back 86

AD; NAME and LAMB; PRKaR1A

Front 87

What does the gene defect in Carney complex cause?

Back 87

Tumor suppressor encoding the regulatory subunit type 1A of protein kinase A isolated in half the cases

Front 88

NAME =

Back 88

Nevi - blue and melanocytic
Atrial myxomas
Myxomas
Ephelids ( can be on mucosa)

Front 89

Name the endocrine abnormalities found in carney?

Back 89

Pigmented nodular adrenocoritical dz - Cushing
Pituitary Adnoma - acromegaly

Front 90

Two other non endocrine tumors seen in Carney.

Back 90

Testicular tumors
Psammomatous melanotic schwannomas

Front 91

Treatment of atrial myxomas.

Back 91

excision

Front 92

Bone findings of mccune-albright syndrome

Back 92

polyostotic fibrous dysplasia --. recurrent fx

Front 93

Endocrine findings of Mccune albright?

Back 93

Precocious purberty;
20-30% hyperthyroidism

Front 94

Eponym for NF1

Back 94

Von Recklinghausen Dz

Front 95

Inheritance and gene for NF1

Back 95

AD; Spontaneous in 50%

Front 96

Pathogenesis of NF1

Back 96

Neurfibromin is a Tumor suppresor that dampens products of ras proto-oncogenes

Front 97

Which is most common form of NF?

Back 97

NF1

Front 98

For CALMs, number that suggests NF1

Back 98

Greater than 6

Front 99

Eye findings in NF1

Back 99

Lisch nodules - 90% patients > 6 yo; congenital glaucoma

Front 100

Skeletal findings of NF1

Back 100

Sphenoid wing dysplasia
macrocephaly
scoliolsis

Front 101

What is important to check (VS) in NF1 patients?

Back 101

Blood pressure --> pheo or RAS

Front 102

Dx of NF1 (Consensus)

Back 102

6 or more CALMFS > 5mm in prepubertal and over 15mm in post pubertal
2+ NF or one plexiform
Freckling in the axillary or inguinal region
Optic glioma
2+ lisch nodules
distinctive osseous lesion - sphenoid wingl dysplasia or thinning of long bone cortex
first degree relative with NF1

Front 103

Inheritance and gene of NF2

Back 103

AD; SCH - shwnnomin/merlin protein product --> affects tumor suppressor

Front 104

NF and CALM are less or more common in NF2

Back 104

Less common

Front 105

Eye finding of NF2

Back 105

Juvenile posterior subcapsular lenticular opacity

Front 106

Characteristic tumor of NF2

Back 106

B/l vestibular schwannomas (acoustic schwannoma)
may be complicated by deafness, tinnitus and poor balance

Front 107

Tuberous sclerosis eponym, genes, and inheritance

Back 107

Bourneville's syndrome; epiloia
AD
TSC1 and TSC2

Front 108

Products of the TS genes

Back 108

TSC1 hamartin, TSC2 tuberin --> tumor suppression and interact to reg GTPas activity

Front 109

Most common type of macule?

Back 109

Polygonal

Front 110

Most characteristic and earliest finding?

Back 110

ash leaf macule

Front 111

Name the CNS findings in TS.

Back 111

Spasms, sz, MR, paraventricular calcification

Front 112

Kidney findings of TS

Back 112

angiomyolipoma, cysts

Front 113

Cardiac TS

Back 113

rhabdomyoma

Front 114

Findings of lungs in TS

Back 114

Lympha\gniomyomatosis

Front 115

Any involvement of mouth in TS?

Back 115

yes, enamel pits, gingival fibromas

Front 116

Another facial finding of TS?

Back 116

fibrous plaque of face