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116 Cards in this Set
- Front
- Back
Tyrosinase negative Albinisim
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OCA Type 1
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Defect in OCA 1
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Tyrosinase
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Pathogenesis of OCA1
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Tyrosinase mutations --> lead to absent tyrosinase activity or lack of tyrosinase transport to melanosomes
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T/F Decreased number of melanocytes in OCA1
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False - normal number of melanocytes; cannot produced melanin
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Skin color in OCA1
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Pink white color
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Increased risk of skin cancer in OCA 1?
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Yes - SCC > BCC > MM
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Why do OCA1 patients have eye findings?
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Miswiring of optic fibers -->
nystagmus, photophobia, impaired visual acutity, strabismus, |
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Color of eyes in OCA1?
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Blue to great cule irides
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Features of OCA1B
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Yellow mutant; minimal pigment and temperature sensitive albinism
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Tyrosinase positive albinism
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OCA2
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Inheritance and gene in OCA2
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AR; P gene
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What is most common form of albinism?
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OCA2
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What is the pathogenesis of OCA2?
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P Gene mutation --> decrease eumelanin synthesis
Gene product thought to play a role in tyrosinases tranport |
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OCA2 is tyrosinase negative
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False - it has tyrosinase (tyr +)
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skin findings in OCA2
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generalized pink-white to cream color; multiple pigmented nevi, ephelides and lentigines
Solar keratoses SCC and BCC |
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How do the hair features in OCA1 differ from OCA2?
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Snow white hair in OCA1
Cream to yellow brown in OCA2 |
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Eye findings in OCA2
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Blue to yellow brown irides
Nystagmus, photophobia Impaired VA, strabismus, foveal hypoplasia |
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Inheritance and gene of Hermansky Pudlak Syndrome
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AR; HPS1 and AP3B1 for HPS2
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Most common gene in HPS?
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HPS1 found in NW Puerto rico and swiss village
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Result of mutations of HPS genes?
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HPS1 - important in localization via intracellular trafficking and organelle formation
AP3B1 (HPS2) - important in protein packaging, veiscular formation and membrane fusion within the cell |
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Why do patients with HPS have a bleeding diasthesis?
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platelet storage pool defect with decreased ADP, ATP --> platelet aggregation
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What results from lysosomal membrane defect?
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accumulation of ceroid lipofuscin in macrophages within lung and GI tract.
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Skin findings that differentiate HPS from OCAs
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Pigment dilution
Ecchymoses and petechiae Common findings - pigmented nevi, solar keratoses, SCC, BCC |
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Color of hair in HPS?
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Cream to red brown hair
(Without silvery sheen C2 CHS) |
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T/F HPS has similar eye findings as OCA1 and 2
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True - photophobia, nystagmus, decr VA, strbismus, foveal hypoplasia
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Name the lymphohistiocytic findings in HPS.
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1) Lung - Pulmonary fibrosis
2) GI tract - granulomatous colitis 3) Heart - cardiomyopathy |
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What causes the lyphohistiocytic findings in HPS?
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ceroid deposition in macrophages
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Lab abnormalities in HPS?
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Prolonged Bleeding time
Normal PT/PTT and platelet count |
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Name the microscopy finding of HPS
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platelets without dense granules
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What should HPS patients avoid?
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ASA and PG synthesis inhibitors
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Who is a tyrosinase positive albino?
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HPS patients
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What percentage of HPS patients develop symptomatic pulmonary fibrosis?
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33%
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Inheritance and gene for chediak higashi.
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AR; LYST
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What does the lyst gene encode for?
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For Chediak Higashi
Lyst -->encoudes for lysosomal tracking protein that Microtubule mediated lysosmal fusion/fission and protein sorting. |
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What does the mutation in lyst result in?
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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 |
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Skin color and hair color in chediak higashi
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slate gray to light cream color skin
light blonde color with silver sheen |
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T/F CHS have recurrent bacterial infections.
How does it manifest? |
True - M/C Staph
recurrent sinusitis, pneumonia |
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Which two syndromes have an accelerated hematologic phase?
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CHS
Griscelli |
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What is the accelerated phase?
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lymphohistiocytic proliferation with infiltration of liver, spleen, and LN
Has assoc anemia, netopenia, TCP |
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Eye findings in chs.
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photophobia; strabismus, nystagmus, decreased uveal pigment
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How can you diagnose CHS in lab?
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CBC checking for giant granules in neuts.
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T/F platelet storage pool defect in CHS is less than in hPs
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true
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INheritance and genes of griscelli syndrome?
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AR; genes myosin Va or RAB27a
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What are the genes in griscelli syndrome involved with?
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Proteins are involved in organelle trafficking and membrane transport
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A small portion of griscelli patient have what gene mutation?
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melanophilin
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Hair and skin color in griscelli.
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silver gray hair eyebrows, lashes
Pigmentary dilution |
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What makes the heme findings different in griscelli syndrome?
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neutropenia and tcp without leukocyte inclusions
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Name immunologic abnormality in griscelli
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Combined T and B cell immunodef --> pyogenic infections; HSM; accelerated lymphoma like phase
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CNS findings in CHS.
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progressive neuro deterioration with ataxia,, m. weakness, and sensory loss
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Neuro findings in griscelli? T/F
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True - progressive deterioration with hypotonia, psychomotor retardation, sz
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Light microscopy finding in Griscelli
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uneven clumps of mlanin in medulla of hair shaft (C2 CHS - even small clumps)
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CBC findings in griscelli
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absent cytoplasmic inclusion bodies in neuts
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Difference between phentype seen in griscelli gene mutations.
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MYO5a - neuro impairment without hemophagocytic syndrome
RAB27A - hemophagocytic syndrome with secondary CNS involvement |
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Ejalde syndrome gene defect
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myosin Va (allelic to griscelli)
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Clinical Fx of ejalde
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silvery hair
severe neuro No immunodeficiency or hemophagocytosis Large irregular distribution of melanosomes |
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Piebaldism inheritance and gene defect
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AD; C kit
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What does the gene defect of piebaldism result in?
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ckit mutation results in abnormal TK transmembrane Receptors --> abnormal melanocyte embryogenesis with defecctive melanoblast prolif, migration, and distribution
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Characteristic finding in piebaldism
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white forelock 80-90%
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Inheritance and genes of waardenburg syndrome
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AD; Pax (1 and 3), MITF (2), Sox10 and endothelin (4)
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Pathogenesis of gene causing waardenburg 1 and 3
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PAX3 --> txn factor that controls neural crest differentiation and reg tx of other genes downstream
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Pathogenesis of gene causing waardenburg 2
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MITF --> melanocyte txn factor
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Pathogenesis of gene causing waardenburg 4
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SOX10, endothelin, and endothelin R gene mutations
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T/F patient with waardenburg have depigmented patches
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T
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Hair findings in waardenberg
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Synophry (70%) white forelock (< 50%)
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Nose finding in waardenberg
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Broad nasal root (80%)
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Which waardenburg does not have dystopia canthorum?
WHat is it? |
Not in 2 but in 99%
Lateral displacement of medial canthi with normal interpupillary distance |
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% with heterochromic irides
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25%
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Congenital SNHL is most common in which waardenburg?
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II
about 20% |
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which waardenburg has hirschprung dz?
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< 5%; type IV
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Eponym for hypomelanosis of ito.
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incontinentia pigmenti achromians
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T/F Inheritance of hypomelanosis of ito is AD.
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False - not inherited
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Findings of hypomelanosis of ito
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Marble cake hypopigmentation in blaschkos lines
alopecia CNS - sz Eyes - striabismus and hypertelorism MS - scoliosis and lim length discrepancy Teeth - anodontia |
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Block Sulzberger
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IP
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What is the inheritance and gene of IP?
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XLD; Nemo
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In IP, 97% of survivors are female. What are male survivors thought to have?
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Klinefelter
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What is the function of gene mutated in IP?
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NEMO --> NFkappa beta modulator --> defective activation
of txn factor essential for several inflamm, immune and apoptotic pw |
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Nail, hair and teeth findings....in IP
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Hair - scarring alopecia
Nails - dystrophic changes Teeth - anodontia, peg conical teeth |
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Eye and CNS findings in IP.
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Eye - strabismus, cataracts, optic atrophy, retinal vascular changes
CNS (30%) Sz, MR, spastic pearalysis |
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T/F IP patient have early death.
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False - normal life span
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Inheritance of gene of LEOPARD syndrome
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AD; PTPN11 gene
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Eponym for LEOPARD
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Lentigines - generalize; mucosa spared
ECG conduction defects Ocular hypertelorism Pulmonic stenosis Abonormal Genitalia Retardation of Growth Deafness (SN) |
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Pathogenesis of Leopard
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Defect in PTPN11 --> encodes nonreceptor protein tyrosine phosphatase SHP2 --> implicated in Noonan
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Genoderm implicated by gene defect of Leopard
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PTPN11
Noonan |
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Craniofacial defects in LEOPARD
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ocular hypertelorism
Triangular facies |
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Normal or shortened life span in leopard?
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Normal
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CARNEY Complex Inheritance, eponym, gene
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AD; NAME and LAMB; PRKaR1A
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What does the gene defect in Carney complex cause?
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Tumor suppressor encoding the regulatory subunit type 1A of protein kinase A isolated in half the cases
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NAME =
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Nevi - blue and melanocytic
Atrial myxomas Myxomas Ephelids ( can be on mucosa) |
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Name the endocrine abnormalities found in carney?
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Pigmented nodular adrenocoritical dz - Cushing
Pituitary Adnoma - acromegaly |
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Two other non endocrine tumors seen in Carney.
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Testicular tumors
Psammomatous melanotic schwannomas |
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Treatment of atrial myxomas.
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excision
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Bone findings of mccune-albright syndrome
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polyostotic fibrous dysplasia --. recurrent fx
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Endocrine findings of Mccune albright?
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Precocious purberty;
20-30% hyperthyroidism |
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Eponym for NF1
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Von Recklinghausen Dz
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Inheritance and gene for NF1
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AD; Spontaneous in 50%
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Pathogenesis of NF1
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Neurfibromin is a Tumor suppresor that dampens products of ras proto-oncogenes
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Which is most common form of NF?
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NF1
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For CALMs, number that suggests NF1
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Greater than 6
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Eye findings in NF1
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Lisch nodules - 90% patients > 6 yo; congenital glaucoma
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Skeletal findings of NF1
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Sphenoid wing dysplasia
macrocephaly scoliolsis |
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What is important to check (VS) in NF1 patients?
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Blood pressure --> pheo or RAS
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Dx of NF1 (Consensus)
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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 |
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Inheritance and gene of NF2
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AD; SCH - shwnnomin/merlin protein product --> affects tumor suppressor
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NF and CALM are less or more common in NF2
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Less common
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Eye finding of NF2
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Juvenile posterior subcapsular lenticular opacity
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Characteristic tumor of NF2
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B/l vestibular schwannomas (acoustic schwannoma)
may be complicated by deafness, tinnitus and poor balance |
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Tuberous sclerosis eponym, genes, and inheritance
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Bourneville's syndrome; epiloia
AD TSC1 and TSC2 |
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Products of the TS genes
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TSC1 hamartin, TSC2 tuberin --> tumor suppression and interact to reg GTPas activity
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Most common type of macule?
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Polygonal
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Most characteristic and earliest finding?
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ash leaf macule
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Name the CNS findings in TS.
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Spasms, sz, MR, paraventricular calcification
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Kidney findings of TS
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angiomyolipoma, cysts
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Cardiac TS
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rhabdomyoma
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Findings of lungs in TS
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Lympha\gniomyomatosis
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Any involvement of mouth in TS?
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yes, enamel pits, gingival fibromas
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Another facial finding of TS?
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fibrous plaque of face
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