etas_mcq_03 a genodermatoses
TRANSCRIPT
Genodermatoses1) Tyrosinase positive albinism (oculocutaneous albinism type 2) is caused by a mutation in which of the following:
A. Tyrosinase
B. C-kit
C. NEMO
D. Tyrosinase related protein 1
E. P gene Correct ChoiceOculocutaneous albinism (OCA) type 1 (Tyrosinase negative albinism) is caused by mutations in the tyrosinase gene. OCA type 2 (tyrosinase positive albinism) is caused by mutations in the P gene. OCA type 3 is caused by mutations in the tyrosinase related protein 1 gene. C-kit mutations cause
piebaldism and NEMO mutations cause incontinentia pigmenti.
2) A patient with a port wine stain covering one enlarged leg likely has which of the following associated symptoms?
A. Enchondromas
B. Visceromegaly with omphalocele
C. Distichiasis
D. Lymphatic and deep venous insufficiency Correct Choice
E. Bilateral retinal hemangioblastomas
Klippel-Trenaunay-Weber syndrome is a sporadic condition characterized by port-wine stains typically covering one lower extremity that is enlarged with underlying lymphatic and deep venous insufficiency.
3) Patients with Hermansky-Pudlak syndrome may experience which of the following systemic complications as a result of their disease?
A. Aortic stenosis
B. Rectal abscesses
C. Arteriovenous malformations
D. Gastroesophageal reflux disease
E. Pulmomary fibrosisCorrect Choice
Patients with Hermansky-Pudlak syndrome are tyrosinase positive albinos. In addition to their pigmentary dilution and increased risks for cutaneous malignancies, patients lack platelet granules leading to impaired platelet aggregation (and therefore a bleeding diathesis). There is also a lysosomal membrane defect which leads to the accumulation of ceroid lipofuscion in macrophages
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within the lung (leading to pulmonary fibrosis), gastrointestinal tract (leading to granulomatous colitis), and heart (cardiomyopathy).
4) Non-bullous icthyosiform erythroderma is caused by which of the following mutations
A. 12R-lipoxygenase gene (ALOX12B)
B. lipoxygenase-3 gene (ALOXE3)
C. All of these answers are correctCorrect Choice
D. transglutaminase-1 gene (TGM1)
E. Both 12R-lipoxygenase gene (ALOX12B) and lipoxygenase-3 gene (ALOXE3) are correct
Non-bullous congenital erythroderma (NCIE)is an autosomal recessive disorder characterized by a collodion baby presentation at birth, and generalized erythroderma with fine white scale, palmoplantar keratoderma, and heat intolerance. NCIE may be caused by mutations in transglutaminase-1 gene (TGM1), the 12R-lipoxygenase gene (ALOX12B), and the lipoxygenase-3 gene (ALOXE3). Mutations in the keratinocyte TGM1 gene interferes with normal cross-linking of structural proteins and the lipid envelope, leading to defective cornification and desquamation.ALOXE3 functions as an epoxy alcohol synthase using the product of ALOX12B as the preferred substrate; either gene can be the site of mutations causing NCIE.
5) In which of the following Genodermatoses would one find cutaneous hyperpigmentation, blue lunulae and Kayser-Fleishcher rings
A. Hemochromatosis
B. Osteogenesis Imperfecta
C. Marfan's Disease
D. Gaucher's Disease
E. Wilson's DiseaseCorrect Choice
In Wilson's disease (Hepatolenticular Degeneration) one will find a vague greenish discoloration of the skin on the face, neck, and gentalia Hyperpigmentation), azure lunulae (sky-blue moons) of the nails, and Kayser-Fleischer rings. This is due to the body retaining excessive amounts of copper
6) Christ-Siemens-Touraine Syndrome is most commonly linked with defects in which of the following genes?
A. ectodysplasin (EDA)Correct Choice
B. ERCC2
C. NEMO
D. None of these options are correct
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E. ATP7A
Ectodysplasin (EDA) on Xq12-q13 is transmitted in an X-linked recessive fashion and is the most common cause of anhidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome or hypohidrotic ectodermal dysplasia). NEMO can be linked to this syndrome and is associated with immunodeficiency, but this is a rare association. ERCC2 is associated with trichothiodystrophy and ATP7A with Menkes kinky hair syndrome. They are not associated with anhidrotic ectodermal dysplasia.
7) Cronkhite-Canada is associated with gastrointestinal polyposis, nail atrophy, alopecia, generalized pigmentation of skin and melanotic macules on the fingers. Which of the following describes its inheritance pattern?
A. X-linked dominant
B. X-linked recessive
C. Autosomal recessive
D. Autosomal dominant
E. SporadicCorrect Choice
Cronkhite-Canada is associated with gastrointestinal polyposis, nail atrophy, alopecia, generalized pigmentation of skin and melanotic macules on the fingers. It is inherited in a sporadic manner.
8) A biopsy is taken from a patient with multiple facial lesions is shown. They also have oral papillomas and acral keratotic papules. Which of the following genes is most likely involved in the etiology of these lesions?
A. CDKN2A
B. PTENCorrect Choice
C. NCF1
D. NCF2
E. CYBA
The biopsy shown is a trichilemmoma. Patients with Cowden syndrome (multiple hamartoma syndrome) will have multiple facial trichilemmomas in addition to the other findings mentioned. Also present are multiple other adenomas and potentially adenocarcinomas, especially of the thyroid and breast. Hamartomatous polyps of the gastrointestinal tract are also present.
The other listed genes are not involved in Cowden syndrome. CYBA, NCF1/2 are involved in chroinc granulomatous disease and CDKN2A is associated with familial dysplastic nevi.
9) Ectopia lentis (downward displacement of the lens) is characteristic of:
A. Multiple Carboxylase deficiency
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B. HomocystinuriaCorrect Choice
C. Ehlers-Danlos syndrome
D. Phenylketonuria
E. Marfan syndrome
Ectopia lentis (downward displacement) is seen in homocystinuria. Upward displacement is seen in Marfan syndrome. There are no changes in the lens in phenylketonuria or multiple carboxylase deficiency
10) An infant presents with multiple congenital hemangomas in an generalized distribution. What is the most serious associated condition?
A. None of the answers are correct
B. All of the answers are correct
C. Obstructive jaundice
D. Congestive Heart FailureCorrect Choice
E. Portal hypertension
High output congestive heart failure can lead to death in these children. Obstructive jaundice and portal hypertension both occur, but are less likely to cause death. The hemangiomas will undergo spontaneous regression.
11) What medication may exacerbate this autosomally dominant, acnatholytic disorder?
A. LithiumCorrect Choice
B. Oral contraceptives
C. Phenytoin
D. Corticosteroids
E. Anti-malarials
Darier's disease is autosomal dominant condition characterized by hyperkeratotic papules coalescing into warty plaques and cobblestoned papules on mucosal surfaces. The cutaneous manifestations may be exacerbated by lithium.
12) Which of the following subtypes of Ehlers-Danlos Syndrome (EDS) is associated with early demise?
A. Type 4 (Vascular) Correct Choice
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B. Type 5 (X-linked)
C. Type 1 (Gravis)
D. Type 7 (Arthrochalasis multiplex congenita)
E. Type 10 (Fibronectin)
Ehlers-Danlos Syndrome type 4 (Vascular) is caused by mutations in collagen 3 in some cases. There is a tendency to develop arterial and visceral rupture resulting in early death.
13) An infant presents with poikiloderma on his face, buttocks, arms and legs. He is also noted to have a hypoplastic thumb and no radius. Yearly ophthalmologic examination is indicated because of the infant is at risk for developing:
A. Subcapsular lens displacement
B. Macular degeneration
C. Glaucoma
D. Copper deposition
E. CataractsCorrect Choice
The patient described has Rothmund-Thomson syndrome (or poikiloderma congentiale), an autosomal recessive disease localized to chromosome 8 and believed to be due to a DNA helicase mutation (RECQL4). 40-50% of patients will develop juvenile cataracts before puberty. Other clinical features include alopecia, dystrophic nails, short stature, hypogonadism and dental dysplasia.
14) Retention of primary teeth a dental finding of which of the following conditions?
A. Letterer-Siwe disease
B. Tuberous sclerosis
C. Hypomelanosis of Ito
D. Hyper-IgE syndrome Correct Choice
E. Jackson Sertoli syndrome
Hyper-Immunoglobulin E syndrome is an autosomal dominant condition with impaired regulation of IgE function and deficient neutrophil chemotaxis. There is increased susceptibilty to infections and increased IgE serum levels. Retained primary teeth and lack of development of secondary teeth are characteristic findings. The remaining conditions do not have this as a prominent finding.
15) A patient with a white, spongy overgrowth of the buccal mucosa that has passed in an autosomal dominant fashion is most likely related to a mutation in which of the following?
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A. Keratin 6b/17
B. Keratin 1/10
C. Keratin 6a/16
D. None of these options are correct
E. Keratin 4/13Correct Choice
This description is most likely a white sponge nevus, an autosomal dominant defect in keratin 4/13. Keratin 1/10 is mutated in epidermolytic hyperkeratosis and Unna-Thost PPK, Keratin 6a/16 in pachyonychia congenita type I, and keratin 6b/17 in pachyonychia congenita type II.
16) Dental enamel pits are seen in which of the following conditions?
A. Hypomelanosis of Ito
B. Tuberous sclerosisCorrect Choice
C. Hyper-IgE syndrome
D. Letterer-Siwe disease
E. Jackson Sertoli syndrome
Tuberous sclerosis is an autosomal dominant condition caused by mutations of the TSC1 (hamartin) or TSC2 (tuberin) genes. These are tumor suppressor genes. Skin findings include hypopigmented macules, connective tissue nevus, facial angiofibromas, periungual fibromas and cafe au lait macules. Dental enamel pits and gingival fibromas are oral findings that are associated with this condition. The remaining conditions do not have dental pits.
17) A 4-year old boy presents with generalized white scale. The mother reports that her son was born with a tight membrane enveloping his body. Peripheral blood smear is within normal limits. What is the most likely diagnosis?
A. ichthyosis vulgaris
B. lamellar ichthyosis
C. neutral lipid storage disease
D. netherton syndrome
E. Congenital ichthyosiform erythrodermaCorrect Choice
The most likely diagnosis is Congenital ichthyosiform erythroderma. In neutral lipid storage disease, the peropheral blood smear would demonstrate lipid vacuoles in leukocytes and monocytes. Lamellar ichthyosis is characterized by plate-like scale in children/adults. Netherton syndrome is characterized by ichthyosis linearis circumflexa. Ichthyosis vulgaris does not typically present with collodian baby
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18) Mosaic mutations in PTEN are seen in which of the following conditions?
A. Gardner syndrome
B. Noonan syndrome
C. Incontinentia pigmenti
D. Proteus syndrome Correct Choice
E. Beckwith-Wiederman syndrome
Proteus syndrome is a sporadic condition caused by postzygotic mosaic mutations in PTEN. Clinical features include subcutaneous lymphovenous malformations, capillary malformations, lipomas, connective tissue nevi of palms/soles, hemihypertrophy, frontal bossing, hyperostoses of epiphyses & skull (especially external auditory canal), scoliosis, bilateral ovarian cystadenomas, and parotid monomorphic adenomas.
19) Which syndrome is characterized by hyperhidrosis, lack of pain sensation, hypersalivation, and absent fungiform papillae?
A. Rubinstein-Taybi syndrome
B. Noonan Syndrome
C. Turner Syndrome
D. Riley-Day Correct Choice
E. Cornelia de lange Syndrome
Riley-Day syndrome is also known as Familial Dysautonomia. It is an autosomal recessive disorder with the gene defect on the long arm of chromosome 9. Patients have unmyelinated sensory and sympathetic neurons and autonomic dysfunction, leading to hyperhidrosis, decreased corneal sensation and tear flow, hypersalivation, gastroesophageal reflux, decreased deep tendon reflexes, and lack of pain sensation. They also exhibit abnormal histamine skin test.
20) Homocystinuria is caused by a defect in:
A. holocarboxylase synthetase
B. biotinidase
C. phenylalanine hydroxylase
D. cystathione beta-synthetaseCorrect Choice
E. gp91-phox
Cystathione beta-synthetase is defective in homocystinuria, an autosomal recessive conditions characterized by increased homocystine and methionine levels in blood and urine. Other findings
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include a malar flush, DVTs/emboli, cardiovascular disease, livedo reticularis, leg ulcers, blonde hair/fiar complexion, downward lens dislocation, glaucoma, mental retardation, seizures, psychiatric disorders and a marfanoid body habitus. The other enzymes are not involved in this condition.
21)Hypoplasia of the breast can be seen in which disease?
A. anhidrotic ectodermal dysplasiaCorrect Choice
B. osteogenesis imperfecta
C. congenital syphilis
D. Marfan syndrome
E. Maffucci syndrome
Anhidrotic ectodermal dysplasia is a X-linked recessive disease caused by mutations in ectodysplasin, a member of the tumor necrosis family. Patients may have dry skin with pigmentation periorbitally, hypohidrosis, sparse hair, hypo-anodontia, nail dystrophy, and frontal bossing, and saddle nose deformity. In addition to abnormalities of other ectodermally derived structures, the breast and nipple-areolar complex may be absent or hypoplastic.
22) Which radiologic finding is associated in Fanconi's anemia?
A. posterior iliac horns
B. absent radiiCorrect Choice
C. osteopoikilosis
D. absent thumb
E. osteopathia striata
Fanconi's anemia is an inherited disease that primarily affects the bone marrow, resulting in pancytopenia. It is also associated with a broad variety of physical anomalies. Cutaneous findings include cafe-au-lait macules and vitiligo.
23) Birt-Hogg-Dube syndrome is most strongly associated with which of the following malignancies?
A. Renal cell carcinoma Correct Choice
B. Eccrine syringofibroadenoma
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C. Trichoepithelial carcinoma
D. Medulloblastoma
E. Basal cell carcinoma
Birt-Hogg-Dube syndrome is characterized by multiple fibrofolliculomas, trichodiscomas, acro-collagenomas, lipomas, and oral fibromas. Patients develop renal cell carcinoma, colon cancer, and medullary thyroid carcinoma.
24) A seven month old infant diagnosed with eczema on her face returns for a diaper-rash follow-up. A one-month trial of topical antifungals has failed to improve the infant’s systems. The part of the physical exam that might prove most useful include:
A. Hearing test
B. Palpation of abdomen
C. Examination of palms and solesCorrect Choice
D. Stool samples
E. Fontanelle examination
Acrodermatitis enteropathica presents itself in infancy once breastfeeding has stopped. It can clinically mimic atopic dermatitis, seborrheic dermatitis and candidiasis. Clinical features include scaly red rash around mouth, eyes, and palms, diarrhea, stomatitis, glossitis, alopecia, and failure to thrive.
25) What is the inheritance pattern of chronic granulomatous disease?
A. Autosomal dominant
B. Sporadic
C. X-linked recessiveCorrect Choice
D. X-linked dominant
E. Autosomal recessive
Chronic granulomatous disease is inherited in an x-linked recessive manner. There are mutations present in CYBA (a cytochrome subunit), CYBB, and NCF1 & 2 (neutrophil cytosol factors 1 & 2).
26) Epidermolysis bullosa simplex is caused by blistering in which structure?
A. Spinous layer keratinocyte
B. Granular layer keratinocyte
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C. Basal layer keratinocyte Correct Choice
D. Sublamina densa
E. Lamina densa
Epidermolysis bullosa simplex is caused by mutations in keratin 5 and 14 resulting in bullae within basal cell keratinocytes.
27) Hyperextesible skin, gaping wounds, cigarette-paper scars, molluscoid pseudotumors, and calcified subcutaneous nodules are characteristic of which syndrome?
A. Marfan syndrome
B. Congenital contractural arachnodactyly
C. Ehlers-Danlos Syndrome Correct Choice
D. Cutis laxa
E. Pseudoxanthoma elasticum
The most common type of EDS is EDS type I (gravis). Cutaneous features include hyperextensible skin, gaping wounds, cigarette-paper scars, molluscoid pseudotumors, calcified subcutaneous nodules, and bruises. Systemic features include hypermobile joints with dislocation, hernias, mitral valve prolapse, blue sclerae, Gorlin’s sign (tongue reaches nose), and absence of the lingual frenulum
28) Lamellar ichthyosis is caused by mutations in which of the following genes?
A. Phytanoyl coenzyme A hydroxylase deficiency
B. Arylsulfatase E
C. Steroid sulfatase
D. Transglutaminase Correct Choice
E. Fatty aldehyde oxidoreductase
Nonbullous congenital ichthyosiform erythroderma and lamellar ichthyosis are caused by mutations in the transglutaminase gene.
29) The coast of Maine cafe au lait macule is a common finding in which of the following syndromes?
A. Russell-Silver syndrome
B. McCune-Albright syndromeCorrect Choice
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C. Watson syndrome
D. Tuberous Sclerosis
E. Neurofibromatosis type I
McCune-Albright syndrome is due to a sporadic somatic mutation in Gs subunit of adenylate cyclase. The "coast of Maine" cafe au lait macule is a characteristic finding. Other findings in clude polyostotic fibrous dysplasia and precocious puberty. Tuberous sclerosis, Neurofibromatosis type I, Watson syndrome (pulmonic stenosis and CALM's) and Russell-Silver syndrome (CALMs, short stature, precocious puberty, cryptorchidism and musculoskeletal/craniofacial defects) all have CALMs as a feature, but not the jagged type seen in McCune-Albright syndrome.
30) Enchondromas and chondrosarcomas are most strongly associated with which of the following syndromes?
A. Nonne-Milroy disease
B. Blue rubber bleb nevus syndrome
C. Maffucci syndrome Correct Choice
D. Osler-Weber-Rendu syndrome
E. Proteus syndrome
Maffucci syndrome is a sporadic condition caused by defects in the parathyroid hormone/parathyroid hormone related protein type 1 receptor. There are venous malformations of distal extremities, and benign enchondromas that can degenerate into chondrosarcomas.
31) Epistaxis in early childhood to teens followed by multiple cutaneous and gastrointestinal telangectasias describes which of the following syndromes?
A. CREST syndrome
B. Maffucci syndrome
C. Hereditary Hemorrhagic Telangiectasia syndromeCorrect Choice
D. Ataxia telangectasia
E. Fabry disease
Hereditary Hemorrhagic Telangiectasia syndrome is described above. The first signs in over 50% of cases is epistaxis in childhood to young adulthood. Telangectiasias develop in the 30's and 40's. Other findings include gastrointestinal telangiectasia, hepatic and pulmonary arteriovenous malformations. The other syndromes listed can have cutaneous vascular lesions and should be considered on the differential for hereditary hemorrhagic telangiectasia syndrome
32) Which syndrome is characterized by broad thumbs, a large beaked nose, and capillary malformation?
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A. Rubinstein-TaybiCorrect Choice
B. Bloom syndrome
C. Proteus syndrome
D. Ehlers-Danlos syndrome
E. Klinefelter
Rubinstein-Taybi syndrome has been associated with a deletion localized to the short arm of chromosome 16. Patients are severely retarded with strabismus, crytorchidism, and congenital heart defects. They have a characteristic beaked nose with nasal septum below alae accompanied by a broad nasal bridge, downslanting palpebral fissures, and broad thumbs and halluces.
33) Which of the following immunoglobulins is commonly decreased in Wiskott-Aldrich syndrome?
A. IgE
B. IgG
C. IgA
D. IgMCorrect Choice
E. IgD
IgM is decreased in WAS. IgA, IgD and IgE levels are all elevated. IgG is not abnormal in WAS.
34) Mutations affecting the VEGF receptor-3 cause which of the following disorders?
A. Lymphedema-distichiasis syndrome
B. Noonan syndrome
C. Lymphedema and ptosis
D. Hereditary hemorrhagic telangiectasias
E. Hereditary lymphedema (Nonne-Milroy disease) Correct Choice
Hereditary lymphedema (Nonne-Milroy disease) is an autosomal dominant condition caused by mutations in the FLT4 gene which encodes for VEGF receptor-3. There is congenital lymphedema and chylous ascites, scrotal swelling, intestinal tract protein loss, persistent bilateral pleural effusion, and hypoproteinemia
35) What is a possible gene defect in this patient with a white forelock?
A. tyrosinase
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B. c-kitCorrect Choice
C. P gene
D. tyrosinase-related protein 1
E. PAX3
Piebaldism is an autosomal dominant condition caused by a mutation in c-kit which is a mast and stem cell growth factor. This mutation leads to defective melanoblast proliferation and depigmented pathces on the trunk and white forelock. Other features include Hirschprung disease, mental retardation, deafness and cerebellar ataxia.
36) Beare-Stevenson cutis gyrata syndrome is linked with mutations in:
A. ATP7A
B. BSCL2
C. None of these answers are correct
D. Fibroblast growth factor receptor 2Correct Choice
E. LMNA
Beare-Stevenson cutis gyrata syndrome has been linked to mutations in fibroblast growth factor receptor 2. This syndrome is characterized by: craniosynostosis, ciutis gyrata, acanthosis nigricans, anogenital anomalies, skin tags, prominent umbilical stump, furrowed palms and soles. Apert syndrome is also linked to this mutation. BSCL2 is linked to Berardinelli-Seip congenital lipodystrophy, LMNA to Familial partial lipodystrophy and ATP7A to Menkes kinky hair syndrome.
37) Which of the following medications is a teratogen associated with a aplasia cutis congenita?
A. Methimazole Correct Choice
B. Alcohol
C. Lithium
D. Warfarin
E. Propranolol
Aplasia cutis congenita is characterized by well-demarcated erosions at birth that heal with atrophic, alopecic scars. Some cases are caused by medications, with methimazole considered a teratogen particularly associated with this condition.
38) A patient with Cowden syndrome presents with a history of breast carcinoma. What other carcinoma should she be examined/screened for?
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A. Uterine
B. ThyroidCorrect Choice
C. Ovarian
D. Bone
E. Colon
Patients with Cowden syndrome are at increase risk for thyroid and breast adenocarcinomas. Ovarian, uterine, colon and bone cancer risks are not elevated in this syndrome.
39) Which ocular finding may be seen in a patient with this skin condition?
A. comma-shaped corneal opacities
B. congenital hypertrophy of the retinal pigmented epithelium
C. retinitis pigmentosa
D. angioid streaksCorrect Choice
E. pingueculae
Pseudoxanthoma elasticum is caused by a defect in connective tissue. Angioid streaks develop when a rupture occurs in Bruch;s membrane.
40) Which of the following elastic tissue diseases demonstrates calcified elastic fibers?
A. Pseudoxanthoma elasticumCorrect Choice
B. Cutis laxa
C. Buschke-ollendorf syndrome
D. Marfan syndrome
E. Anetoderma
Pseudoxanthoma elasticum is usually an autosomally recessive inherited condition due to a defective transport protein, ABCC6. The clinical manifestations of the disease arise from fragmented and calcified fibers of the skin, eyes and arteries. Patients may have yellow papules, loose redundant skin, angioid streaks and hemorrhage. Histologically, the hallmark of pseudoxanthoma elasticum is calcified elastic fibers.
41) Junctional epidermolysis bullosa with pyloric atresia is associated with mutations in:
A. Laminin 5
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B. The alpha-6 subunit of integrin
C. The beta-4 subunit of integrin
D. Plectin
E. Both subunits of integrin can have mutations causing this type of junctional epidermolysis bullosaCorrect Choice
Both subunits of integrin can have mutations causing this type of junctional epidermolysis bullosa. Plectin is associated with epidermolysis bullosa simplex with muscular dystrophy. Laminin 5 is mutated in Herlitz and non-Herlitz types of junctional epidermolysis bullosa.
42) Which of the following condition is NOT found in Von-Hippel Lindau syndrome?
A. Pheochromocytoma
B. Bilateral retinal hemangioblastomas
C. Renal cell carcinoma
D. Connective tissue neviCorrect Choice
E. Cerebellar/CNS hemangioblastomas
Von Hippel-Lindau syndrome is characterized by all the options listed except connective tissue nevi. Other findings include pancreatic cysts/carcinoma and cutaneous capillary malformations of the head and neck and polycythemia.
43) Which syndrome is due to a defective secreted mammilian Ly6/uPAR-related protein-1?
A. Netherton's syndrome
B. Mal de Meleda syndromeCorrect Choice
C. Refsum's syndrome
D. Haim-Munk syndrome
E. Sjogren-Larsson syndrome
Mal de Meleda, also known as keratoderma palmoplantaris transgrediens, is due to a defect in secreted mammilian Ly6/uPAR-related protein or SLURP-1.
44) You are examining a child with mild albinism, immunodeficiency and silver grey highlights in his hair. You diagnose the child with Chediak-Higashi syndrome. Why are you confident that this isn’t Griscelli syndrome?
A. Griscelli syndrome has no changes in hair color
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B. None of these answers are correct
C. All of these answers are correct
D. Griscelli syndrome does not have albinism as a feature
E. Giant lysosomal granules are present in neutrophils in the blood smearCorrect Choice
Chediak-Higashi syndrome and Griscelli syndrome have similar features including silver-grey highlights of hair, immunodeficiency, mild albinism and an accelerated phase of disease. Examining a peripheral blood smear is helpful in distinguishing between these two syndromes. Patients with the LYST defect (a lysosomal storage transport gene) have Chediak-Higashi syndrome and will have giant lysosomal granules visible in white blood cells on a blood smear
45) Adenosine deaminase deficiency is seen in which immunodeficient disease?
A. Wiskott-Aldrich syndrome
B. Chronic granulomatous disease
C. Leiner’s disease
D. Job syndrome
E. Severe combined immunodeficiency syndromeCorrect Choice
Severe combined immunodeficiency is a heterogeneous group of disorders characterized by decreased humoral and cell mediated immunity. Patients may have recurrent infections including cutaneous ones, GVHD (due to in utero cmaternal lymphocytes), sepsis, oral candidiasis, and diarrhea. Implicated genes include the IL-2 receptor (x-linked recessive form) and adenosine deaminase deficiency (autosomal recessive form).
46) Dystrophic epidermolysis bullosa is associated with mutations in collagen VII. Trauma or friction induced blistering in these patients have a plane a splitting in the:
A. Stratum spinosum
B. None of these answers are correct
C. Sublamina densaCorrect Choice
D. Stratum basale
E. Lamina lucida
The split in dystrophic epidermolysis bullosa is found in the sublamina densa, where the collagen VII anchors the epidermis to the anchoring plaques in the dermis. The remaining options are incorrect
47) What is the most likely nail findings in a patient who has this autosomal dominant disease with these keratotic papules and cobblestoning of the oral mucosa?
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A. Red and white longitudinal bandsCorrect Choice
B. Koilonychia
C. Pincer nails
D. Melanonychia
E. Half and half nails
Darier's disease is an autosomal dominant disorder characterized by greasy hyperkeratotic papules. The papules often coalesce into a warty plaque and have a tendency for secondary viral or bacterial infection. The mutation is in calcium ATPase 2A2. The classic nail finding is red and white longitudinal bands with V-shaped nicking.
48) Low-cystine content in hair and nails may contribute to the phenotype seen in:
A. Wilson’s disease
B. Bjornstad
C. Tay SyndromeCorrect Choice
D. Menke’s Kinky Hair syndrome
E. Nethertons
Tay Syndrome is also known as trichothiodystrophy, or (P)IBIDS: (photosensitivity), icthyosis, brittle hair, intellectual impairment, decreased fertility, and short stature. Hair shaft has a characteristic “tiger tail” appearance under polarized light and the low cystine content in hair and mails is thought to be responsible for the phenotype seen.
49) Bilateral ovarian cystadenomas and parotid monomorphic adenomas are seen in which of the following conditions?
A. Beckwith-Wiederman syndrome
B. Von-Hippel-Lindau syndrome
C. Proteus syndrome Correct Choice
D. Cowden syndrome
E. Noonan syndrome
Proteus syndrome is a sporadic condition caused by postzygotic mosaic mutations in PTEN. Clinical features include subcutaneous lymphovenous malformations, capillary malformations, lipomas, connective tissue nevi of palms/soles, hemihypertrophy, frontal bossing, hyperostoses of epiphyses and skull (esp. external auditory canal), scoliosis, bilateral ovarian cystadenomas, and parotid monomorphic adenomas.
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50) Maffucci syndrome is has characteristic venous malformations of the distal extremities and benign endochondromas which can compromise bone strength and lead to chondrosarcomas. The defect causing this believed to be the PTH/PTHrP type I receptor which is inherited in which manner?
A. Autosomal recessive
B. X-linked recessive
C. X-linked dominant
D. Autosomal dominant
E. SporadicCorrect Choice
Maffucci syndrome is inherited in a sporadic manner
51) What phenotype results from a low activity of double stranded RNA adenosine deaminase?
A. oculocutaneous albinism type 4
B. Piebaldism
C. Waardenberg's syndrome type 2
D. Tietz syndrome
E. dyschromatosis symmetrica hereditariaCorrect Choice
Dyschromatosis symmetrica hereditaria (or acropigmentation symmetrica of Dohi) is an autosomal dominant disease with hypo and hyper pigmented macules and patches on the dorsal hands and feet associated with a low activity of double stranded RNA adenosine deaminase
52) Which of the following is not classically associated with pheochromoctyoma?
A. Multiple Endocrine Neoplasia Type IIA
B. Neurofibromatosis
C. Multiple Endocrine Neoplasia Type IIB
D. Cobb SyndromeCorrect Choice
E. Von-Hippel-Lindau Syndrome
Cobb syndrome is a sporadic disease characterized by cutaneous vascular malformations associated with malformations of the spinal cod.
53) A 17 y/o man presents with facial acne that he would like treated. You notice that he has fine brown scale on his neck and do a complete skin exam. This scale is present on the remainder of his body, sparing his palms, soles and flexural areas. He informs you that his uncles on his mother’s side have similar skin findings. He is not concerned about the skin and would like to proceed with
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acne treatment only. What other clinical exam should you perform to screen for a potential malignancy to which this patient is at higher risk for acquiring?
A. Lung
B. Rectal
C. Abdominal
D. TesticularCorrect Choice
E. Lymph node
Men with x-linked ichthyosis are at increased risk of testicular cancer and cryptorchidism. A testicular exam is simple to perform and a good screening exam for detecting testicular abnormalities. The remaining exams are not useful as these patients are not at higher risk for other types of cancer
54) Naxos syndrome is characterized by a right sided cardiomyopathy, wooly hair, and keratoderma. The epidermal structure defective in Naxos syndrome is:
A. desmoplakin
B. plakoglobinCorrect Choice
C. desmoglein 3
D. desmoglein 1
E. Keratin 1/10
Plakoglobin is an intracellular desmosomal component which binds desmogleins/desmocollins on one side and to desmoplakin on the other. Desmoplakin in turn binds to the keratin intermediate filaments, K1/10 in most cases. Mutation of desmoplakin leads to CarvajaL syndrome, which is associated with a striate palmoplantar keratoderma, woolly hair and Left sided cardiomyopathy. A simple way to remember this is the L in Carvajal cooresponds to the Left sided cardiomyopathy vs. the right sided disease in Naxos disease.
55) What cutaneous manifestation is associated with familial cerebral cavernomas?
A. hyperkeratotic cutaneous capillary-venous malformations(HCCVM)Correct Choice
B. Verrucous hemangioms
C. segmental facial hemangiomas
D. Tufted angiomas
E. Glomeruloid hemangiomas
Familial cerebral cavernomas are due to a defect in the CCM gene which encodes the KRIT-1 protein. These patients often times have hyperkeratotic cutaneous capillary-venous malformations.
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56) "Mousy" odor of urine is characteristic of which of the following syndromes?
A. Maple Syrup Urine disease
B. Hunter disease
C. Alkaptonuria
D. Hurler disease
E. PhenylketonuriaCorrect Choice
Phenylketonuria will cause a "mousy" odor in the urine. Patients with Alkaptonuria will have black urine. Maple syrup urine disease will have a sweet odor. Hunter/Hurler diseases are not associated with urinary issues.
57) Which disease can clinically mimic pellagra but is inherited in an autosomal recessive fashion and is due to a defect in the transport of neutral amino acids?
A. Fabry
B. Wilsons
C. Gaucher’s
D. Hartnup DiseaseCorrect Choice
E. Hemochromatosis
The clinical manifestation of Hartnup disease is similar to that of pellagra because the resultant defect in the transport of amino acids leads to low levels of tryptophan. Since tryptophan is required to make nicotinic acid, pts with Hartnup disease manifest the same symptoms as niacin-deficient patients (pellagra).
58) A child presents with the hair finding seen in the image in addition to brittle nails, keratosis pilaris, abnormal teeth and cataracts. Which of the following abnormalities is the most likely mutated?
A. Keratin hHb1/hHb6Correct Choice
B. Keratin 1/10
C. Keratin 2e
D. Keratin 6/17
E. Keratin 6/16
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Keratin hHb1/hHb6 is defective in monilethrix, which is described above. Keratin 1/10 defects are found in epidermolytic hyperkeratosis, K6/16 in inflamed skin and pachyonychia congenita type I, K6/17 in pachyonychia congenita type II and K2e in Ichythosis bullosa of Siemens
59) Which malignancy is associated with Cowden syndrome?
A. Colon cancerCorrect Choice
B. Renal cancer
C. Lung cancer
D. Basal cell cancer
E. Ovarian cancer
Cowden syndrome is a autosomal dominant syndome with tricholemmomas, oral mucosal papules, acral keratotic papules, thyroid goiter, GI polyps, and fibrocystic breast disease. Malignant associations include breast, thyroid follicular carcinoma, and colon adenocarcinoma.
60) The combination of gastrointestinal polyposis, nail atrophy, alopecia, generalized pigmentation of skin, and melanotic macules of the fingers is characteristic of which of the following syndromes?
A. Cronkhite-Canada syndrome Correct Choice
B. Bannayan-Riley-Ruvalcaba syndrome
C. Cowden syndrome
D. Nicolau-Balus syndrome
E. Peutz-Jeghers syndrome
Cronkhite-Canada syndrome is a sporadic gastrointestinal polyposis syndrome associated with nail atrophy, alopecia, generalized pigmentation of the skin, and melanotic macules on the fingers.
61) Which of the following syndromes is associated with cutis marmorata?
A. Netherton’s
B. Cornelia de Lange syndromeCorrect Choice
C. Hemansky-Pudlak syndrome
D. Maffucci syndrome
E. Papillon-Lefevre syndrome
Cornelia de Lange is also known as Brachmann-de Lange syndrome. Cutaneous manifestations include cutis marmorata, hirsutism, hypoplastic nipples and umbilicus. Patients also have small
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hands and feet. They have characteristic facies which include hirsutism on the forehead, trichomegaly, synophrys, anteverted nostrils, long philtrum, and low-set ears.
62) Lamellar ichthyosis is caused by a defect in transglutaminase 1. It can present as a colloidion baby at birth with subsequent large thick plates of scale especially on flexures, ectropion and eclabium. If two unaffected carrier parents have a child, how likely is their child to have this condition?
A. Only male offspring are affected
B. None of these answers are correct
C. Only female offspring are affected
D. 25%Correct Choice
E. 75%
Lamellar ichthyosis is an autosomal recessive condition. If each parent is a heterozygous carrier, there is a 25% chance that the child will be affected, 50% chance that the child will be a heterozygous carrier and a 25% chance that the child will not be a carrier or affected with lamellar ichthyosis.
63) A 18 yo man presents for evaluation of foot lesions. There are thick hyperkeratotic plaques symmetrically on only the weight bearing plantar surfaces. What test(s) should this patient be referred for?
A. Thoracic CT
B. Head CT
C. EndoscopyCorrect Choice
D. Hepatic ultrasound
E. Knee films
The patient likley has Howel-Evans Syndrome. These patients present with symmetric focal weight bearing PPK in the second decade to adulthood. After the third decade, esophageal carcinoma can occur. These patients should have periodic endoscopic evaluation.
64) To help diagnose trichothiodystrophy, which of the following levels are decreased in hairs of affected individuals?
A. Histidine
B. Arginine
C. CysteineCorrect Choice
D. Glycine
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E. Phenylalanine
Cysteine and Methionine levels are decreased in hair and nails of patients with trichothiodystrophy. Other sulfur containing amino acids include: Gluthathione, Taurine, and Homocysteine. Testing hairs for decreased sulfur content is an indirect method of determining this. The other listed amino acids are present in normal levels in the hair and nails of trichothiodystrophy patients
65) Adenosine deaminase deficiency is associated with which of the following disorders?
A. Xeroderma pigmentosum
B. Wiskott Aldrich syndrome
C. Gout
D. Severe combined immunodeficiencyCorrect Choice
E. Job syndrome
Adenosine deaminase deficiency is associated with severe combined immunodeficiency. The most common inheritance is x-linked recessive. It is a mixed group of disorders all sharing defects in cell-mediated and humoral immunity. Skin findings include: candidal infections, mucocutaneous, bacterial pyodermas, seborrheic-like dermatitis/lichen planus-like sclerodermatous changes, aplastic thymus and pneumonias. The other listed syndromes are not associated with adenosine deaminase deficiency.
66) Which eye findings would be expected in an individual with this disorder associated with atherosclerosis?
A. dendritic corneal ulcerations
B. salt and pepper retinitis pigmentosa
C. angoid streaksCorrect Choice
D. keratoconus
E. ectopia lentis
Pseudoxanthoma elasticum is an autosomal rescessive or autosomal domminant disease caused by a mutation in ABCC6 (adenosine triphosphate-binding cassette subfamily C member 6). Associated findings include gastric artery hemorrhage, angiod streaks, retinal hemorrhage, atherosclerotic disease, and a possible increased risk of first trimester miscarriage.
67) Which of the following is caused by a mutation in a gene which codes for steroid sulfatase?
A. Lamellar icthyosis
B. Chediak-Higashi
C. X-linked ichthyosisCorrect Choice
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D. Lesch-nyhan disease
E. Fabry disease
The mutation in X-linked icthyosis is found in the gene for aryl sulfatase C, a steroid sulfatase. The genetic defect in Fabry disease occurs in alpha-galactosidase A (which hydrolyzes glycolipids and glycoproteins), the defect in lamellar icthyosis codes for transglutaminase 1 and the defect in chediak higashi occurs in a lysosomal transport protein.
68) Meleda is an island off the coast of Croatia. Its inhabitants have an increased frequency of a malodorous transgradiens palmoplantar keratoderma in a stocking-glove distribution. This condition is autosomal recessive with a defect in:
A. Cathepsin C
B. Keratin 1/9
C. SLURP1 geneCorrect Choice
D. TOC gene
E. Loricrin
SLURP1 (Secreted LY6/UPAR-related protein 1) is defective in Mal de Meleda. Keratin 1/9 are defective in Unna-Vorner/Thost palmoplantar keratoderma, an AD diffuse symmetric non-transgradiens PPK. TOC gene is defective in Howel-Evans syndrome, an AD PPK associated with focal, pressure-related, non-transgradiens PPK and esophageal cancer/oral leukoplakia. Loricrin mutations are seen in Vohwinkel syndrome variant and symmetric progressive erythrokeratodermia. Cathepsin C defects are seen in Haim-Munk syndrome (PPK+periodontitis+acroosteolysis+onychogryphosis) and Papillon-Lefevre syndrome (sharply demarcated transgradiens, stocking-glove PPK+periodontitis+dural calcifications and choroids attachments)
69) A patient with thyroid carcinoma and cobblestone-like changes of the oral mucosa will also likely have:
A. Syringomas
B. Cylindromas
C. Trichoepitheliomas
D. Fibrofolliculomas
E. TricholemmomasCorrect Choice
The patient described may have Cowden's syndrome, an autosomal dominant condition caused by a defect in the PTEN tumor suppressor gene. Patients with Cowden's disease are at increased risk for thyroid and breast carcinoma. In addition, they characteristically have multiple hamartomatous polyps of the gastrointestinal tract that are typically benign. Cutaneous features of Cowden's syndrome which may serve as clues to the diagnosis include multiple oral papillomas with a "cobblestone" appearance on the lips, gingival, and buccal mucosa, acral keratotic papules on the dorsal hands and wrists, palmoplantar punctate keratoses and multiple facial tricholemmomas. Patients with this condition need careful malignancy surveillance.
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70) What is the inheritance pattern of dermatosis with acantholysis?
A. autosomal recessive
B. X-linked recessive
C. X-linked dominant
D. autosomal dominantCorrect Choice
E. sporadic
Hailey-Hailey, or Familial Benign Pemphigus, is an autosomal dominant genodermatosis which is caused by a mutation in ATP2C1. Vesicles and erythematous plaques develop in the skin folds such as axillae and groin area.
71) A patient with myotonic dystrophy and multiple skin lesions characterized by the pathology image shown most likely has activating mutations in which of the following?
A. desmoglein
B. desmoplakin
C. plakoglobin
D. beta-cateninCorrect Choice
E. alpha 6-beta 4 integrin
Myotonic dystrophy with multiple pilomatricomas is described above. Activating mutations in Beta-catenin are found in this syndrome. The other listed options are desmosomal proteins and are not involved in this syndrome.
72) Painful crises and 'whorled' corneal opacities are seen with which of the following enzyme abnormalities?
A. alpha-galactosidase ACorrect Choice
B. glucocerebrosidase
C. iduronate sulfatase
D. glucoronidase
E. homogentisic acid oxidase
Painful crises and whorled corneal opacities are found in Fabry disease which is caused by a defect in alpha-galactosidase A. The remaining conditions do not have these findings
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73) A patient with melanoma and a malignant glioma is diagnosed with Li-Fraumeni syndrome. Which of the following tumors occurs most frequently in this disease?
A. Breast carcinoma
B. Lung carcinoma
C. RhabdomyosarcomaCorrect Choice
D. Leukemia
E. Adrenocortical carcinoma
Li-Fraumeni syndrome is a familial tumor syndrome caused by mutations in the tumor suppressor gene p53. They are at risk for a wide range of malignancies with particularly high occurrences of soft tissue sarcomas, breast caner, brain tumors, acute leukemia, and adrenal cortical carcinoma. Soft tissue sarcomas are among the most common reported with this disease.
74) Most common malignancy to develop in a patient with tricholemmomas, acral verrucous papules and cobble-stoning of buccal and gingival mucosa?
A. Colon cancer
B. Breast cancer
C. Melanoma
D. Lymphoma
E. Thyroid cancerCorrect Choice
Cowden's syndrome is an autosomally dominant inherited defect of PTEN. Patient may present with multiple trichilemmoma, hamartomatous tumors of the breast, thyroid and endometrium, acral keratoses and papillomatous papules. Thyroid carcinoma is the most common form malignancy to arise in these patients
75) You are consulted on a patient with possible Nethertons Syndrome. Which location of the body would most likely have hairs demonstrating trichorrhexis invaginata?
A. none of these answers are correct
B. scalp
C. eyebrowCorrect Choice
D. all of these answers are correct
E. eyelash
Eyebrow hair is most common site with hairs demonstrating trichorrhexis invaginata.
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76) Beckwith-Wiederman syndrome is characterized by which of the following triads?
A. Epistaxis, telangictases, and gastrointestinal tract bleeding
B. Omphalocele, venous malformations, and ataxia
C. Exophthalmos, macroglossia, and gigantism Correct Choice
D. Hemangioblastomas, renal cysts and renal cell carcinoma
E. Enlarged limb, port wine stain, and deep venous thrombosis
Beckwith-Wiederman syndrome is also known as EMG syndrome as it includes exophthalmos, macroglossia, and gigantism. It is usually a sporadic condition but is sometimes caused by autosomal dominant mutations in p57. Clinical features include facial capillary malformations, macroglossia, visceromegaly with omphalocele, and hemihypertrophy associated with tumors (especially Wilm’s tumors).
77) A 16-month old girl presents with patchy alopecia, whorled erythematous scaly eruption, and asymmetric limb shortening. What laboratory or radiologic test may aid in diagnosis?
A. Alkaline phosphatase
B. Brain MRI
C. Bone filmsCorrect Choice
D. Chest radiograph
E. Complete blood count
The patient has Conradi-Hunermann Syndrome. This is a X-linked dominant disorder characterized by ichthyosiform erythroderma in Blaschko's lines in infancy which resolves with follicular atrophoderma, patchy alopecia, short stature, cataracts, scoliosis, assymetric limb shortening. Bone films will demonstrate stippled epiphyses. Ichthyosis and stippled epiphyses resolve after infancy.
78) A patient presents with multiple flesh colored papules on his face. The pathology report comes back as a fibrofolliculoma. He also has multiple lipomas. Which of the following neoplasms must you be concerned about?
A. Renal Cell Carcinoma
B. Colon carcinoma
C. All of the options are correctCorrect Choice
D. Medullary thyroid carcinoma
E. None of the options are correct
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Birt-Hogg-Dube syndrome is described above. Renal cell carcinoma is the most common association for internal malignancy, but medullary thyroid and colon carcinomas occur at an increased rate in these individuals also
79) Menke’s kinky hair syndrome is caused by a defect in:
A. Gap junction protein
B. Mitochondrial gene
C. Copper Transporting ATPaseCorrect Choice
D. DNA helicase
E. Proto-oncogene
Menke’s kinky hair syndrome is an x-linked recessive disorder caused by a mutation at Xq12 leading to defective intestinal copper transport
80) Retinal hemangioblastomas are found in which syndrome:
A. Kasabach-Merritt syndrome
B. Klippel-Trenaunay Weber syndrome
C. Sturge-Weber syndrome
D. Von-Hippel Lindau diseaseCorrect Choice
E. Osler-Weber-Rendu disease
Von Hippel-Lindau syndrome is an autosomal dominant condition caused by a defect in the VHL tumor suppressor gene. This disease is characterized by retinal hemangioblastomas, often resulting in visual impairment and blindness if left untreated. In addition, many tumors are seen including pheochromocytoma, renal cell carcinoma, and hemangioblastomas of the cerebellum, medulla, and spinal cord. Pancreatic and renal cysts are also a feature of this condition. Finally, polycythemia can occur as a result of erythropoietin production by renal cell carcinoma. Von Hippel-Lindau syndrome is a progressive, universally fatal condition which presents most often in the fourth decade of life
81) Mutations in calcium transporters cause which pair of diseases?
A. Chondrodysplasia punctata and CHILD syndrome
B. Darier’s disease and Hailey-Hailey disease Correct Choice
C. Lamellar ichthyosis and nonbullous congenital ichthyosiform erythroderma
D. Refsum syndrome and Sjogren-Larsson syndrome
E. Erythrokeratodermia variabilis and progressive symmetric erythrokeratodermia
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Darier’s disease and Hailey-Hailey disease are caused by mutations in the SERCA calcium ATPase. The former is characterized by hyperkeratotic papules in seborrheic areas, palmar keratoses and pits, red-white longitudinal nail bands, v-shaped distal nail nicks, and cobblestoning of oral and rectal mucosae. The latter is characterized by acantholytic erosions in skin folds
82) Which of the following is a potentially serious complication of the blue rubber bleb nevus syndrome?
A. Development of lymphedema
B. Gastrointestinal hemorrhage Correct Choice
C. Development of chondrosarcomas
D. Development of lymphedema
E. Development of angiosarcomas
Blue rubber bleb nevus syndrome is characterized by multiple tender venous malformations of skin and gastrointestinal tract, which can lead to gastrointestinal bleeding
83) A child with phenylketonuria likely presents with which cutaneous problems?
A. Alopecia universalis
B. Generalized hypopigmentationCorrect Choice
C. Leg ulcers
D. Blue-gray generalized hyperpigmentation
E. Generalized hyperpigmentation
Phenylketonuria is an autsomal recessive disorder caused by a mutation on the long arm of chromosome 12. A deficiency of phenylalanine hydroxylase or its cofactor tetrahydrobiopterin leads to accumulation of phenylalanine. Clinical features include generalized hypopigmentation, eczematous dermatitis, sclerodermoid changes, seizures, psychomotor delay, urine with “mousy” odor, mental retardation
84) Patients with Chondrodysplasia punctata can have findings of stippled epiphyses on X-ray examination. Which other x-linked dominant condition can have stippled epiphyses?
A. CHILD syndromeCorrect Choice
B. Bazex syndrome
C. Incontinentia Pigmenti
D. Goltz syndrome
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E. Focal Dermal Hypoplasia
All of the syndromes listed have X-linked dominant inheritance. CHILD syndome also has findings of stippled epiphyses. Incontinentia pigmenti is caused by defecdts in the NEMO gene. Findings include peg/conical teeth, eye and CNS defects and alopecia. There are no bone abnormalities. Focal Dermal Hypoplasia, otherwise known as Goltz syndrome has findings of linear atrophy following Blaschko's lines with areas of fat herniation, mucocutaneous papillomas and pits, alopecia, nail dystrophy, tooth abnormalities and osteopathia striata (striations of the long bones). Bazex syndrome is associated with follicular atrophoderma, hypohidrosis, hypotrichosis and multiple basal cell carcinomas. There are no bone abnormalities associated
85) Comma-shaped corneal opacities are characteristic of which type of ichthyosis?
A. X-linked ichthyosis Correct Choice
B. Nonbullous congenital ichthyosiform erythroderma
C. Lamellar ichthyosis
D. Ichthyosis vulgaris
E. Refsum syndrome
X-linked ichthyosis patients have comma-shaped corneal opacities that are asymptomatic yet highly characteristic.
86) Painful crises and 'whorled' corneal opacities are seen with which of the following enzyme abnormalities?
A. iduronate sulfatase
B. glucoronidase
C. glucocerebrosidase
D. alpha-galactosidase ACorrect Choice
E. homogentisic acid oxidase
Painful crises and whorled corneal opacities are found in Fabry disease which is caused by a defect in alpha-galactosidase A. The remaining conditions do not have these findings.
87) In chronic granulomatous disease, the diagnosis is made by which of the following tests?
A. Assay for fumarate hydratase
B. Nitroblue tetrazolium reduction assayCorrect Choice
C. Assay for sphingomyelinase
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D. Skin biopsy
E. Assay for glucocerebrosidase
Chronic granulomatous disease is diagnosed by the nitroblue tetrazolium reduction assay. The abnormal white blood cells cannot reduce dye due to the inability to produce the respiratory burst. This is needed to kill catalase positive organisms after phagocytosis. Fumarate hydratase is defective in familial multiple cutaneous leiomyomatosis, sphingomyelinase in Niemann-Pick disease and glucocerebrosidase in Gaucher disease
88) Milia, atrophoderma vermiculata and eruptive lesions shown in the pathologic image are characteristic of which of the following syndromes?
A. Banayan-Riley-Ruvalcaba
B. Gorlin
C. Nicolau-BalusCorrect Choice
D. Cowden
E. Birt-Hogg-Dube
Nicolau-Balus syndrome is characterized by eruptive syringomas (shown in the path image), milia an datrophoderma vermiculata. Cowden syndrome is associated with trichilemmomas, Birt-Hogg-Dube with fibrofolliculoma, and Banayan-Riley-Ruvalcaba is not associated with an adnexal neoplasm
89) Which of the following bony defect is found in CHILD syndrome?
A. Calcification of falx cerebri
B. Osteopoikilosis
C. Stippled epiphysesCorrect Choice
D. Sphenoid wing dysplasia
E. Polyostotic fibrous dysplasia
CHILD syndrome is an X-linked dominant syndrome which is lethal in males. It is caused by a peroxisomal biogenesis disorder. It is characterized by unilateral ichthyosiform erythroderma, limb/visceral hypoplasia, and stippled epiphyses. Stippled epiphyses can also be seen in chondrodysplasia punctata. Polyostotic fibrous dysplasia is found in McCune-Albright syndrome, calcification of falx cerebri in Gorlin's syndrome, osteopoikilosis in seen in Buschke-Ollendorf syndrome
90) Epidermolysis bullosa with muscular dystrophy is caused by mutations in which of the following?
A. Keratins 5 and 14
B. Loricrin
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C. Collagen 17
D. Plectin Correct Choice
E. Collagen 7
Epidermolysis bullosa with muscular dystrophy is caused by mutations in plectin
91)Which of the following syndromes is associated with hematologic abnormalities?
A. Klippel-Trenaunay-Parks-Weber
B. Kasabach-Merritt syndromeCorrect Choice
C. Bloom’s syndrome
D. Blue rubber bleb nevus syndrome
E. Sturge Weber disease
Kasabach-Merritt syndrome is associated with hematologic abnormalities, such as thrombocytopenia, microangiopathic hemolytic anemia, disseminated intravascular coagulation. The condition develops from platelet-trapping within a large hemangioma, most commonly a kaposiform hemangioendothelioma in the retroperitoneal location.
92) Which of the following is caused by a defect in lysosomal transport:
A. Chediak-higashiCorrect Choice
B. oculocutaneous albinism II
C. Piebaldism
D. oculocutaneous albinism I
E. Bloom’s syndrome
Chediak higashi is an autosomal recessive disorder caused by a mutation in the LYST gene codes for a lysosomal tracking protein. This protein regulates microtubule mediated lysosomal fusion. A defect in this gene leads to giant lysosomal granules seen in neutrophils (leading to defecting phagocytosis and decreased chemotaxis), melanocytes (pigment dilution), and neurons. OCA1 is tyrosinase negative albinism; OCA2 is tyrosinase positive albinism with a mutation in P gene on chromosome 15
93) Which keratins are expressed in the suprabasal palmoplantar epidermis?
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A. Keratins 4 and 13
B. Keratins 8 and 18
C. Keratins 1 and 9 Correct Choice
D. Keratins 5 and 14
E. Keratins 1 and 10
Keratins are expressed in pairs of acidic and basic keratins and are tissue- and differentiation-specific. Keratins 1 and 9 are expressed in the suprabasal palmoplantar epidermis, keratins 1 and 10 in suprabasal nonpalmoplantar epidermis, keratins 2e and 10 in the granular layer, keratins 4 and 13 in mucosal epithelium, keratins 5 and 14 in the basal layer, and keratins 8 and 18 in simple epithelium.
94) Dermatofibrosis lenticularis disseminata is seen in which of the following conditions?
A. Pseudoxanthoma elasticum
B. Focal dermal hypoplasia
C. Ehlers-Danlos syndrome
D. Marfan syndrome
E. Buschke-Ollendorf syndrome Correct Choice
Buschke-Ollendorf syndrome is an autosomal dominant disorder characterized by dermatofibrosis lenticularis disseminata (cutaneous elastomas distributed symmetrically over the buttocks, trunk and proximal extremities), and osteopoikilosis (round opacities in bones
95) A patient with 20 nail dystrophy, steatocystoma multiplex and natal teeth likely has a mutation in the genes coding for:
A. Laminin 5
B. Plakophilin 1
C. Keratins 5 &14
D. Keratins 6b & 17Correct Choice
E. Keratins 6 &16
Pachyonychia congenital is an autosomal dominant condition with 20 nail dystrophy. The patient described has Type II (Jackson-Sertole) disease, which includes steatocystoma multiplex, natal teeth, multiple cysts, and micropthalmia, and is caused by mutations in keratins 6b& 17. Type I (Jadassohn-Lewandowsky) also includes focal symmetric PPK, follicular hyperkeratosis, oral leukokeratoses and is caused by mutations in keratins 6 &16. Type III includes the clinical features of type I + corneal leukokeratosis. Mutations in keratins 5&14 represents EB simplex, Laminin 5
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mutation is seen in Junctional EB, and plakophilin 1 mutation is seen in ectodermal dysplasia with skin fragility
96) Premalignant leukoplakia of the oral mucosa is associated with:
A. Werner Syndrome
B. Bloom syndrome
C. Rothmund-Thomson syndrome
D. Dyskeratosis CongenitaCorrect Choice
E. Xeroderma Pigmentosum
Dyskeratosis Congenita (also known as Zinsser-Engman-Cole syndrome) is thought to have two modes of inheritance. The more common X-linked disorder is due to a mutation in the Dyskerin gene, while the autosomal dominant form is due to a mutation in TERC, a telomerase RNA component. Clinical features include reticulated gray-brown hyperpigmentation, paloplantar hyperkeratosis, alopecia, onychodystrophy, premalignant leukoplakia of any mucosal surface, and mental retardation
97) Which of the following disorders is associated with delayed separation of the umbilical cord?
A. Leukocyte adhesion deficiency type 1 (LAD-1)Correct Choice
B. Myeloperoxidase deficiency
C. X-linked agammaglobulinemia
D. Severe combined immunodeficiency disorder(SCID)
E. Immunedysregulation, polyendocrinopathy, enteropathy, x-linked (IPEX)
LAD-1 manifests as a B2-integrin deficiency and often times presents as at birth with a delayed umbilical cord separation.
98) Mucosal neuromas, pheochromocytoma and medullary thyroid carcinoma in a patient with a marfanoid body habitus is associated with which of the following gene defects?
A. RET proto-oncogeneCorrect Choice
B. STK11
C. BHD
D. Menin
E. PTEN
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The RET proto-oncogene is mutated in Multiple Endocrine Neoplasia type II. Type IIb is described above. Other findings include rare parathyroid abnormalities, megacolon, thickened lips and thick, everted upper eyelids. Menin is associated with MEN type I, PTEN with Cowden disease, BHD with Birt-Hogg-Dube syndrome and STK11 with Peutz-Jeghers syndrome
99) In a patient suspected of having multiple endocrine neoplasia type IIb, which lab test would be appropriate?
A. Parathyroid hormone
B. Cortisol
C. CalcitoninCorrect Choice
D. Glucagon
E. Calcium
Multiple endocrine neoplasia (MEN) syndrome type Iib, also called multiple mucosal neuroma syndrome is an autosomal dominant condition due to a defect in the RET protooncogene on chromosome 10q11.2. This rare condition is associated with mucosal neuromas on the tongue and lips, medullary thyroid carcinoma, pheochromocytoma, and gastrointestinal ganglioneuromatosis. In addition, patients can also present with a marfanoid habitus and facial dysmorphism. Mucosal neuromas can be a dermatologic clue to the underlying diagnosis as these lesions appear during early childhood and present as pink, pedunculated nodules. As the major cause of mortality in these patients is medullary thyroid cancer, which nearly all patients will have by early adulthood, aggressive screening, with serial calcitonin level, and prophylactic thyroidectomy are warranted.
100) What is the gene defect in this condition, which is also called Mendes da Costa syndrome?
A. keratin 1 and 10
B. SPINK5
C. connexin 31Correct Choice
D. SLURP-1
E. connexin 26
Mendes da COsta syndrome is also called Erythrokeratoderma Variabilis. It is an autosomal dominantly inherited due to a mutation in connexin 31 or connexin 30.3. It is characterized by transient geographic patches of erythema and hyperkeratotic plaques
101) The hair abnormality shown in the image is characteristic of which of the following diseases?
A. TrichothiodystrophyCorrect Choice
B. Monilethrix
C. Bjornstad syndrome
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D. All of the options are correct
E. Naxos disease
The hair abnormality shown is trichoschisis, clean breaks of the hair shaft which occurs in trichothiodystrophy. Also commonly seen is the "tiger-tail" banding pattern of the hair when placed under polarized light. The other options do have hair shaft abnormalities, but not trichoschisis
102) The treatment for acrodermatitis enteropathica is:
A. Vitamin B12 supplementation
B. Zinc supplementationCorrect Choice
C. Phlebotomy
D. Iron supplementation
E. Vitamin B1 supplementation
Acrodermatitis enteropathica is due to a defect in zinc absorption and will respond to zinc supplementation. Iron, Vitamin B1/12 supplementation will not result in improvement in this condition. Findings include periorificial, scalp, and acral dermatitis, scaling, vesicles/bullae, erosions, alopecia, diarrhea and stomatitis
103) In patients with diffuse congenital hemangiomatosis, the most common site for extracutaneous involvement is the :
A. Brain
B. Thyroid
C. LiverCorrect Choice
D. Lungs
E. Colon
Diffuse congenital hemangiomatosis is characterized by multiple hemangiomas with the liver being the most common extracutaneous site, followed by the lungs. Liver hemangioma may be complicated by hepatomegaly, obstructive jaundice, and portal hypertension
104) A deficiency in sialophorin, a surface glycoprotein, is thought to play a role in which genetic disorder?
A. Bloom Syndrome
B. Chediak-higashi syndrome
C. Cornelia de Lange syndrome
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D. Werner syndrome
E. Wiskott-aldrich syndromeCorrect Choice
Wiskott-Aldrich syndrome is an x-liked recessive disorder localized to Xp11.3. The gene involved codes for WAS, and the protein product has been implicated in lymphocyte and megakaryocyte signal transduction
105) Sphenoid wing dysplasia is seen in:
A. Tay Syndrome
B. NF-1Correct Choice
C. NF-2
D. Mafucci syndrome
E. Tuberous sclerosis
Sphenoid wing dysplasia is seen in neurofibromatosis type I. Patients with Tay syndrome have short stature, patients with tuberous sclerosis have phalangeal cysts and periosteal thickening, patients with Mafucci syndrome have enchondromas and short stature, and patients with NF-2 do not have any characteristic musculoskeletal findings
106) A patient Buschke-Ollendorff syndrome has osteopoikilosis and which cutaneous finding?
A. Epidermal nevi
B. Café au lait macules
C. Waxy papules along the eyelids
D. Port wine stain
E. Juvenile elastomaCorrect Choice
Buschke-Ollendorf syndrome is an autosomal dominant syndrome associated with increased elastic fiber in the skin. Key features include dermatofibrosis lenticularis disseminata (also called juvenile elastomas) and osteopoikilosis
107) Which of the following is NOT part of the Carney complex?
A. Endocrine abnormalities
B. Peg or conical teethCorrect Choice
C. Pigmented skin lesions
D. Cardiac, cutaneous or mammary myxomas
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E. Primary pigmented nodular adrenocortical disease
Peg/conical teeth are not part of the Carney complex. This is found in incontinentia pigmenti and anhidrotic ectodermal dysplasia. The remaining skin findings are part of this complex sometimes known as NAME syndrome. It consists of multiple, diffuse mucocutaneous lentigines, cardiac and subcutaneous myxomas and endocrine abnormalities may be present. Other findings include: testicular tumors, thyroid disease, primary pigmented nodular adrenocortical disease, psammomatous melanotic schwannomas and hormone-secreting pituitary adenomas
108) A patient presents with the multiple painful papules on the abdomen with pathology as shown in the image. They report that their father had similar skin lesions. What enzyme defect is the most likely cause?
A. Steroid sulfatase
B. homogentisic acid oxidase
C. glucocerebrosidase
D. alpha-galactosidase
E. fumarate hydrataseCorrect Choice
Fumarate hydratase has been implicated in familial multiple cutaneous leiomyomatosis. Steroid sulfatase is defective in x-linked ichthyosis, alpha-galactosidase in Fabry disease, homogentisic acid oxidase in alkaptonuria and glucocerebrosidase in Gaucher disease.
109) Cutaneous osteomas are seen in which syndrome?
A. Carney complex
B. Albright hereditary osteodystrophy Correct Choice
C. Gaucher’s syndrome
D. Waardenburg syndrome
E. LEOPARD syndrome
Albright hereditary osteodystrophy is caused by mutations in the Gs subunit of adenylate cyclase. There is calcification and ossification due to pseudohypoparathyroidism, absent 4th knuckle, and hypogonadism.
110) What is the genetic defect of this autosomal dominant disorder?
A. Calcium ATPase 2C1Correct Choice
B. PTPN11
C. SPINK5
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D. Calcium ATPase 2A2
E. PTEN
Hailey-Hailey is an autosomal dominant disorder that usually affects the intertriginous areas. Clinically, there is erythema and linear fissures of the axilla and groin. On pathology, the characteristic finding is dyskeratosis in a "dilapidated brick wall" pattern. The gene defect responsible is calcium ATPase 2C1
111) Primary pigmented nodular adrenocortical disease and psammomatous melanotic schwannomas are characteristic of which of the following syndromes?
A. McCune-Albright syndrome
B. Tuberous sclerosis
C. Gaucher’s syndrome
D. Hypomelanosis of Ito
E. Carney complex Correct Choice
Carney complex is an autosomal dominant disorder caused by mutations in PRKAR1A (protein kinase A regulatory subunit 1-alpha). Key features include cardiac, cutaneous and mammary myxomas, pigmented skin lesions, endocrine abnormalities (pituitary, testicular, thyroid, etc), primary pigmented nodular adrenocortical disease, and psammomatous melanotic schwannomas
112) A triangular-shaped lunula is a characteristic finding in which disease?
A. incontinentia pigmenti
B. Darier's disease
C. dyskeratosis congenita
D. nail-patella syndromeCorrect Choice
E. epidermal nevus syndrome
Nail-patella syndrome, also called hereditary osteo-onychodysplasia is a rare autosomal dominant condition caused by a defect in the LMX1B gene. It is characterized by triangular lunulae, palmoplantar hyperhidrosis, renal dysplasia, glomerulonephritis, and hyperpigmentation of the papillary margin of the iris, an ophthalmologic finding also known as Lester iris. Other nail findings include micronychia with hemionychia, anonychia, and longitudinal fissures. Bony findings include absent or hypoplastic patella, posterior iliac horns, radial head subluxation, thickened scapulae, and scoliosis.Nail findings in Darier's disease include red and white longitudinal bands, subungual hyperkeratosis and V-shaped nicking of the distal nail plate. Dystrophic nails with longitudinal ridges, pterygium, and atrophic or absent nails can be found in dyskeratosis congenita. Dystrophic changes of the nails can be seen in approximately 5-10% of patients with incontinentia pigmenti.
113) A patient with renal cell carcinoma caused by mutations in fumarate hydratase deficiency likely suffers which of the following conditions?
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A. Multiple endocrine neoplasia
B. Birt-Hogg-Dube syndrome
C. Von-Hippel-Lindau syndrome
D. Familial multiple cutaneous leiomyomatosis Correct Choice
E. Cowden syndrome
Familial multiple cutaneous leiomyomatosis is an autosomal dominant condition caused by mutations in the fumarate hydratase gene. Clinically, there are multiple cutaneous leiomyomas, uterine leiomyomas and leiomyosarcomas, as well as renal cell carcinomas
114) A patient presents with several light blue cyst-like lesions on the eyelid. They consult their list of problems and bring up plantar hyperkeratosis and dysplastic toenails. On oral exam, you note that they have both upper and lower dentures. The patient relates that after losing their "baby teeth", only 3 teeth grew in their place. What syndrome does this person most likely have?
A. Cowden syndrome
B. Cronkhite-Canada
C. Hypohidrotic ectodermal dysplasia
D. Schopf-Schulz-PassargeCorrect Choice
E. Gardner syndrome
Schopf-Schulz-Passarge syndrome is associated with hydrocystomas of the eyelids, hypotrichosis (near complete loss of hair early in life), hypodontia, nail abnormalities and multiple palmoplantar eccrine syringofibroadenomas. The other listed syndromes do not fit the description above
115) The presence of natal teeth and pincer nails suggests which disease entity?
A. anhidrotic ectodermal dysplasia
B. pachyonychia congenitaCorrect Choice
C. congenital syphillis
D. thalidomide exposure in utero
E. incontinentia pigmenti
Pachyonychia congentia is an autosomal dominant condition characterized by a constellation of findings affecting ectodermal structures. These include the presence of natal teeth, steatocystoma multiplex, follicular hyperkeratosis of the knees, elbows and extensor extremities, eruptive vellus hair cysts, and oral leukokeratosis which is not pre-malignant. In addition, nail findings include twenty-nail dystrophy, subungual hyperkeratosis with increase transverse curvature ("pincer nails") and candidal paronychia. There are two forms of pachyonychia congenital: Type 1 (Jadassohn-Lewandowsky syndrome) caused by defects in keratin 6a and 16, and Type 2 (Jackson-Lawler type)
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caused by defects in keratins 6b and 17.Anhidrotic ectodermal dysplasia is associated with peg-shaped teeth, hypoanodontia, and a non-specific nail dystrophy. Likewise, incontientia pigmenti also is characterized by anodontia and peg-shaped teeth and dystrophic changes of the nail. Finally congenital syphilis is a well-recognized cause of pegged teeth. Limb deformities are the most serious sequelae of thalidomide exposure in utero
116) A patient with pseudoherpetic keratitis and a painful PPK would improve with a diet low in:
A. Zinc
B. Biotin
C. Cytosine
D. Tyrosine/PhenylalanineCorrect Choice
E. Glycine
Pseudoherpetic keratitis and a painful PPK describes a patient with Richner-Hanhart syndrome (tyrosenemia type II). Treatment is with a diet low in tyrosine and phenylalanine. A diet low in glycine, cytosine, biotin or zinc would not be helpful in this syndrome
117) A patient with multiple facial trichilemmomas is at risk of which of the following cancers?
A. Basal cell carcinoma
B. Cylindroma
C. Breast carcinoma Correct Choice
D. Oral squamous cell carcinoma
E. Acute leukemia
Cowden syndrome (multiple hamartoma syndrome) is an autosomal dominant disorder caused by mutations in PTEN, a phosphatase that dephosphorylates tyrosine, serine, and threonine. Clinically, there are numerous facial trichilemmomas, oral papillomas, acral keratotic papules, sclerotic fibromas, breast fibroadenomas and adenocarcinomas, thyroid adenomas and adenocarcinomas, and hamartomatous polyps of the gastrointestinal tract
118) Which of the following signs is not a criteria for the diagnosis of Neurofibromatosis type I?
A. Sphenoid dysplasia
B. Axillary freckling
C. Greater than 5 café-au-lait macules
D. Optic gliomas
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E. Bilateral vestibular schwannomasCorrect Choice
Bilateral vestibular schwannomas are related to type II neurofibromatosis. The remaining options are diagnostic criteria for NF-1.
119) Patients with homocystinuria are deficient in:
A. Transglutaminase
B. Lysyl oxidase
C. Cystathionine synthetaseCorrect Choice
D. Alpha galactosidase A
E. Steroid sulfatase
Homocystinuria is an autosomal recessive disease caused by a deficiency of cystathionine synthetase. Manifestations of this condition may include mental retardation, marfanoid habitus, malar flush, ectopic lentis, embolic phenomena and leg ulcers
120) A patient presents with bilateral retinal hemangioblastomas and a capillary malformation on her neck. Which gene mutation is most likely?
A. MFH1
B. PTH/PTHrP type I receptor
C. VEGF receptor-3
D. Endoglin
E. VHLCorrect Choice
These findings are most characteristic of Von Hippel-Lindau syndrome. VHL is a tumor suppressor gene which is mutated in this syndrome. Other findings include: renal and pancreatic cysts/carcinoma, pheochromocytoma, and cerebellar/other CNS hemangioblastomas. Endoglin is defective in Osler-Weber-Rendu, PTH/PTHrP type I receptor in Maffucci syndrome, VEGF receptor-3 in Nonne-Milroy disease (hereditary lymphedema) and MFH1 in lymphedema and ptosis syndrome
121) The gene defect in LEOPARD syndrome is:
A. ATM
B. KIP2
C. PTPN11 Correct Choice
D. PRKAR1A
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E. Neurofibromin
PTPN11 gene is mutated in LEOPARD syndrome. This syndrome consists of the complex of Lentigines, EKG abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retardation of growth and Deafness. PRKAR1A is associated with the Carney complex of diseases. KIP2 is found in 15% of cases of Beckwith-Wiedermann syndrome. ATM is mutated in ataxia telangectasia syndrome and Neurofibromin in Neurofibromatosis type I.
122) Hereditary Hemorrhagic Telangiectasia syndrome is transmitted in an autosomal dominant fashion and can have two variants. Type I is linked to defects in HHT1, the endoglin gene. Type II is linked to defects in HHT2, the ALK1 gene. What feature that differentiates type I from type II clinically?
A. Type I families have an increase incidence of pulmonary arteriovenous fistulasCorrect Choice
B. None of the answers are correct
C. Type I families have an increased incidence of hepatic arteriovenous malformations
D. Type II families have an increased incidence of pulmonary arteriovenous fistulas
E. Type II families have a decreased incidence of hepatic arteriovenous malformations
There is an increased incidence of pulmonary arteriovenous fistulas in HHT type I. Type II has an increased incidence of hepatic arteriovenous malformations.
123) Connexin 30 (GJB6 gene) is defective in which of the following syndromes?
A. Vohwinkel syndrome
B. Erythrokeratoderma variabilis
C. Clouston syndromeCorrect Choice
D. KID syndrome
E. Vohwinkel syndrome variant
Clouston syndrome is associated with a defect in Connexin 30 (GJB6 gene). Findings include palmoplantar keratoderma with transgradiens, dystrophic nails, sparse hair with absent body, eyelash, eyebrow hair after puberty. KID syndrome and Vohwinkel syndrome are associated with a defect in Connexin 26 (GJB2). Vohwinkel syndrome variant is associated with a loricrin defect. Erythrokeratoderma variabilis has mutations in Connexin 31 (GJB3) and 30.3(GJB4).
124) What protein is deficient in the condition shown?
A. Desmoglein 3
B. SPINK5
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C. Calcium ATP’ase IIA2
D. Calcium ATP’ase IIC1Correct Choice
E. PEX-7
The picture shown is Hailey-Hailey disease. This is an autosomally dominant condition with a defect in Calcium ATP’ase IIC1. On H&E stain, an acantholytic “dilapidated brick wall” appearance is seen. Calcium ATP’ase IIA2 is defective in Darier’s Disease, PEX-7 in autosomal recessive type Conradi-Hunermann disease, SPINK5 in Netherton’s disease and Desmoglein 3 in pemphigus vulgaris
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