201 - 328 Flashcards

Question

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 1

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. Q/Q(M)-477482 Report a Problem

Answer 2

All of the syndromes listed are XD. Other XD syndromes are: Incontinentia pigmenti and Bazex syndrome. Q/Q(M)-477708 Report a Problem

Answer 3

Maffucci syndrome is inherited in a sporadic manner. Q/Q(M)-477785 Report a Problem

Answer 4

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. Q/Q(M)-476533 Report a Problem

Answer 5

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. Q/Q(M)-474278 Report a Problem

Answer 6

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. Q/Q(M)-474022 Report a Problem

Answer 7

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). Q/Q(M)-474041 Report a Problem

Answer 8

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. Q/Q(M)-477233 Report a Problem

Answer 9

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. Q/Q(M)-477714 Report a Problem

Answer 10

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. Q/Q(M)-477876 Report a Problem

Answer 11

Patients with x-linked icthyosis have a 20% chance of having cryptorchidism and are more prone to both testicular cancer and acute lymphocytic leukemia. Q/Q(M)-477498 Report a Problem

Answer 12

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. Q/Q(M)-477363 Report a Problem

Answer 13

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. Q/Q(M)-478695 Report a Problem

Answer 14

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 Q/Q(M)-474027 Report a Problem

Answer 15

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. Q/Q(M)-478196 Report a Problem

Answer 16

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. Q/Q(M)-478038 Report a Problem

Answer 17

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. Q/Q(M)-478024 Report a Problem

Answer 18

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. Q/Q(M)-477739 Report a Problem

Answer 19

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.

Answer 20

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.

Answer 21

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.

Answer 22

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.

Answer 23

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.

Answer 24

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.

Answer 25

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.

Answer 26

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.

Answer 27

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 leukocyesï¿½ ability to reduce the dye and produce a blue color change. Patients with chronic granulomatous disease are unable to reduce the dye.

Answer 28

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.

Answer 29

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.

Answer 30

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.

Answer 31

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.

Answer 32

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.

Answer 33

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.

Answer 34

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.

Answer 35

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

Answer 36

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.

Answer 37

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.

Answer 38

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.

Answer 39

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.

Answer 40

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.

Answer 41

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

Answer 42

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.)

Answer 43

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.

Answer 44

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.

Answer 45

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.

Answer 46

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.

Answer 47

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.

Answer 48

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.

Answer 49

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.

Answer 50

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.

Answer 51

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.

Answer 52

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.

Answer 53

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.

Answer 54

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.

Answer 55

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.

Answer 56

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.

Answer 57

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.

Answer 58

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

Answer 59

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.

Answer 60

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.

Answer 61

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.

Answer 62

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.

Answer 63

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.

Answer 64

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

Answer 65

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.)

Answer 66

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.

Answer 67

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.

Answer 68

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.

Answer 69

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.

Answer 70

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.

Answer 71

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.

Answer 72

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.

Answer 73

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.

Answer 74

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.

Answer 75

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.

Answer 76

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.

Answer 77

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.

Answer 78

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).

Answer 79

``` 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. ```

Answer 80

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.

Answer 81

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.

Answer 82

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.

Answer 83

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.

Answer 84

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.

Answer 85

``` 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. ```

Answer 86

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

Answer 87

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.

Answer 88

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.

Answer 89

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.

Answer 90

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.

Answer 91

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.

Answer 92

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.

Answer 93

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.

Answer 94

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.

Answer 95

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

Answer 96

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.

Answer 97

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.

Answer 98

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

Answer 99

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.

Answer 100

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.

Answer 101

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.

Answer 102

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.

Answer 103

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

201 - 328 Flashcards

(128 cards)