201 - 328

Question 1

A patient presents with focal symmetric palmoplantar keratoderma, thickened, hyperkeratotic fingernails and toenails with a “pincer” appearance and frequent staph and candida paronychial infections, follicular hyperkeratosis of the knees and elbows and oral leukokeratosis. The patients mother and grandfather both have similar skin findings. Which syndrome is described?
1 Jadassohn-Lewandowsky syndrome
2 Jackson-Lawler syndrome
3 Schafer-Branauer syndrome
4 Pachyonychia congenita tarda
5 None of the options are correct

Answer 1

The description above is the classic description for pachyonychia congenita (PC) type I or Jadassohn-Lewandowsky syndrome. Jackson-Lawler syndrome is PC type II, Schafer-Branauer syndrome is PC type III and pachyonychia congenita tarda is PC type IV.
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Question 2

Eyelid string of pearls are seen in which of the following conditions?
1 Focal dermal hypoplasia
2 Lipoid proteinosis
3 Hutchinson-Gilford syndrome
4 Beare-Stevenson cutis gyrata syndrome
5 Gaucher�s disease
Lipoid proteinosis is an autosomal recessive condition characterized by yellow papules on the face and oropharynx, eyelid string of pearls, hoarse voice, verrucous nodules of elbows and knees, and bean-shaped temporal and hippocampal calcification with occasional seizures. Histologically, there are PAS+ deposits in the affected tissue.
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Question 3

Which of the following is caused by a defect in a gap junction protein?
1 Epidermolysis bullosa simplex
2 Hailey-hailey
3 Erythrokeratoderma variabilis
4 Dyskeratosis congenita
5 Bullous ichthyosis of siemens

Answer 3

Erythrokeratoderma variabilis is also known as Mendes da Costa Syndrome. It is caused by a defect in connexin 31, a gap junction protein. EB simplex is caused by a mutation in keratins 5 & 14, Hailey-Hailey is caused by a mutation in calcium transporters, dyskeratosis congenita is caused by a defect in rRNA synthesis, and bullous icthyosis of Siemens is caused by mutations in keratin 2e.
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Question 4

Painful crises and ‘whorled’ corneal opacities are seen with which of the following enzyme abnormalities?
1 Homogentisic acid oxidase
2 Alpha-galactosidase A
3 Glucocerebrosidase
4 Iduronate sulfatase
5 Glucoronidase

Answer 4

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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Question 5

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?
1 Wilsons
2 Hemochromatosis
3 Hartnup Disease
4 Fabry
5 Gaucher’s

Answer 5

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).
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Question 6

Ichthyosis hystrix is characterized by the following gene defects?
1 Keratins 1 and 9
2 Keratins 1 and 10
3 Keratins 5 and 14
4 Keratins 6 and 16
5 None of these answers are correct

Answer 6

Ichthyosis hystrix or extensive epidermal nevi occurs secondary to a somatic mosaicism for keratins 1 and 10. If the mosaicism occurs on gonadal cells, offspring may have full blown epidermolytic hyperkeratosis (EHK).
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Question 7

A 20-year old male with a history of pheochromocytoma and medullary thyroid cancer presents with mucosal papules. His overall body appearance is most likely to demonstrate:
1 Cushingoid features
2 Marfanoid features
3 Short stature
4 Lipodystrophy
5 Unilateral limb shortening

Answer 7

This patient has multiple endocrine neoplasia type IIb (MEN IIb) characterized by pheochromocytoma, thyroid cancer, and rare parathyroid carcinoma as well as mucosal neuromas cutaneously. These patients have a marfanoid body habitus. This syndrome is caused by the RET proto-oncogene.
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Question 8

A patient with a port wine stain covering one enlarged leg likely has which of the following associated symptoms?
1 Lymphatic and deep venous insufficiency
2 Visceromegaly with omphalocele
3 Bilateral retinal hemangioblastomas
4 Enchondromas
5 Distichiasis

Answer 8

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.
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Question 9

The x-linked recessive type of dyskeratosis congenita is:
1 Dyskerin
2 TERC
3 CDKN2A
4 PTEN
5 Menin

Answer 9

The dyskerin gene, whose product is involved in ribosomal RNA synthesis, is mutated in X-linked recessive dyskeratosis congenita. TERC is linked with autosomal domininant transmission of the syndrome. CDKN2A is involved in familial dysplastic nevi/melanoma syndrome, PTEN in Cowden syndrome and Menin in MEN type I.
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Question 10

The main cause of death in patients with dyskeratosis congenita is which of the following?
1 Oral squamous cell carcinoma
2 Leukemia
3 Renal cell carcinoma
4 Pancytopenia
5 Atherosclerotic heart disease

Answer 10

Dyskeratosis congenita is usually inherited in an X-recessive fashion due to mutations in the dyskerin gene, which is involved in ribosomal RNA synthesis. The less common autosomal dominant form is caused by mutations in the telomerase gene. Clinically, there is reticulated pigmentation of skin, poikiloderma, alopecia, nail atrophy, premalignant oral leukoplakia, and Fanconi-type pancytopenia resulting in early death.
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Question 11

Beare-Stevenson cutis gyrata syndrome is linked with mutations in:
1 Fibroblast growth factor receptor 2
2 BSCL2
3 LMNA
4 ATP7A
5 None of these answers are correct

Answer 11

Beare-Stevenson ciutis 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.
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Question 12

Patients with progeria typically die of which of the following conditions?
1 Infection
2 Metastatic carcinoma
3 Atherosclerotic heart disease
4 Nail atrophy
5 Progressive systemic sclerosis

Answer 12

Progeria (Hutchinson-Gilford syndrome) is a sporadic condition characterized by lipoatrophy, sclerodermoid skin, alopecia, nail atrophy, craniomegaly with small face, muscle/bone wasting, and severe premature atherosclerosis resulting in early death.
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Question 13

Mutations in which of the following receptors underlie chronic mucocutaneous candidiasis disease (CMCD)?
1 IL-12 receptor
2 IL-15 receptor
3 AIRE receptor
4 IL-17 receptor
5 IL-23 receptor

Answer 13

Chronic mucocutaneous candidiasis disease (CMCD) is characterized by recurrent or persistent infections of the skin, nails, and oral and genital mucosae caused by Candida albicans and, to a lesser extent, Staphylococcus aureus, in patients with no other infectious or autoimmune manifestations. Mutations in IL-17 receptor A (IL-17RA, autosomal recessive) and IL-17 receptor F (IL-17F, autosomal dominant) have been reported. IL-17RA deficiency is complete, abolishing cellular responses to IL-17A and IL-17F homo- and heterodimers. By contrast, IL-17F deficiency is partial, with mutant IL-17F-containing homo- and heterodimers displaying impaired, but not abolished, activity.
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Question 14

Connexin 30 (GJB6 gene) is defective in which of the following syndromes?
1 KID syndrome
2 Vohwinkel syndrome
3 Vohwinkel syndrome variant
4 Clouston syndrome
5 Erythrokeratoderma variabilis

Answer 14

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).
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Question 15

Ectopia lentis (downward displacement of the lens) is characteristic of:
1 Marfan syndrome
2 Homocystinuria
3 Phenylketonuria
4 Multiple Carboxylase deficiency
5 Ehlers-Danlos syndrome

Answer 15

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.
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Question 16

Epistaxis in early childhood to teens followed by multiple cutaneous and gastrointestinal telangectasias describes which of the following syndromes?
1 Hereditary Hemorrhagic Telangiectasia syndrome
2 Maffucci syndrome
3 CREST syndrome
4 Ataxia telangectasia
5 Fabry disease

Answer 16

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.
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Question 17

Adenosine deaminase deficiency is seen in which immunodeficient disease?
1 Wiskott-Aldrich syndrome
2 Chronic granulomatous disease
3 Job syndrome
4 Severe combined immunodeficiency syndrome
5 Leineri’s disease

Answer 17

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).
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Question 18

Ichthyosis with confetti is a severe, sporadic ichthyosis caused by mutations in which gene?
1 Keratin 1
2 Keratin 2e
3 Keratin 10
4 Keratin 14
5 Keratin 15

Answer 18

Ichthyosis with confetti, a severe, sporadic skin disease in humans, is caused by mutations in the gene encoding keratin 10 (KRT10); all result in frameshifts into the same alternative reading frame, producing an arginine-rich C-terminal peptide that redirects keratin 10 from the cytokeratin filament network to the nucleolus.
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Question 19

Findings of eyelid papules (string of pearls) and a hoarse cry in infants is characteristic of which of the following syndromes?
1 Lipoid proteinosis
2 Amyloidosis
3 Pseudoxanthoma elasticum
4 Disseminated xanthomas
5 None of these answers are correct

Answer 19

Findings of the eyelid string of pearls and a hoarse cry during the first years of life (due to vocal cord infiltration) is characteristic of Lipoid Proteinosis (AKA Urbach-Wiethe disease or Hyalinosis cutis et mucosae). It is an autosomal recessive condition with mutations in the extracellular matrix protein 1 gene. Other findings include calcifications of the temporal lobe and hippocampus, hairloss, atrophic scars and waxy papules on the face, verrucous nodules and a thick tongue. The other conditions could be considered on the differential for Lipoid Proteinosis, but do not have the findings described above.
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Question 20

What is the most likely syndrome that this woman has in this photograph?
1 A. Klippel Trenaunay Weber
2 Filariasis
3 Neurofibromatosis
4 Proteus syndrome
5 Turner syndrome

Answer 20

Klippel-Trenaunay Weber syndrome is characterized by a triad of port-wine stain, varicose veins, and bony and soft tissue hypertrophy involving an extremity. Filariasis is an acquired infection that leads to obstruction and scarring of the lymphatics. Neurofibromatosis is associated with neurofibromas, café-au-lait macules and Lisch nodules, but not with lymphedema and vascular malformations. Proteus syndrome is associated with vascular abnormalities, lipomas and asymmetric limb hyperplasia, and plantar connective tissue nevi, but usually not lymphedema. Lymphedema of the dorsal hands and feet can be seen in Turner syndrome, but typically not this extensive.
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Question 21

Which of the following is not classically associated with pheochromoctyoma?
1 Multiple Endocrine Neoplasia Type IIA
2 Multiple Endocrine Neoplasia Type IIB
3 Von-Hippel-Lindau Syndrome
4 Cobb Syndrome
5 Neurofibromatosis

Answer 21

Cobb syndrome is a sporadic disease characterized by cutaneous vascular malformations associated with malformations of the spinal cord.
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Question 22

Which of the following medications is a teratogen associated with a aplasia cutis congenita?
1 Propranolol
2 Methimazole
3 Lithium
4 Alcohol
5 Warfarin

Answer 22

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.
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Question 23

Palmoplantar keratoderma with deafness is caused by a defect in which gene?
1 SLURP-1
2 Plakophilin
3 Mitochondrial serine transferase RNA
4 Lysosomal papain like cysteine proteinase
5 Unknown

Answer 23

Palmoplantar keratoderma with deafness is caused by a defect in mitochondrial serine transferase RNA. A defect in SLURP-1 causes Mal de Meleda. A defect in plakophilin causes ectodermal dysplasia with skin fragility. A defect in cathepsin C lysososomal papain like cysteine proteinase causes Papillon LeFevre and Haim Munk.
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Question 24

Junctional epidermolysis bullosa with pyloric atresia is associated with mutations in:
1 The alpha-6 subunit of integrin
2 The beta-4 subunit of integrin
3 Both subunits of integrin can have mutations causing this type of junctional epidermolysis bullosa
4 Plectin
5 Laminin 5

Answer 24

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.
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Question 25

What cutaneous manifestation is associated with familial cerebral cavernomas?
1 Verrucous hemangioms
2 Glomeruloid hemangiomas
3 hyperkeratotic cutaneous capillary-venous malformations(HCCVM)
4 segmental facial hemangiomas
5 Tufted angiomas

Answer 25

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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Question 26

Which of the following conditions is inherited in an X-linked dominant (XD) manner?
1 Chodrodysplasia punctata
2 CHILD Syndrome
3 Focal dermal hypoplasia
4 All of the answers are correct
5 None of the answers are correct

Answer 26

All of the syndromes listed are XD. Other XD syndromes are: Incontinentia pigmenti and Bazex syndrome.
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Question 27

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?
1 Sporadic
2 Autosomal dominant
3 Autosomal recessive
4 X-linked dominant
5 X-linked recessive

Answer 27

Maffucci syndrome is inherited in a sporadic manner.
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Question 28

Most common malignancy to develop in a patient with tricholemmomas, acral verrucous papules and cobble-stoning of buccal and gingival mucosa?
1 Thyroid cancer
2 Breast cancer
3 Colon cancer
4 Lymphoma
5 Melanoma

Answer 28

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. Breast cancer is the most common cancer to arise while thyroid carcinoma is the second most common.
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Question 29

Which of the following are cutaneous features of Marfan syndrome?
1 Loose skin and crumpled ears
2 Dermatofibrosis lenticularis and striae
3 Fat herniation and cutaneous atrophy
4 Sclerodermoid changes and dyspigmentation
5 Striae and elastosis perforans serpiginosa

Answer 29

Marfan syndrome is an autosomal dominant disorder caused by mutations in fibrillin 1 and 2. Patients have tall stature, arachnodactyly, pectus excavatum, high-arched palate, joint laxity, ectopia lentis with upward dislocation, dilated aorta with rupture, mitral valve prolapse, striae, and elastosis perforans serpiginosa.
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Question 30

Which of the following is caused by a defect in cathepsin C?
1 Rubenstein-Taybi
2 Bullous Icthyosis of Siemens
3 Muir-Torre
4 Papillon-Lefevre
5 Nail-Patella syndrome

Answer 30

Papillon-Lefevre is a palmoplantar keratoderma caused by a mutation in chromosome 11q14, leading to a defect in Cathepsin C, a lysosomal enzyme. Clinical manifestations of papillon lefevre include sharply demarcated palmoplantar keratoderma with extension to dorsal surface (transgrediens), spare hair, periodontitis, and pyoderma.
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Question 31

The most common cutaneous neoplasm associated with Muir Torre Syndrome is:
1 Sebaceous carcinoma
2 Sebaceous adenoma
3 Keratoacanthoma
4 Basal cell carcinoma with sebaceous differentiation
5 Squamous cell carcinomas

Answer 31

Muir-Torre syndrome is an autosomal dominant disorder due to a DNA mismatch repair gene (MSH2). Patients present with sebaceous tumors, with adenomas being the most common (sebaceous carcinomas next common) and associated visceral malignancies such as colon cancer (most common).
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Question 32

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?
1 Rhabdomyosarcoma
2 Adrenocortical carcinoma
3 Lung carcinoma
4 Breast carcinoma
5 Leukemia

Answer 32

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.
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Question 33

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:
1 Sublamina densa
2 Stratum spinosum
3 Lamina lucida
4 Stratum basale
5 None of these answers are correct

Answer 33

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.
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Question 34

The following enzyme defect is most commonly seen in CHILD Syndrome.
1 3-beta-hydroxysteroid dehydrogenase
2 3-beta-hydroxysteroid isomerase
3 Aryl sulfatase E
4 NAD oxido reductase
5 DNA helicase

Answer 34

CHILD Syndrome is a X-linked dominant disorder characterized by unilateral ichthyosiform erythroderma, ipsilateral limb deformity, and ipsilateral organ hypoplasia. The most commom gene defect is NSDHL which encodes 3-beta hydroxysteroid dehydrogenase. EBP gene defects which encode 3-beta-hydroxysteroid isomerase have been described, however this is the usual defect in Conradi-Hunermann Syndrome. Aryl sulfatase E is mutated in X-linked recessive chondrodysplasia punctata.
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Question 35

Patients with x-linked icthyosis are more prone to getting which two malignancies?
1 Pancreatic and acute lymphocytic leukemia (ALL)
2 Pancreatic and acute myelogenous leukemia (AML)
3 Testicular and AML
4 Testicular and ALL
5 Renal cell and ALL

Answer 35

Patients with x-linked icthyosis have a 20% chance of having cryptorchidism and are more prone to both testicular cancer and acute lymphocytic leukemia.
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Question 36

A patient with colon cancer is diagnosed with Muir-Torre syndrome. Which of the following cutaneous lesions might the patient have?
1 Keratoacanthomas
2 Seborrheic keratoses
3 Tricholemmomas
4 Arsenical keratoses
5 Basal cell carcinomas

Answer 36

Muir-Torre syndrome is an autosomal dominant disease caused by mutations in MSH2 and MLH1, DNA mismatch repair genes. Clinically, patients have multiple sebaceous tumors (adenomas are most common), keratoacanthomas, and are at risk for adenocarcinoma of the colon.
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Question 37

In which of the following Genodermatoses would one find cutaneous hyperpigmentation, blue lunulae and Kayser-Fleishcher rings:
1 Marfan’s Disease
2 Hemochromatosis
3 Gaucher’s Disease
4 Wilson’s Disease
5 Osteogenesis Imperfecta

Answer 37

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.
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Question 38

A 50 year man presents with generalized metallic-grey hyperpigmentation. His past medical history includes diabetes, hepatomegaly and arrythmias. Laboratory tests should include:
1 Copper levels
2 Lead levels
3 Iron levels
4 Arsenic levels
5 Cyanide levels

Answer 38

Hemochromatosis is an autosomal recessive disease resulting in increased intestinal iron absorption and iron deposition in a variety of organs. Clinical features include generalized metallic-grey hyperpigmentation, koilonychia, sparse or absent hair, hepatomegaly, cardiac failure/arrhythmias, insulin-dependent diabetes, hypogonadism and polyarthritis
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Question 39

A patient presents with starfish keratoses, pseudoainhum, honeycombed PPK, and generalized ichthyosis. What is the most likely genetic defect?
1 Connexin 31
2 Connexin 26
3 Connexin 30
4 Loricrin
5 Connexin 33

Answer 39

The patient has Vohwinkel syndrome. This is an autosomal dominant syndrome with 2 clinical variants. The variant described above with generalized ichthyosis is due to a loricrin mutation. In the classic form with nonprogressive hearing loss connexin 26 is mutated.
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Question 40

In chronic granulomatous disease, the diagnosis is made by which of the following tests?
1 Assay for fumarate hydratase
2 Nitroblue tetrazolium reduction assay
3 Assay for sphingomyelinase
4 Skin biopsy
5 Assay for glucocerebrosidase

Answer 40

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.
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Question 41

A 3 year-old boy presents with the findings seen in the image. He also has thrombocytopenia with purpura and a history of recurrent pyogenic bacterial infections. What is the most likely diagnosis in this child?
1 Chronic Granulomatous disease
2 Wiskott-Aldrich syndrome
3 Hyper-IgE syndrome
4 Severe combined immunodeficiency
5 Leiner syndrome

Answer 41

The findings described are consistent with Wiskott-Aldrich syndrome. The characteristic triad can be simplified to the 3 P’s - Pruritus (atopic dermatitis), Purpura (thrombocytopenia leading to purpura and other bleeding) and pyogenic infections. The remaining options are related to Wiskott-Aldrich in that they all have immunodeficiency as a feature, but not the same spectrum of disease.
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Question 42

Dental enamel pits are seen in which of the following conditions?
1 Hypomelanosis of Ito
2 Letterer-Siwe disease
3 Tuberous sclerosis
4 Jackson Sertoli syndrome
5 Hyper-IgE syndrome

Answer 42

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.
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Question 43

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 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?

1 Testicular
2 Abdominal
3 Lymph node
4 Lung
5 Rectal

Answer 43

Testicular
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.

Question 44

Ichthyosiform erythroderma in lines of Blaschko, follicular atrophoderma, and stippled epiphyses are characteristic of which of the following disorders?
1 Refsum syndrome
2 Chondrodysplasia punctata
3 Erythrokeratodermia variabilis
4 Netherton syndrome
5 Sjogren-Larsson syndrome

Answer 44

Chondrodysplasia punctata
Chondrodysplasia punctata is a peroxisomal disorder caused by mutations in several genes that is associated with ichthyosiform erythroderma in lines of Blaschko, follicular atrophoderma, and stippled epiphyses.

Question 45

In a patient suspected of having multiple endocrine neoplasia type IIb, which lab test would be appropriate?
1 Calcitonin
2 Glucagon
3 Parathyroid hormone
4 Calcium
5 Cortisol

Answer 45

Calcitonin
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.

Question 46

You receive a hospital consult from the gastroenterology service for a 42-year old woman with esophageal cancer. They would like your opinion on the yellow, thickened areas on her palms and soles in areas of pressure. When you speak with her, she says that her father had similar problems and it runs in her family. Which of the following is defective?
1 TOC gene
2 Desmoplakin
3 Plakoglobin
4 Connexin 30.3
5 Connexin 31

Answer 46

TOC gene
This case describes Howell-Evans syndrome. This AD syndrome characteristically has a PPK in areas of pressure, oral leukoplakia and esophageal carcinomas. Desmoplakin is defective in Carvajal syndrome and plakoglobin in Naxos syndrome. Connexin 31 and 30.3 are linked to erythrokeratoderma variabilis, which includes a PPK, but not esophageal carcinoma.

Question 47

Sphenoid wing dysplasia is seen in:
1 Tuberous sclerosis
2 Tay Syndrome
3 Mafucci syndrome
4 NF-1
5 NF-2

Answer 47

NF-1
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.

Question 48

Low-cystine content in hair and nails may contribute to the phenotype seen in:
1 Wilson’s disease
2 Menke’s Kinky Hair syndrome
3 Tay Syndrome
4 Nethertons
5 Bjornstad

Answer 48

Tay Syndrome
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.

Question 49

Which of the following bony defect is found in CHILD syndrome?
1 Polyostotic fibrous dysplasia
2 Stippled epiphyses
3 Calcification of falx cerebri
4 Osteopoikilosis
5 Sphenoid wing dysplasia

Answer 49

Stippled epiphyses
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.

Question 50

Which eye findings would be expected in an individual with this disorder associated with atherosclerosis?
1 Dendritic corneal ulcerations
2 Salt and pepper retinitis pigmentosa
3 Ectopia lentis
4 Angoid streaks
5 Keratoconus

Answer 50

Angoid streaks
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.

Question 51

The diagnostic test for chronic granulomatous disease is:
1 Dimethylglyoxime test
2 Nitroblue tetrazolium reduction assay
3 Histamine skin test
4 Bone marrow biopsy
5 Potassium hydroxide

Answer 51

Nitroblue tetrazolium reduction assay
Chronic granulomatous disease is characterized by a defect in the ability to kill catalase positive organisms within phagocytic leukocytes. This results from a neutrophilic defect in the cytochrome found in the NADPH oxidative pathway responsible for a respiratory burst. The nitroblue tetrazolium (NBT) reduction assay demonstrates the leukocyes� ability to reduce the dye and produce a blue color change. Patients with chronic granulomatous disease are unable to reduce the dye.

Question 52

Which of the following is caused by a mutation in a gene which codes for steroid sulfatase?
1 Fabry disease
2 Lesch-nyhan disease
3 X-linked ichthyosis
4 Lamellar icthyosis
5 Chediak-Higashi

Answer 52

X-linked ichthyosis
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.

Question 53

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:
1 Stool samples
2 Fontanelle examination
3 Examination of palms and soles
4 Palpation of abdomen
5 Hearing test

Answer 53

Examination of palms and soles
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.

Question 54

A 2 year old girl presents with sunken eyes, large ears, microcephaly and a photodistributed eruption on her face. Eye exam reveals ‘salt and pepper’ retina. The gene responsible for this syndrome codes for a:
1 Transcription factor
2 Surface glycoprotein
3 Lysosomal protease
4 DNA helicase
5 Mismatch repair gene

Answer 54

DNA helicase
The patient described has Cockayne syndrome, an autosomal recessive disorder believed to be due to a mutation in either DNA helicase or defective nucleotide excision repair. UV irradiated cells have decreased DNA and RNA synthesis and increased chromosomal breaks. Clinical features include cachectic dwarfism with microcephaly, thin nose, large ears, photosensitive eruption, cataracts, salt & pepper retina, and diffuse demyelination.

Question 55

Which of the following is correct about nevoid basal cell carcinoma syndrome?
1 known as Gardner syndrome
2 autosomal recessive
3 multiple keratoacanthomas
4 calicification of the falx
5 odontogenic steatomas

Answer 55

calicification of the falx
Nevoid basal cell carcinoma syndrome, also known as Gorlin syndrome, is an autosomal dominant disease, with abnormalities in the PTCH gene. It presents with multiple basal cell cancers early in life, frontal bossing, hypertelorism, odontogenic keratocysts, and bifid ribs. The presence of intracranial calcification of the falx cerebri is characteristic.

Question 56

A patient presents with focal symmetric palmoplantar keratoderma, thickened, hyperkeratotic fingernails and toenails with a “pincer” appearance and frequent staph and candida paronychial infections, follicular hyperkeratosis of the knees and elbows and oral leukokeratosis. The patients mother and grandfather both have similar skin findings. What is the defect in PC type I?
1 Keratin 6a/16
2 Keratin 6b/17
3 Keratin 1/10
4 Keratin 2e/10
5 None of these options are correct

Answer 56

Keratin 6a/16
Keratin 6a/16 are defective in PC type I. K6b17 is defective in PC type II, K1/10 in Unna-Thost PPK and epidermolytic hyperkeratosis, K2e/10 in Ichthyosis bullosa of Siemens.

Question 57

Hyperextesible skin, gaping wounds, cigarette-paper scars, molluscoid pseudotumors, and calcified subcutaneous nodules are characteristic of which syndrome?
1 Marfan syndrome
2 Congenital contractural arachnodactyly
3 Ehlers-Danlos Syndrome
4 Cutis laxa
5 Pseudoxanthoma elasticum

Answer 57

Ehlers-Danlos Syndrome
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.

Question 58

Mosaic mutations in PTEN are seen in which of the following conditions?
1 Gardner syndrome
2 Proteus syndrome
3 Incontinentia pigmenti
4 Noonan syndrome
5 Beckwith-Wiederman syndrome

Answer 58

Proteus 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.

Question 59

In one variant of epidermolysis bullosa simplex, those affected have muscular dystrophy in addition to the skin findings. Which protein mutation has been linked to this finding?
1 Plakoglobin
2 Plakophilin
3 Plectin
4 Desmoglein
5 Desmocollin

Answer 59

Plectin
A plectin mutation is linked with this subtype of epidermolysis bullosa simplex.

Question 60

A patient with Crowe’s sign and an optic glioma has which of the following disorders?
1 Neurofibromatosis I
2 Neurofibromatosis II
3 Watson syndrome
4 Tuberous sclerosis
5 Lester iris syndrome

Answer 60

Neurofibromatosis I
The diagnostic criteria for neurofibromatosis I include meeting 2 or more of the following 7 criteria: (1) >5 cafe au lait macules (CALMs) that are >5mm in a prepubertal person or >15 mm in a postpubertal person, (2) >1 neurofibroma or 1 plexiform neurofibroma, (3) axillary/inguinal freckling (Crowe’s sign), (4) optic glioma, (5) >1 Lisch nodule (iris hamartoma), (6) sphenoid dysplasia, (7) 1st degree relative with neurofibromatosis I.

Question 61

What is the genetic defect of this autosomal dominant disorder?
1 PTEN
2 PTPN11
3 Calcium ATPase 2A2
4 Calcium ATPase 2C1
5 SPINK5

Answer 61

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.

Question 62

Which of the following is a potentially serious complication of the blue rubber bleb nevus syndrome?
1 Development of chondrosarcomas
2 Development of angiosarcomas
3 Gastrointestinal hemorrhage
4 Development of lymphedema
5 Development of fluid retention

Answer 62

Gastrointestinal hemorrhage
Blue rubber bleb nevus syndrome is characterized by multiple tender venous malformations of skin and gastrointestinal tract, which can lead to gastrointestinal bleeding.

Question 63

Which genetic disease is characterized by round opacities seen on radiographs of the long bones?
1 Buschke-Olendorf syndrome
2 Chondrodysplasia punctata
3 Netherton syndrome
4 Osteogenesis imperfecta
5 Focal dermal hypoplasia

Answer 63

Buschke-Olendorf syndrome
Buschke-Ollendorf syndrome is an autosomal dominant disorder with dermatofibrosis lenticularis disseminata (elastomas) and osteopoikilosis, or round opacities of the bones. It is caused by a defect in LEMD 3 (aka MAN1), which codes an inner nuclear membrane protein. Focal dermal hypoplasia can cause osteopathia striata; osteogenesis imperfecta can have bone fractures; and chondrodysplasia punctata can have stippled epiphyses.

Question 64

A 27 year old presents with some mildly itchy spots on his posterior neck. Biopsy reveals elastosis perforans serpiginosa. Other notable exam findings include tall stature, joint laxity, pectus excavatum, and a high-arched palate. Which gene is most likely mutated in this patient?
1 Fibrillin 1
2 Fibronectin
3 Collagen 5
4 ABCC6
5 Fibulin 4

Answer 64

Fibrillin 1
Marfan syndrome is an autosomal dominant disorder characterized by tall stature, arachnodactyly, pectus excavatum, high-arched palate, joint laxity, ectopia lentis, aortic dilatation, striae, and elastosis perforans serpiginosa. The syndrome is caused by a defect in fibrillin 1 or 2. Fibronectin is defected in Type 10 Ehlers-Danlos syndrome. Collagen 5 defects can cause Ehlers-Danlos types 1 or 2. ABCC6 is mutated in pseudoxanthoma elasticum. Cutis laxa is caused by defects in fibulin 4.

Question 65

An infant with doughy, redundant skin and short sparse hairs is likely to show which features on x-ray?
1 Metaphyseal widening in the long bones
2 Sphenoid wing dysplasia
3 Periosteal thickening
4 Osteopoikilosis
5 Stippled epiphyses

Answer 65

Metaphyseal widening in the long bones
The patient described has Menkes Kinky Hair syndrome, an X-linked recessive disease due to a defect in an intestinal copper transport protein. Clinical features include pili torti, short, brittle “steel-wool” hair, and spare eyelashes and sparse broken eyebrows. The skin is often hypopigmented with a soft, “doughy” consistency and redundancy. Musculoskeletal manifestations include metaphyseal widening with spurs in the long bones

Question 66

Which of the following mutations has been linked to an NF-1 like presentation?
1 SLURP-1
2 Plakophilin-1
3 SPRED-1
4 ALK-1
5 TSC-1

Answer 66

SPRED-1
SPRED-1 acts as a suppressor of the Ras/MAPK pathway, the same pathway involved in neurofibromatosis-1. Likewise, defects in SPRED1 are the cause of neurofibromatosis type 1-like syndrome, also known as Legius Syndrome. Legius Syndrome has the following characteristics: cafe au lait spots, axillary and inguinal freckling, learning disability, and macrocephaly; likewise patients can actually meet criteria for the clinical diagnosis of NF-1. Although Legius Syndrome has many overlapping features with NF1, neurofibromas, lisch nodules, and CNS tumors have not been reported. (Brems H, et al. Nat Gen 2007.)

Question 67

Lamellar ichthyosis is caused by mutations in which of the following genes?
1 Steroid sulfatase
2 Fatty aldehyde oxidoreductase
3 Phytanoyl coenzyme A hydroxylase deficiency
4 Arylsulfatase E
5 Transglutaminase

Question 68

Crumpled ears are associated with which disorder?
1 Ehlers-Danlos Syndrome
2 Marfan syndrome
3 Congenital contractural arachnodactyly
4 Cutis laxa
5 Buschke-Ollendorf syndrome

Answer 68

Congenital contractural arachnodactyly
Congenital contractural arachnodactyly is an autosomal dominant disorder caused by mutations in fibrillin 2. Affected patients have long limbs, arachnodactyly, scoliosis, and crumpled ears.

Question 69

What phenotype results from a low activity of double stranded RNA adenosine deaminase?
1 Waardenberg’s syndrome type 2
2 Piebaldism
3 Tietz syndrome
4 dyschromatosis symmetrica hereditaria
5 oculocutaneous albinism type 4

Answer 69

dyschromatosis symmetrica hereditaria
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.

Question 70

A double row of eyelashes is associated with:
1 Lymphedema-distichiasis syndrome
2 Cornelia de Lange syndrome
3 Rubinstein-Taybi syndrome
4 Russell-Silver syndrome
5 Hunters syndrome

Answer 70

Lymphedema-distichiasis syndrome
A double row of eyelashes is defined as distichiasis and is associated with the Lymphedema-distichiasis syndrome. This syndrome is transmitted in an autosomal dominant fashion and is related to a mutation in FOXC2. Findings include late onset lymphedema, distichiasis, corneal irritation, ectropion, webbed neck and congenital heart defects. The remaining syndromes do not include distichiasis as a feature.

Question 71

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?
1 Autosomal recessive
2 Autosomal dominant
3 X-linked recessive
4 X-linked dominant
5 Sporadic

Answer 71

Sporadic
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.

Question 72

Which of the following is true regarding tuberous sclerosis?
1 Confetti-like macules are typically present at birth
2 Facial angiofibromas are the most common cutaneous manifestation
3 Hypomelanotic macules (ash leaf spots) have a decreased number of melanocytes
4 Periungual fibromas are considered a major feature in the diagnosis of tuberous sclerosis
5 6 or more hypomelanotic macules (ash leaf spots) are considered a major feature in the diagnosis of tuberous sclerosis

Answer 72

Periungual fibromas are considered a major feature in the diagnosis of tuberous sclerosis
The earliest and most common cutaneous manifestation of tuberous sclerosis are hypomelanotic macules (ash leaf spots), typically presenting at birth or early infancy. 3 or more of these lesions are considered a major criteria in diagnosis. Melanocyte numbers are normal. Confetti-like macules, on the other hand, are usually not apparent until the second decade of life. Facial angiofibromas occur in approximately 75% of patients, and tend to become more prominent with age. Periungual fibromas are considered a major feature for diagnosis, usually presenting around puberty to early adulthood.

Question 73

Which of the following is NOT a characteristic skin finding in patients with Down Syndrome?
1 Syringomas
2 Elastosis perforans serpiginosa
3 Single palmar crease
4 Flat nipples
5 Small tongue

Answer 73

Small tongue
Down syndrome is caused by nondisjunction and results in trisomy 21. Clinical features include single palmar crease, flat nipples, increased nuchal skin folds, syringomas, elastosis perforans serpiginosa, xerosis, epicanthic folds of eyes, protruding scrotal tongue and fissured thickened lips.

Question 74

Ichthyosis linearis circumflexa is one of the findings seen in the syndrome caused by which of the following genes?
1 SPINK5
2 SLURP1
3 GJB2
4 LMX1B
5 CYLD

Answer 74

SPINK5
The SPINK5 gene encodes for LEKTI, a serine protease inhibitor important in the regulation of proteolysis in epithelia formation and keratinocyte terminal differentiation, is mutated in Netherton’s Syndrome. Other findings include: trichorrhexis invaginata (bamboo, ball and socket hair), atopic dermatitis, and anaphylaxis from food allergy. SLURP1 is mutated in Mal de Maleda, GJB2 in Vohwinkel’s syndrome, LMX1B in Nail-Patella syndrome, and CYLD in Familial Cylindromiasis.

Question 75

Naxos syndrome is characterized by a right sided cardiomyopathy, wooly hair, and keratoderma. The epidermal structure defective in Naxos syndrome is:
1 Desmoglein 1
2 Desmoglein 3
3 Plakoglobin
4 Desmoplakin
5 Keratin 1/10

Answer 75

Plakoglobin
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.

Question 76

Which of the following is not a feature of Cockayne syndrome?
1 Dwarfism
2 Salt and pepper retina
3 Increased sister chromatid exchange
4 Increased risk of skin cancer
5 Poikiloderma

Answer 76

Increased risk of skin cancer
Patients with Cockayne syndrome do not have an increased risk of skin cancer. All the other findings are associated with Cockayne syndrome, as well as photosensitivity, deafness, cataracts, and sunken facies. Increased chromatid exchange is also seen in Bloom syndrome, dyskeratosis congenita, and Fanconi’s anemia.

Question 77

A child presents with macroglossia, exopthalmos and gigantism. He has a history of omphalocele repair and has circular depressions on the rim of the posterior helices. Although this syndrome is most often transmitted in a sporadic manner, 15% of cases have defects in which gene?
1 KIP2
2 ATM
3 VHL
4 FLT4
5 FOXC2

Answer 77

KIP2
KIP2 can be mutated in 15% of cases of Beckwith-Wiedemann Syndrome. KIP2 is a cyclin-dependent kinase inhibitor gene which acts as a negative regulator of cell proliferation. These children have an increase risk of Wilms’ tumor and organomegaly. In addition to the circular ear depression, they can also have a linear earlobe crease. The remaining genes are mutated in other syndromes with vascular disorders as a component: ATM in ataxia telangectasia, VHL in Von Hippel-Lindau, FLT4 in Hereditary lymphedema and FOXC2 in Lymphedema-distichiasis syndrome.

Question 78

Adenosine deaminase deficiency is associated with which of the following disorders?
1 Wiskott Aldrich syndrome
2 Gout
3 Job syndrome
4 Xeroderma pigmentosum
5 Severe combined immunodeficiency

Answer 78

Severe combined immunodeficiency
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.

Question 79

Which of the following is caused by a defect in keratins 4 & 13?
1 White sponge nevus
2 Epidermolysis bullosa simplex
3 Epidermolysis bullosa simplex with myotonic dystrophy
4 Junctional EB with pyloric atresia
5 Clouston’s syndrome

Answer 79

White sponge nevus
White sponge nevus is caused by a defect in keratins 4 & 13. The remaining entities have the corresponding defects: EB simplex—keratins 5 & 14 EB simplex with myotonic dystrophy—plectin Junctional EB with pyloric atresia—Integrin a-6, b4 Clouston’s syndrome (hidrotic ectodermal dysplasia)—connexin 30.

Question 80

Which vascular disorder is characterized by facial vascular malformation and ipsilateral intracranial and retinal arteriovenous malformations(AVMs)?
1 Sturge-Weber syndome
2 PHACES
3 Encephalotrigeminal angiomatosis
4 Bonnet Dechaune Blanc syndrome
5 Von Lohuizen’s disease

Answer 80

Bonnet Dechaune Blanc syndrome
Bonnet Bechaune Blanc syndome, also know as Wyburn-Mason syndrome, is characterized by a facial vascular malformation and ipsilateral intracranial and retinal AVMs. Encephalotrigeminal angiomatosis is another name for Sturge-Weber. Von Lohuizen’s disease is another name for cutis marmorata telangiectatica congenita.

Question 81

The most common neoplasm seen in Maffucci Syndrome is:
1 Enchondromas
2 Angiosarcomas
3 Osteosarcomas
4 Lymphangiosarcomas
5 chondrosarcoma

Answer 81

Enchondromas
Maffucci syndrome comprises of superficial and deep venous malformations, enchondromas, and short stature. Enchondromas are the most common neoplasm, while chondrosarcomas are the most common malignancies.

Question 82

A sporadic syndrome affecting transcriptional coactivator CREB-binding protein is:
1 Rubinstein-Taybi syndrome
2 Cornelia de Lange syndrome
3 Nonne-Milroy disease
4 Maffucci syndrome
5 Blue rubber bleb nevus syndrome

Answer 82

Rubinstein-Taybi syndrome
Rubinstein-Taybi syndrome is caused by a sporadically transmitted defect in transcriptional coactivator CREB-binding protein. This gene is responsible for encoding a nuclear protein which acts as a co-activator of cAMP regulated gene expression. Findings of this syndrome include: capillary malformation, short stature, broad thumbs, craniofacial abnormalities including beaked nose, mental retardation, strabismus, congenital heart defects and cryptorchidism. The other listed conditions are not related to this defect.

Question 83

Which of the following signs is not a criteria for the diagnosis of Neurofibromatosis type I?
1 Bilateral vestibular schwannomas
2 Axillary freckling
3 Optic gliomas
4 Greater than 5 cafe-au-lait macules
5 Sphenoid dysplasia

Answer 83

Bilateral vestibular schwannomas
Bilateral vestibular schwannomas are related to type II neurofibromatosis. The remaining options are diagnostic criteria for NF-1.

Question 84

Cutaneous meningiomas have been associated with what syndrome?
1 Neurofibromatisis
2 Cowden
3 Neurocutaneous melanosis
4 Gorlin
5 Glomangiomatosis

Answer 84

Neurofibromatisis
Cutaneous meningiomas are sperated into 3 types. Type 1 are thought to be misplaced meningeal cells, or rudimentary mengioceles. Type II develop along the course of cranial nerves. Type III lesions represent cutaneous metastasis or an underlying primary meningioma. Cutaneous meningiomas have been associated with cranial developmental anomalies and in neurofibromatosis.

Question 85

The hair abnormality shown in the image is characteristic of which of the following diseases?
1 Naxos disease
2 Trichothiodystrophy
3 Bjornstad syndrome
4 Monilethrix
5 All of the options are correct

Answer 85

Trichothiodystrophy
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.

Question 86

A patient with thyroid carcinoma and cobblestone-like changes of the oral mucosa will also likely have:
1 Trichoepitheliomas
2 Fibrofolliculomas
3 Tricholemmomas
4 Cylindromas
5 Syringomas

Answer 86

Tricholemmomas
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.

Question 87

Which type of epidermolysis bullosa is associated with mitten deformities of the hands?
1 Dominant dystrophic
2 Recessive dystrophic
3 Weber-Cockayne
4 Herlitz type
5 Generalized atrophic benign epidermolysis bullosa
(GABEB)

Answer 87

Recessive dystrophic
The recessive dystrophic type of epidermolysis bullosa is associated with chronic hand ulcers resulting in scarring that causes mitten deformities. These chronic scars often result in the formation of fatal squamous cell carcinomas.

Question 88

A 11 year-old female patient with hypoparathyroidism is referred to your clinic secondary to chronic mucocutanous candidiasis which is refractory to standard treatments. The patient also has malabsorption and severe chronic diarrhea. You determine that she has autoimmune polyendocrinopathy-candiasis-ectodermal dystrophy syndrome(APECED). Since only two of three major criteria are needed to make this diagnosis, this patient having demonstrated hypoparathyroidism and chronic mucocutanous candidiasis is diagnosed with APECED. What is the third major criteria that would qualify a patient to meet the diagnosis of APECED?
1 Ectodermal dysplasia
2 Insulin dependent diabetes mellitus
3 Chronic autoimmune hepatitis
4 Addison’s disease
5 Hypothyroidism

Answer 88

Addison’s disease
This patient has APECED, also know as autoimmune polyendocrinopathy syndrome type 1(APS type 1). Two of three major criteria are needed to make this diagnosis - chronic mucocutaneous candidiasis, hypoparathyroidism and Addison’s disease. They usually present within the first 5 years of life with chronic mucocutaneous candidiasis, then before the age of ten with hypoparathyroidism, and finally in early adulthood with Addison’s disease. They often present with chronic diarrhea and malabsorption. Ectodermal dysplasia usually does not present until the fifth decade. Autoimmune skin disease, such as vitiligo and alopecia areata are not uncommon.

Question 89

Which of the following immunoglobulins is commonly decreased in Wiskott-Aldrich syndrome?
1 IgA
2 IgD
3 IgE
4 IgM
5 IgG

Answer 89

IgM
IgM is decreased in WAS. IgA, IgD and IgE levels are all elevated. IgG is not abnormal in WAS.

Question 90

A patient with this autosomal recessive disorder caused by a defect in helicase is an increased risk for which malignancy?
1 Acute leukemia
2 Renal cell carcinoma
3 Medullary thyroid carcinoma
4 Squamous cell carcinoma of the lung
5 Prostate carcinoma

Answer 90

Acute leukemia
Bloom’s syndrome is an autosomal recessive disorder caused by a mutation in DNA helicase. It is characterized by photodistributed erythema in a butterfly distribution, malar hypoplasia with a prominent nose, high pitched voice, and an increased risk for malignancy (acute leukemia, lymphoma, and GI adenocarcinoma.)

Question 91

egarding the inheritance of Ehlers-Danlos syndrome, which subtype is inherited in an X-linked recessive manner?
1 The type with the lysyl oxidase deficiency
2 The type with the lysyl hydroxylase deficiency
3 The type with a collagen 5 defect
4 The type with a collagen 3 defect
5 The type with a defect in procollagen aminopeptidase

Answer 91

The type with the lysyl oxidase deficiency
Lysyl oxidase deficiency is related to type V or X-linked Ehlers-Danlos syndrome (EDS). Type IX, also has x-linked recessive inheritance with mild symptoms of EDS with occipital exostoses and hernias. Lysyl hydroxylase deficiency is seen in type VI EDS, linked with severe kyphoscoliosis, retinal detachment and other eye abnormalities. Collagen V deficiencies are seen in type I (Gravis) and type II (Mitis) EDS, associated with skin elasticity, gaping wounds, hypermobile joints, Gorlin�s sign, blue sclera and mitral valve prolapse.

Question 92

Angioid streaks on retinal exam are characteristic of which of the following syndromes?
1 Pseudoxanthoma elasticum
2 Choroid malformations
3 Eyelid papillomas
4 Lester iris
5 Salt & pepper retinitis pigmentosa

Answer 92

Pseudoxanthoma elasticum
Angioid streaks are characteristic of pseudoxanthoma elasticum. They are caused by rupture of Bruch’s membrane of the choroid. Choroid malformations are found in Sturge-Weber syndrome, eyelid papillomas in xeroderma pigmentosum, Lester iris in Nail-patella syndrome and salt & pepper retinitis pigmentosa in Refsum syndrome.

Question 93

Papillon-Lefevre and Haim-Munk syndromes have which of the following symptoms?
1 Right-ventricular cardiomyopathy
2 Pseudoainhum
3 Esophageal cancer
4 Eccrine syringofibradenoma
5 Periodontitis with tooth loss

Answer 93

Periodontitis with tooth loss
Right-ventricular cardiomyopathy is associated with Naxos syndrome, pseudoainhum is associated with Vohwinkel syndrome, esophageal cancer is associated with Howel-Evans syndrome, and eccrine syringofibradenomas are associated with Schopf-Schulz-Passarge syndrome. Periodontitis with tooth loss is associated with Papillon-Lefevre and Haim-Munk syndromes, which are caused by mutations in Cathepsin C.

Question 94

Retinal hemangioblastomas are found in which syndrome:
1 Osler-Weber-Rendu disease
2 Von-Hippel Lindau disease
3 Kasabach-Merritt syndrome
4 Klippel-Trenaunay Weber syndrome
5 Sturge-Weber syndrome

Answer 94

Von-Hippel Lindau 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.

Question 95

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’ Griscelli syndrome?
1 Giant lysosomal granules are present in neutrophils in the blood smear
2 Griscelli syndrome does not have albinism as a feature
3 Griscelli syndrome has no changes in hair color
4 All of these answers are correct
5 None of these answers are correct

Answer 95

Giant lysosomal granules are present in neutrophils in the blood smear
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.

Question 96

Which of the following conditions is inherited in an X-linked recessive manner?
1 Epidermolysis bullosa simplex
2 Ichthyosis vulgaris
3 Sjogren-Larsson syndrome
4 Wiskott-Aldrich Syndrome
5 Netherton’s Syndrome

Answer 96

Wiskott-Aldrich Syndrome
Wiskott-Aldrich Syndrome is inherited in an X-linked recessive manner. Epidermolysis bullosa simplex and ichthyosis vulgaris are inherited in an autosomal dominant (AD) manner. Sjogren-Larsson and Netherton’s syndrome are inherited in an autosomal recessive manner.

Question 97

An infant girl of short stature and shortened 4th and 5th metacarpals is being evaluated for coarctation of the aorta and horseshoe kidneys. Physical examination most likely reveals:
1 Webbed neck
2 Alopecia
3 Hemangioma
4 Giant congenital melanocytic nevus
5 Arachnodactyly

Answer 97

Webbed neck
Turner’s syndrome results from nondysjunction during gametogeneiss leading to the XO genotype. Clinical features include short stature, redundant neck folds/webbed neck, multiple pigmented nevi, low set hairline, triangular facies, low-set ears, ptosis, wide-set nipples, shortened 4th and 5th metacarpals, hypoplasia of lymphatics, coarctation of the aorta, and horseshoe kidneys.

Question 98

A 5 month old girl presents with failure to thrive. She has had life-long atopic dermatitis treated with topical hydrocortisone cream and has persisent hypernatremia. On your exam, she has generalized erythema and scaling of her body and trichorrhexis invaginata on examination of hairs from her eyebrows. Which syndrome is she most likely to have?
1 Leiner syndrome
2 Omenn Syndrome
3 Netherton Syndrome
4 Wiskott-Aldrich Syndrome
5 Severe atopic dermatitis

Answer 98

Netherton Syndrome
Netherton syndrome is caused by a mutation in the SPINK5 gene, encoding LEKT1. This is a serine protease inhibitor which is important in downregulating inflammation. Early presentation is with failure to thrive, generalized erythema/scale, hypernatremia, and sparse hair with the characteristic finding of trichorrhexis invaginata. Pili torti and trichorrhexis nodosa also can be seen. Eyebrow hair is most commonly affected. Omenn syndrome is an autosomal recessive form of severe combined immunodeficiency (SCID) with findings of failure to thrive, erythroderma, scaling, chronic diarrhea, lymphadenopathy, and hepatosplenomegaly. Leiner syndrome can present with failure to thrive, immunodeficiency and seborrheic dermatitis. Wiskott-Aldrich syndrome is an x-linked recessive condition with mutations of the WAS gene. Presentation includes atopic dermatitis, thrombocytopenia, recurrent bacterial infection, lymphoreticular malignancy with non-Hodgkin’s lymphoma being the most common, and increased IgA, D and E. With the characteristic hair changes, atopic dermatitis alone is not the most likely diagnosis.

Question 99

A 7 year old girl with abnormally short hair has progressive seizures, lethargy, ataxia, and mental retardation. A blood test reveals elevated levels of ammonia. What is the affected gene?
1 Argininosuccinase
2 ATP7A
3 Ectodysplasin A
4 Connexin 30
5 p63

Answer 99

Argininosuccinase
Argininosuccinic aciduria is an autosomal recessive disorder caused by mutations in argininosuccinase. It is characterized by trichorrhexis nodosa, hyperammonemia, hepatomegaly and vomiting, seizures, lethargy, coma, ataxia, and mental retardation.

Question 100

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:
1 Glaucoma
2 Cataracts
3 Subcapsular lens displacement
4 Copper deposition
5 Macular degeneration

Answer 100

Cataracts
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.

Question 101

The gene defect in Griscelli Syndrome is:
1 Myosin Va or Rab27a
2 LYST or CHS1
3 P gene
4 TRP1
5 None of these answers are correct

Answer 101

Myosin Va or Rab27a
Myosin Va or Rab27a are defective in Griscelli syndrome, an AR syndrome with mild albinism, pancytopenia, immunodeficiency, neurologic symptoms and an accelerated phase similar to Chediak-Higashi syndrome. LYST/CHS1 is defective in Chediak-Higashi syndrome. The P-gene is mutated in oculocutaneous albinism type 2 and TRP in oculocutaneous albinism type 3.

Question 102

Osteopathia striata is seen in which of the following disorders?
1 Gaucher’s disease
2 Albright’s syndrome
3 Aplasia cutis congenita
4 Focal dermal hypoplasia
5 Scleroderma

Answer 102

Focal dermal hypoplasia
Focal dermal hypoplasia (Goltz syndrome) is an X-linked dominant disorder that is lethal in males. There is linear atrophy following Blaschko’s lines with areas of fat herniation with underlying osteopathia striata, which is radiologically characterized by linear bony hyperdensity. Other features include mucocutaneous papillomas and pits, alopecia, nail dystrophy, tooth abnormalities, and colobomas.

Question 103

A 15 year old male patient is seen for evaluation of a congenital nevus. As a part of the review of systems, it is discovered that he has recurrent joint dislocations. Multiple family members have a similar problem. What is the defective gene in Type 3 Ehlers-Danlos syndrome?
1 Collagen 3
2 Collagen 5
3 Lysyl oxidase
4 Collagen 2
5 PLOD gene

Answer 103

Collagen 3
Type 3 Ehlers-Danlos syndrome, or benign hypermobile Ehlers-Danlos syndrome, is a relatively mild form of EDS with recurrent joint dislocations. The syndrome is a result of defective collagen 3. Defective collagen 5 is seen in EDS types 1 and 2 (gravis and mitis, respectively). Lysyl oxidase deficiency is seen in Type 5 (x-linked). Collagen 2 mutations can lead to Type 7 (arthrochalasis multiplex congenita). The PLOD gene is involved in type 6 (ocular-scoliotic).

Question 104

Familial macular and lichen amyloidosis is a feature of which of the following conditions?
1 Sipple syndrome
2 Peutz-Jeghers syndrome
3 Marfan syndrome
4 Dyskeratosis congenita
5 Birt-Hogg-Dube syndrome

Answer 104

Sipple syndrome
 Sipple syndrome (MEN 2a) is caused by autosomal dominant mutations in the ret protooncogene. Patients develop parathyroid cancers, pheochromocytomas, and medullary cancer of the thyroid gland. Familial macular and lichen amyloidosis is also a feature of this syndrome.

Question 105

A teenage female presents with the complaint of “nail fungus”. On exam, she has triangular lunulae, palmoplantar hyperhidrosis, micronychia and an absent patella. Which of the following screening tests should you order first?
1 Urinalysis
2 CBC
3 Fasting lipids
4 Renal ultrasound
5 X-ray of the knees, elbows and pelvis

Answer 105

Urinalysis
Patients with nail-patella syndrome can have glomerulonephritis and renal dysplasia leading to renal failure. Screening with a urinalysis is a reasonable first test. If this is abnormal, referral for a renal ultrasound could be useful. Fasting lipids and a CBC are not indicated.

Question 106

A deficiency in sialophorin, a surface glycoprotein, is thought to play a role in which genetic disorder?
1 Wiskott-aldrich syndrome
2 Chediak-higashi syndrome
3 Werner syndrome
4 Bloom Syndrome
5 Cornelia de Lange syndrome

Answer 106

Wiskott-aldrich syndrome
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.

Question 107

Mucosal malignancy is a complication of:
1 Oral hairy leukoplakia
2 White sponge nevus
3 Dyskeratosis congenital
4 Chronic candidiasis
5 Focal epithelial hyperplasia

Answer 107

Dyskeratosis congenital
Dyskeratosis congenital, also called Zinsser-Engman-Cole syndrome, is an X-linked recessive genodermatosis caused by a mutation in DKC1. DKC1 encodes for dyskerin, which helps to maintain telomeres through the pseudouridylation of rRNA. Features of this condition include reticulate gray-brown hyperpigmentation, dystrophic nails, alopecia and Fanconi�s type pancytopenia. Patients may have premalignant leukoplakia which should be followed closely.

Question 108

A patient with multiple sebaceous adenomas should be screened with which of the following examinations?
1 Retinal examination
2 Laryngoscopy
3 Colonoscopy
4 MRI of the spine
5 Renal ultrasound

Answer 108

Colonoscopy
Muir-Torre syndrome is an autosomal dominant disorder caused by the HMSH2 and MLH1 DNA mismatch repair genes. Clinically, there are numerous sebaceous adenomas, epitheliomas and carcinomas and multiple keratoacanthomas associated with indolent colon and other visceral adenocarcinomas. Patients and first-degree relatives should be screened by colonoscopy as colonic adenocarcinomas may precede the development of cutaneous tumors.

Question 109

A patient with multiple lentigines and blue nevi may also have:
1 Deafness
2 Pulmonary valve stenosis
3 Atrial myxoma
4 Mental retardation
5 GI malignancy

Answer 109

Atrial myxoma
This patient may have a constellation of features associated with NAME syndrome, otherwise known as Carney complex or LAMB syndrome. This condition is inherited in an autosomal dominant pattern and is due to a defect in the PRKAR1A gene. This condition is characterized by the following features: blue Nevi, Atrial myxomas, cutaneous Myxomas, and Ephelides. In addition, testicular tumors are seen as well as sexual precocity. Finally, patients may have endocrine abnormalities including pigmented nodular adrenocorticoal disease and Cushing syndrome as well as pituitary adenomas. Deafness, pulmonary stenosis, GI malignancies, and mental retardation are not features of this condition.

Question 110

Which of the following subtypes of Ehlers-Danlos Syndrome (EDS) is associated with early demise?
1 Type 1 (Gravis)
2 Type 4 (Vascular)
3 Type 5 (X-linked)
4 Type 7 (Arthrochalasis multiplex congenita)
5 Type 10 (Fibronectin)

Answer 110

Type 4 (Vascular)
 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.

Question 111

Ehlers-Danlos Syndrome with congenital adrenal hyperplasia is caused by mutations affecting which of the following?
1 Lysyl hydroxylase
2 Collagen 5
3 Fibronectin
4 Lysyl oxidase
5 Tenascin-X

Answer 111

Tenascin-X
Ehlers-Danlos Syndrome type with congenital adrenal hyperplasia is caused by mutations in tenascin-X.

Question 112

Birt-Hogg-Dube syndrome is most strongly associated with which of the following malignancies?
1 Basal cell carcinoma
2 Medulloblastoma
3 Renal cell carcinoma
4 Trichoepithelial carcinoma
5 Eccrine syringofibroadenoma

Answer 112

Renal 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.

Question 113

Focal Dermal Hypoplasia (Goltz Syndrome) can differentiated from Incontinentia Pigmenti by
1 Type of inheritance
2 Presence of Linear lesions along the lines of Blaschko
3 Presence of blistering lesions
4 Hair and teeth abnormality
5 Eye and CNS abnormality

Answer 113

Presence of blistering lesions
Both Focal Dermal Hypoplasia (Goltz Syndrome) and Incontinentia Pigmenti are inherited as X linked dominant (lethal in males).And both can have lesions along the lines of Blaschko with many similarities in systemic involvement. Howevere, Incontinentia Pigmenti is differntiated from Focal Dermal Hypoplasia by presence of blistering lesions in addition to hyperkeratosis and hyperpigmentation.

Question 114

Mutations in calcium transporters cause which pair of diseases?
1 Erythrokeratodermia variabilis and progressive symmetric erythrokeratodermia
2 Lamellar ichthyosis and nonbullous congenital ichthyosiform erythroderma
3 Refsum syndrome and Sjogren-Larsson syndrome
4 Chondrodysplasia punctata and CHILD syndrome
5 Darier’s disease and Hailey-Hailey disease

Answer 114

Darier’s disease and Hailey-Hailey disease
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.

Question 115

The combination of painful palmoplantar keratoderma and pseudoherpetic keratitis is characteristic of which of the following syndromes?
1 Naxos syndrome
2 Vohwinkel syndrome
3 Richner-Hanhart syndrome
4 Howel-Evans syndrome
5 Schopf-Schulz-Passarge syndrome

Answer 115

Richner-Hanhart syndrome
Richner-Hanhart syndrome (tyrosenemia type II) is an autosomal recessive disorder caused by a deficiency in hepatic tyrosine aminotransferase. This disease is characterized by painful PPK, pseudoherpetic keratitis and blindness. Treatment is low-tyrosine/phenylalanine diet.

Question 116

What is the gene defect in this condition, which is also called Mendes da Costa syndrome?
1 Keratin 1 and 10
2 SPINK5
3 SLURP-1
4 Connexin 26
5 Connexin 31

Answer 116

Connexin 31
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.

Question 117

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?
1 Head CT
2 Thoracic CT
3 Hepatic ultrasound
4 Endoscopy
5 Knee films

Answer 117

Endoscopy
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.

Question 118

The gene defect in LEOPARD syndrome is:
1 PTPN11
2 PRKAR1A
3 KIP2
4 ATM
5 Neurofibromin

Answer 118

PTPN11
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.

Question 119

A patient has recurrent infections and is found to have a disorder of phagocytic cells from an inability of phagocytes to undergo the respiratory burst needed to kill certain types of bacteria and fungi. Carriers of this disease are also at risk for which condition?
1 Breast cancer
2 Vitiligo
3 Discoid lupus
4 Thyroid disease
5 Cataracts

Answer 119

Discoid lupus
This patient has chronic granulomatous disease characterized by dysfunctional phagocytic cells. The most common molecular defect in chronic granulomatous disease is a mutation in the gene encoding the b subunit of cytochrome b. Carriers have a significant incidence of discoid lupus erythematosus, photosensitivity, Raynaud’s phenomenon, and aphthous ulcers. Carriers of ataxia telangiectasia are at risk for breast cancer.

Question 120

Which ocular finding may be seen in a patient with this skin condition?
1 Comma-shaped corneal opacities
2 Retinitis pigmentosa
3 Congenital hypertrophy of the retinal pigmented
epithelium
4 Angioid streaks
5 Pingueculae

Answer 120

Angioid streaks
Pseudoxanthoma elasticum is caused by a defect in connective tissue. Angioid streaks develop when a rupture occurs in Bruch’s membrane.

Question 121

Which one of the following is the most common oncogenic virus in patients with epidermodysplasia verruciformis?
1 HPV-5
2 HPV-8
3 HPV-13
4 HPV-16
5 HPV-33

Answer 121

HPV-5
Epidermodysplasia verruciformis is a rare autosomal recessive disorder in which an impaired cellular immunity allows widespread infection with certain subtypes of the human papilloma virus (HPV). Some of these lesions have a tendency for malignant transformation, most commonly those verruca caused by HPV type 5.

Question 122

Which of the following syndromes is associated with cutis marmorata?
1 Netherton’s
2 Papillon-Lefevre syndrome
3 Hemansky-Pudlak syndrome
4 Maffucci syndrome
5 Cornelia de Lange syndrome

Answer 122

Cornelia de Lange 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 hands and feet. They have characteristic facies which include hirsutism on the forehead, trichomegaly, synophrys, anteverted nostrils, long philtrum, and low-set ears.

Question 123

A 13 year old girl has woolly hair, keratoderma of the soles, edema of the lower extremities, and swelling of the abdomen. A cardiac evaluation reveals right-sided cardiomyopathy. What is the most likely defective protein?
1 Plakoglobin
2 Plectin
3 Desmocollin
4 Desmoglein
5 Desmoplakin

Answer 123

Plakoglobin
Naxos disease is caused by a defect in the plakoglobin protein. It is characterized by woolly hair, keratoderma, and right-sided cardiomyopathy.

Question 124

The nucleotide excision DNA repair pathway is defective in which disease:
1 Bourneville’s disease
2 Severe combined deficiency syndrome
3 Griscelli syndrome
4 Xeroderma pigmentosa
5 Sjogren-Larssen syndrome

Answer 124

Xeroderma pigmentosa
The pathogensis of Xeroderma Pigmentosum shows mutations i genes encoding DNA repair enzymes, leading to defective DNA excision repair upon exposure to UV radiation. Severe combined deficiency syndrome-major defect in cell-mediated and humoral immunity; most lack antibody-dependent cellular cytotoxicity and natural killer cell function. The pathogensis for Griscelli Syndrome is a mutation in gene encoding for myosin Va or RAB27 a. Sjogren-Larsson Syndrome has mutations in the FALDH gene. Bourneville’s syndrome (AKA Tuberous Sclerosis) shows a mutation in either TSC1 ancoding hamartin or TSC2 encoding tuberin.

Question 125

Erythematous keratotic plaques of KID Syndrome most commonly occur in which location?
1 Face
2 Neck
3 Chest
4 Back
5 Abdomen

Answer 125

Face
The erythematous keratotic plaques of KID Syndome occur on face, extremities > trunk. KID Syndrome is characterized by keratitis, icthyosis, and deafness. It is inherited in an autosomal dominant fashion and caused by a mutation in the GJB2 gene which encodes connexin 26.

Question 126

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?
1 Type I families have an increase incidence of pulmonary arteriovenous fistulas
2 Type II families have an increased incidence of pulmonary arteriovenous fistulas
3 Type I families have an increased incidence of hepatic arteriovenous malformations
4 Type II families have a decreased incidence of hepatic arteriovenous malformations
5 None of the answers are correct

Answer 126

Type I families have an increase incidence of pulmonary arteriovenous fistulas
There is an increased incidence of pulmonary arteriovenous fistulas in HHT type I. Type II has an increased incidence of hepatic arteriovenous malformations.

Question 127

Which of the following syndromes demonstrate atrophoderma vermiculatum?
1 Tuzun Syndrome
2 ROMBO Syndrome
3 Nicolau-Balus Syndrome
4 Braun-Falco-Marghescu Syndrome
5 All of these answers are correct

Answer 127

All of these answers are correct
All of the listed syndromes include atrophoderma vermiculatum as part of their constellation of symptoms. Atrophoderma vermiculatum is characterized by honeycomb pattern of atrophic scars on the face. Tuzun Syndrome also has scrotal tongue. ROMBO has BCCs, milia, peripheral vasodilation, trichoepitheliomas. Nicolau-Balus has eruptive syringomas and milia. Braun-Falco-Marghescu has keratosis pilaris and palmoplantar hyperkeratosis.

Question 128

Epidermolysis bullosa simplex is caused by blistering in which structure?
1 Granular layer keratinocyte
2 Spinous layer keratinocyte
3 Basal layer keratinocyte
4 Lamina densa
5 Sublamina densa

Answer 128

Basal layer keratinocyte
Epidermolysis bullosa simplex is caused by mutations in keratin 5 and 14 resulting in bullae within basal cell keratinocytes.