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Question 1

A 16 month-old girl presents with patchy alopecia, whorled erythematous scaly eruption, and asymmetric limb shortening. What laboratory or radiologic test may aid in diagnosis?
1 Brain MRI
2 Alkaline phosphatase
3 Chest radiograph
4 Bone films
5 Complete blood count

Answer 1

Bone films
The patient has Conradi-Hunermann Syndrome. This is a X-linked dominant disorder characterized by ichthyosiform erythroderma in Blaschko’s lines in infancy which resolves with follicular atrophoderma, patchy alopecia, short stature, cataracts, scoliosis, assymetric limb shortening. Bone films will demonstrate stippled epiphyses. Ichthyosis and stippled epiphyses resolve after infancy.

Question 2

A patient with 20 nail dystrophy, steatocystoma multiplex and natal teeth likely has a mutation in the genes coding for:
1 Keratins 5
2 Laminin 5
3 Plakophilin 1
4 Keratins 6b & 17
5 Keratins 6 &16

Answer 2

Keratins 6b & 17
Pachyonychia congenital is an autosomal dominant condition with 20 nail dystrophy. The patient described has Type II (Jackson-Sertole) disease, which includes steatocystoma multiplex, natal teeth, multiple cysts, and micropthalmia, and is caused by mutations in keratins 6b& 17. Type I (Jadassohn-Lewandowsky) also includes focal symmetric PPK, follicular hyperkeratosis, oral leukokeratoses and is caused by mutations in keratins 6 &16. Type III includes the clinical features of type I + corneal leukokeratosis. Mutations in keratins 5&14 represents EB simplex, Laminin 5 mutation is seen in Junctional EB, and plakophilin 1 mutation is seen in ectodermal dysplasia with skin fragility.

Question 3

Which of the following is defective in Ehlers-Danlos syndrome (EDS) with congenital adrenal hyperplasia?
1 Tenascin-X
2 Lysyl oxidase
3 Lysyl hydroxylase
4 None of these answers are correct
5 All of these answers are correct

Answer 3

Tenascin-X
Tenascin-X defects are associated with EDS and with congenital adrenal hyperplasia. The phenotype is that of typical EDS with hyperextensible skin, hypermobile joints, and tissue fragility. Lysyl oxidase is defective in X-linked EDS (type V) and Occipital horn syndrome (type IX). Lysyl hydroxylase is defective in ocular-scoliotic (type VI) EDS.

Question 4

Which type of porphyria is associated with hyponatremia?
1 Acute intermittent porphyria
2 Porphyria cutanea tarda
3 Variegate porphyria
4 Hereditary coproporphyria
5 Erythropoietic protoporphyria

Answer 4

Acute intermittent porphyria
Acute intermittent porphyria can cause hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion.

Question 5

Hypoplasia of the breast can be seen in which disease?
1 Anhidrotic ectodermal dysplasia
2 Maffucci syndrome
3 Congenital syphilis
4 Marfan syndrome
5 Osteogenesis imperfecta

Answer 5

Anhidrotic ectodermal dysplasia
Anhidrotic ectodermal dysplasia is a X-linked recessive disease caused by mutations in ectodysplasin, a member of the tumor necrosis family. Patients may have dry skin with pigmentation periorbitally, hypohidrosis, sparse hair, hypo-anodontia, nail dystrophy, and frontal bossing, and saddle nose deformity. In addition to abnormalities of other ectodermally derived structures, the breast and nipple-areolar complex may be absent or hypoplastic.

Question 6

Which disease is found more commonly in mothers of patients with chronic granulomatous disease?
1 Sarcoidosis
2 Erythema nodosum
3 Churg-Straus disease
4 Wegener’s disease
5 Discoid lupus erythematous

Answer 6

Discoid lupus erythematous
Female carriers of chronic granulomatous disease have an increase incidence of discoid lupus, infections and apthous stomatitis.

Question 7

A patient presents with several light blue cyst-like lesions on the eyelid. They consult their list of problems and bring up plantar hyperkeratosis and dysplastic toenails. On oral exam, you note that they have both upper and lower dentures. The patient relates that after losing their “baby teeth”, only 3 teeth grew in their place. What syndrome does this person most likely have?
1 Schopf-Schulz-Passarge
2 Gardner syndrome
3 Hypohidrotic ectodermal dysplasia
4 Cowden syndrome
5 Cronkhite-Canada

Answer 7

Schopf-Schulz-Passarge
Schopf-Schulz-Passarge syndrome is associated with hydrocystomas of the eyelids, hypotrichosis (near complete loss of hair early in life), hypodontia, nail abnormalities and multiple palmoplantar eccrine syringofibroadenomas. The other listed syndromes do not fit the description above.

Question 8

A child presenting with the scalp findings shown and a right arm hypoplasia would be diagnosed with which of the following syndromes?
1 Adams-Oliver syndrome
2 Bart’s syndrome
3 Progeria
4 Dunnigan syndrome
5 None of these options are correct

Answer 8

Adams-Oliver syndrome
Adams-Oliver syndrome is defined by aplasia cutis congenita (ACC) (shown in the image), usually of the midline scalp with limb hypoplasia. Bart’s syndrome also has ACC as a finding, but it is usually present on the lower extremities and associated dominant dystrophic epidermolysis bullosa. Progeria is a premature aging syndrome associated with a lamin-A mutation. Dunnigan syndrome is also known as Familial partial lipodystrophy and is associated with a mutation in the BSCL2 gene. Neither are associated with findings of ACC.

Question 9

Which of the following findings is characteristic of a mutation in lamin A?
1 Lipoatrophic sclerodermoid skin
2 Alopecia
3 Craniomegaly with small face
4 Severe premature atherosclerosis with early death
5 All of the answers are correct

Answer 9

All of the answers are correct
A mutation in Lamin A causes Progeria (Hutchinson-Gilford syndrome). Other findings include nail atrophy and muscle/bone wasting. Presentation is in the first or second year of life. An increased urine hyaluronic acid can be helpful in diagnosis.

Question 10

What is the mode of transmission for lamellar ichthyosis?
1 Autosomal dominant
2 Autosomal recessive
3 X-linked dominant
4 X-linked recessive
5 Sporadic

Answer 10

Autosomal recessive
Lamellar ichthyosis which is characterized by collodian membrane in newborns and platelike scale in children and adults is an autosomal recessive syndrome. The gene defect is transglutaminase 1 (TGM1).

Think Transglutaminase Fetal Rat

Question 11

The most common cutaneous association with monilethrix is:
1 Eczema
2 Hypopigmentation
3 Hyperpigmentation
4 Keratosis Pilaris
5 Atrophy

Answer 11

Keratosis Pilaris
Monilethrix is an autosomal dominant condition which, by definition, presents with “beaded” hear. Clinically, patients present with short, sparse lusterless hair. Keratosis pilaris is the most common associated feature.

Question 12

Which type of epidermolysis bullosa simplex is associated with early death?
1 Weber-Cockayne
2 Generalized (Koebner)
3 Dowling-Maera
4 Ogna variant
5 Non-Herlitz variant

Answer 12

Dowling-Maera
The Dowling-Maera variant of epidermolysis bullosa simplex is associated with widespread bullae, significant mucous membrane and laryngeal/esophageal involvement, nail dystrophy, and early death.

Question 13

The arylsulfatase C gene is mutated in which disease?
1 X-linked ichthyosis
2 Refsum syndrome
3 Haim-Munk syndrome
4 Naxos syndrome
5 Griscelli syndrome

Answer 13

X-linked ichthyosis
Arylsulfatase C is also known as steroid sulfatase and is mutated in X-linked ichthyosis. This condition is inherited in a X-linked recessive pattern. Clinical findings include: brown scale sparing palms, soles and flexures, comma-shaped corneal opacities, failure of labor progression and cryptorchidism. It is also mutated in X-linked recessive type chondrodysplasia punctata.

Question 14

Premalignant leukoplakia of the oral mucosa is associated with:
1 Bloom syndrome
2 Werner Syndrome
3 Xeroderma Pigmentosum
4 Dyskeratosis Congenita
5 Rothmund-Thomson syndrome
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Answer 14

Dyskeratosis Congenita
 Dyskeratosis Congenita (also known as Zinsser-Engman-Cole syndrome) is thought to have two modes of inheritance. The more common X-linked disorder is due to a mutation in the Dyskerin gene, while the autosomal dominant form is due to a mutation in TERC, a telomerase RNA component. Clinical features include reticulated gray-brown hyperpigmentation, paloplantar hyperkeratosis, alopecia, onychodystrophy, premalignant leukoplakia of any mucosal surface, and mental retardation.

Question 15

Which cutaneous finding is seen in patients with phenylketonuria?
1 Angular stomatitis
2 Ichthyosis
3 Pigment dilution of hair and skin
4 Phyrnoderma
5 Erosive diaper dermatitis

What is the enzyme defect?

The accumulation of ally

What should the PKU patients avoid eating in their diet?

Answer 15

Pigment dilution of hair and skin
Phenylketonuria is an autosomal RECESSIVE condition caused by a mutation in the gene coding for phenylalanine hydroxylase**. Defect in this enzyme results in accumulation of phenylalanine and its metabolites. I_ncreased phenylalanine_** has toxic effects on the central nervous system in addition to competitively inhibiting tyrosine in melanogenesis. Inhibition of melanogenesis results in pigmentary dilution of the hair and skin. Other features of this condition include a predisposition to eczema, sclerodermoid changes of the skin, urine that has a distinctive “mousy” odor, psychomotor delay, mental retardation, seizures and hyperreflexia. A low-phenylalanine diet instituted early on can prevent these manifestations of the disease. The morbidity of phenylketonuria has improved since the advent of routine neonatal screening for this condition.

Phenylalanine ——-> Tyrosine —-> Melanin

+Phenylanine Hydroxylase

Phenyl Ketonuria (PKU) is a common metabolic disorder in growing children. A child suffering from PKU has defective legs and is usually unable to stand. Such a child may also be mentally retarded. This condition is due to a defect in the amino acid metabolism. In the course of amino acid metabolism there is a step in which the amino acid phenyl-alanine gets converted into another amino acid called tyrosine. This conversion requires specific enzyme called phenyl pyruvic hydroxylase. In the child suffering from PKU this particular enzyme will be absent and as a result phenyl-alanine gets converted into a ketone body phenyl pyruvic acid. It starts circulating throughout the body through the blood resulting in the disorder. The absence of the enzyme phenyl pyruvic hydroxylase is due to the expression of a recessive autosomal gene in the homozygous condition.

PKU can be detected by a simple urine test. Such children are usually treated with a diet, which is free from the amino acid phenyl-alanine.

Question 16

Which syndrome is characterized by hyperhidrosis, lack of pain sensation, hypersalivation, and absent fungiform papillae?
1 Turner Syndrome
2 Noonan Syndrome
3 Riley-Day
4 Rubinstein-Taybi syndrome
5 Cornelia de lange Syndrome

Answer 16

Riley-Day

“Riley Day the IRON CHEF cutting his fingers”

Riley-Day syndrome is also known as Familial Dysautonomia. It is an autosomal RECESSIVE disorder with the gene defect on the long arm of chromosome 9.

Patients have unmyelinated sensory and sympathetic neurons and autonomic dysfunction, leading to hyperhidrosis, decreased corneal sensation and tear flow, hypersalivation, gastroesophageal reflux, decreased deep tendon reflexes, and lack of pain sensation.

They also exhibit abnormal histamine skin test.

Question 17

Retention of primary teeth a dental finding of 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 17

Hyper-IgE syndrome
Hyper-Immunoglobulin E syndrome is an autosomal dominant condition with impaired regulation of IgE function and deficient neutrophil chemotaxis. There is increased susceptibilty to infections and increased IgE serum levels. Retained primary teeth and lack of development of secondary teeth are characteristic findings. The remaining conditions do not have this as a prominent finding.

Question 18

All of the following disorders are exacerbated by UV radiation and have the eye findings in photo except:
1 Bloom syndrome
2 Hartnup’s disease
3 Refsum syndrome
4 Cockayne syndrome
5 Rothmund-Thomopson syndrome

Answer 18

Refsum syndrome
Refsum’s syndrome is an autosomal recessive disorder caused by mutations in phytanoyl-CoA hydroxylase. Clinically, patients have mild icthyosis, cerebellar ataxia, polyneuropathy, salt and pepper retinitis pigmentosa, sensorineural deafness, and arrhythmias with heart block. They are not overly sensitive to UV radiation.

Question 19

Homocystinuria is caused by a defect in:
1 Phenylalanine hydroxylase
2 Biotinidase
3 Holocarboxylase synthetase
4 Cystathione beta-synthetase
5 Gp91-phox

What is the most common eye abnormailty?

Answer 19

Cystathione beta-synthetase
Cystathione beta-synthetase is defective in homocystinuria, an autosomal recessive conditions characterized by increased homocystine and methionine levels in blood and urine. Other findings include a malar flush, DVTs/emboli, cardiovascular disease, livedo reticularis, leg ulcers, blonde hair/fiar complexion, downward lens dislocation, glaucoma, mental retardation, seizures, psychiatric disorders and a marfanoid body habitus. The other enzymes are not involved in this condition.

Question 20

Cutaneous osteomas are seen in which syndrome?
1 Waardenburg syndrome
2 LEOPARD syndrome
3 Carney complex
4 Albright hereditary osteodystrophy
5 Gaucher�s syndrome

Answer 20

Albright hereditary osteodystrophy is caused by mutations in the Gs subunit of adenylate cyclase. There is calcification and ossification due to pseudohypoparathyroidism, absent 4th knuckle, and hypogonadism.
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Question 21

A child with phenylketonuria likely presents with which cutaneous problems?
1 Blue-gray generalized hyperpigmentation
2 Alopecia universalis
3 Generalized hypopigmentation
4 Generalized hyperpigmentation
5 Leg ulcers

Answer 21

Phenylketonuria is an autsomal recessive disorder caused by a mutation on the long arm of chromosome 12. A deficiency of phenylalanine hydroxylase or its cofactor tetrahydrobiopterin leads to accumulation of phenylalanine. Clinical features include generalized hypopigmentation, eczematous dermatitis, sclerodermoid changes, seizures, psychomotor delay, urine with �mousy� odor, mental retardation.
Q/Q(M)-474030 Report a Problem

Question 22

Patients with junctional epidermolysis bullosa have been found to have mutations in:
1 Laminin 5
2 Bullous pemphigoid antigen 2
3 Collagen 17
4 BP180
5 All of the answers are correct

Answer 22

All of the answers are correct. Laminin 5 is a protein integral in the adhesion of the dermis to the epidermis. Also involved in junctional epidermolysis bullosa is bullous pemphigoid antigen 2, collagen 17 and BP180, which are synonymous for the same structure.
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Question 23

Which genetic defect could explain cutaneous findings in addition to abnormal immunoglobulin levels, recurrent respiratory infections, hypogonadism, and an increased risk of leukemia and lymphoma?
1 RecQL3
2 ERCC6
3 WAS gene
4 NADPH oxidase
5 Adenosine deaminase

Answer 23

Bloom’s syndrome is an autosomal recessive disorder caused by mutations in the RecQL3 gene encoding a DNA helicase. Clinically, individuals with Bloom’s syndrome have a photodistributed erythema with telangectasia on the malar eminences.

The may also have decreased IgM and IgA levels, hypogonadism**, and an increased risk for **leukemia and lymphoma.

Question 24

What is the underlying gene defect for this transgrediens form of palmoplanter keratoderma
1 SLURP-1
2 TOC gene
3 Plakoglobin
4 Keratin type 1
5 Keratin type 9

Answer 24

Attached picture is Mal de Meleda (keratosis palmoplantaris transgrediens) which is an autosomal recessive form of diffuse PPK, associated with keratotic plaques that extend to the dorsal aspects of the hands and feet (“transgrediens”) and may overlie joints . Hyperhidrosis, superinfection, and occasionally perioral erythema, brachydactyly, and nail abnormalities are associated. Mal de Meleda is due to mutations in ARSB, which encodes SLURP-1. The other choices represent gene defects for “non-transgrediens” forms of PPK (Plakoglobin in Naxos syndrome, TOC gene in Howel-Evans syndrome, K1 in non-epidermolytic PPK “Unna-Thost”, and K9 in epidermolytic PPK “Vorner”

Question 25

A child presents with pretibial hyperpigmentation, ataxia, decreased motor coordination, cirrhosis, and decreased motor coordination. The physical exam which would reveal the most specific finding for this disease is: 1 Hearing test 2 Slit-lamp eye exam 3 EKG 4 Colonoscopy 5 Renal ultrasound

Answer 25

Wilson's disease (also known as hepatolenticular degeneration) is an autosomal recessive disorder result in defective biliary excretion of copper, leading to copper accumulation in the liver, brain and cornea. Clinical features include hepatomegaly, cirrhosis, ataxia, dysarthria, decreased motor coordination, pretibial hyperpigmentation, blue lunulae, and copper deposition in the cornea�Kayser-Fleisher ring, which can be diagnosed using a slit-lamp. Q/Q(M)-474029 Report a Problem

Question 26

Nevoid basal carcinoma syndrome (Gorlin syndrome) is autosomal dominant transmitted mutation of the patched gene. Symptoms include innumberable basal cell carcinomas, painful odontogenic jaw keratocysts, palmoplantar pits, frontal bossing, bifid ribs and what other bony abnormality? 1 Polyostotic fibrous dysplasia 2 Stippled epiphyses 3 Calcification of falx cerebri 4 Osteopoikilosis 5 Sphenoid wing dysplasia

Answer 26

Calcification of falx cerebri is seen in Gorlin's syndrome. CHILD syndrome and chondrodysplasia punctata both can exhibit stippled epiphyses. Polyostotic fibrous dysplasia is found in McCune-Albright syndrome, osteopoikilosis in seen in Buschke-Ollendorf syndrome. Sphenoid wing dysplasia is seen in neurofibromatosis type I.

Question 27

A Puerto Rican woman is seen in clinic for a pruritic rash on her trunk. A punch biopsy is performed. The biopsy site continues to bleed, with hematoma formation. The bleeding is eventually controlled. On further exam, her skin and hair are light brown. She has a history of granulomatous colitis. What it the most likely reason she had excess bleeding with a simple procedure? 1 Her platelets lack dense bodies, causing excess bleeding 2 Her intrinsic factor is deficient 3 Her Factor VIII levels are low 4 She is congentially deficient in platelets 5 None of the answers are correct

Answer 27

Platelets without dense bodies cause excess bleeding in Hermansky-Pudlak syndrome. Other features of this condition include oculocutaneous albinism, ceroid lysosomal storage disease resulting in pulmonary fibrosis, granulomatous colitis.

Question 28

A patient with port wine stain on a lower extremity, hemihypertrophy of the limb and lymphatic and deep venouse insufficiency of the affected limb would be considered to have Klippel-Trenaunay-Weber syndrome. What additional feature would need to be present to define the patient as having Parkes-Weber syndrome? 1 Arteriovenous fistulas 2 Multiple cafe-au-lait macules 3 Macroglossia 4 Cutis marmorata 5 Distichiasis

Answer 28

Parkes-Weber syndrome has the additional feature of arteriovenous fistulas. The remaining features are not part of these syndromes.

Question 29

Which of the following diseases is caused by a mutation in a gap junction protein? 1 Striated PPK 2 Schopf-Schulz-Passarge syndrome 3 Mal de Meleda 4 Vohwinkel syndrome (classic) 5 Vohwinkel syndrome (ichthyotic)

Answer 29

Classic Vohwinkel syndrome is caused by mutations in connexin 26, a gap junction protein. Ichthyotic Vohwinkel syndrome is caused by mutations in loricrin and has ichthyosis but not deafness.

Question 30

A patient with Bloom Syndrome is most likely to have which laboratory abnormalities: 1 Decreased immunoglobulins 2 Macrocytic anemia 3 Elevated IgE 4 Thrombocytopenia 5 Positive ANA

Answer 30

Decreased immunoglobulins Bloom syndrome is an autosomal recessive disorder due to a mutation in the BLM gene which codes for a DNA helicase. Patients have impaired DNA repair after UV exposure and increased photosensitivity. Clinical features include photodistributed erythema, cheilitis, high-pitched voice, hypogonadism, and increased risk for leukemia, lymphoma and GI adenocarcinoma. Laboratory evaluation reveals decreased IgA, IgM and IgG leading to increased risk of respiratory infections

Question 31

Which of the following features is not associated with Cornelia de Lange Syndrome? 1 Normal intelligence 2 Characteristic facies with downturned mouth, hirsutism, synophrys, trichomegaly, anteverted nostrils, long philtrum and low set ears 3 Cryptorchidism 4 Fifth finger clinodactyly 5 Recurrent lung infections

Answer 31

Normal intelligence Children with Cornelia de Lange are usually severly retarded with an IQ \<35. In addition to the features listed above, other features include cutis marmorata, hypoplastic nipples and umbilicus, low-pitched cry in infancy and congenital heart defects. While most cases are inherited in a sporadic manner, those cases which are familial are thought to be autosomal dominant and associated with the NIPBL (nipped-beta-like) gene. Prognosis is poor with premature death often secondary to sspiration or recurrent pulmonary infection.

Question 32

Defects in Fibrillin 2 are linked with: 1 Congenital contractural arachnodactyly 2 Cutis Laxa 3 Arthrochalasis multiplex congenita 4 Occipital horn syndrome 5 Lipoid proteinosis

Answer 32

Fibrillin 2 defects arelinked primarily with congenital contractural arachnodactyly. This syndrome is associated with long limbs, arachnodactyly, scoliosis and crumpled ears. Occasionally, fibrillin 2 can be associated with Marfan syndrome also. The other conditions are not linked to fibrillin mutations.

Question 33

The finding of 'maltese crosses' in the urine is characteristic of which of the following conditions? 1 Alkaptonuria 2 Fabry disease 3 Gaucher disease 4 Neimann-Pick disease 5 Hunter syndrome

Answer 33

The 'maltese cross' finding in urine is characteristic of Fabry disease. Alkaptonuria will show dark urine with a pH \> 7.0. There are no urinary findings in Hunter syndrome, Gaucher or Neimann-Pick disease.

Question 34

A 12 year-old boy with pits on his palms and lateral fingers may have: 1 Arsenic exposure 2 A hereditary keratoderma 3 A corynebacteria infection 4 An inherited cancer syndrome 5 Secondary syphilis

Answer 34

Basal cell nevus syndrome is an autosomal dominant disease caused by mutations in the PTCH1 gene. Clinically, patients may have numerous basal cell carcinomas, palmoplantar pits, jaw cysts, frontal bossing, bifid ribs, calcification of falx cerebri, medulloblastoma, ovarian fibromas and fibrosarcomas.

Question 35

The characteristic dental findings in patients with tuberous sclerosis are: 1 Peg teeth 2 Anodontia 3 Enamel pits 4 Odontogenic cysts 5 Retention of primary teeth

Answer 35

Enamel pits are the characteristic dental findings in tuberous sclerosis. Peg teeth are found in incontinentia pigmenti and anhidrotic ectodermal dysplasia. Anodontia is found in hypomelanosis of ito and incontinentia pigmenti. Odontogenic cysts are seen in Gorlin syndrome, and retention of primary teeth is characteristic of Job syndrome.

Question 36

What is the classic radiologic findings associated with this disorder? 1 Dural calcifications 2 Calcifications of the falx-cerebri 3 Tram-track calcifications of the temporal and occipital cortex 4 Osteopatha striata 5 Osteopoikilosis

Answer 36

Sturge-Weber syndrome is a sporadic disroder characterized by a facial capillary malformation in a trigeminal nerve distribution. Patients with Sturge-Weber may have cerebral atrophy, ipsilateral vascular malformations of the leptomeninges, seizures, and glaucoma. The classic radiologic finding is tram-track calcifications of the temporal and occipital cortex.

Question 37

On cutaneous exam, angiokeratoma corporis diffusum is characteristic of which of the following conditions? 1 Sialodosis 2 Fucosidosis 3 Fabry disease 4 All of these options are correct 5 None of these options are correct

Answer 37

Findings of angiokeratoma corporis diffusum are found in all three listed conditions. They cannot by distinguished by skin exam.

Question 38

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 38

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.

Question 39

Tyrosinase positive albinism (oculocutaneous albinism type 2) is caused by a mutation in which of the following: 1 Tyrosinase 2 P gene 3 Tyrosinase related protein 1 4 C-kit 5 NEMO

Answer 39

P gene Oculocutaneous albinism (OCA) type 1 (Tyrosinase negative albinism) is caused by mutations in the tyrosinase gene. OCA type 2 (tyrosinase positive albinism) is caused by mutations in the P gene. OCA type 3 is caused by mutations in the tyrosinase related protein 1 gene. C-kit mutations cause piebaldism and NEMO mutations cause incontinentia pigmenti.

Question 40

Underlying defect for the disease shown in picture is 1 ATP2A2 2 ATP2C1 3 BPAG1 4 BPAG2 5 Collagen type 17

Answer 40

ATP2C1 The disease shown in image is Hailey-Hailey disease (Familial Benign Pemphigus) which is an autosomal dominant genodermatosis, caused by mutation in ATP2C1, encoding a calcium pump protein related to SERCA2. It is characterized by recurrent vesicles and erosions, which most commonly appear on the sides and back of the neck, in the axillae, in the groin, and in the perianal regions. The disorder is not seen before puberty and usually has its onset in the late teens or early 20s. In the intertriginous area lesions tend to form erythematous plaques with dry crusting and soft, flat, and moist granular vegetations. Burning or pruritus is common, and, particularly in the intertriginous areas, lesions tend to become irritating, painful, and exceedingly uncomfortable. ATP2A2 is underlying defect in Darier's disease, other choices are defects seen in pemphigoid and epidermolysis bullosa. Q/Q(M)-482120 Report a Problem

Question 41

Which of the following eye findings is caused by the rupture of Bruch's membrane? 1 Angioid streaks 2 Blue sclerae 3 Retinal detachment 4 Ruptured globe 5 Keratoconus

Answer 41

The rupture of Bruch's membrane causes angioid streaks in pseudoxanthoma elasticum. Bruch's membrane is the innermost layer of choroid with a central layer of elastic fibers. The other findings are found in Ehlers-Danlos syndrome and are not related to Bruch's membrane.

Question 42

Pruritus is Sjogren Larsson syndrome is attributed to accumulation of what molecule(s)? 1 Bile salts 2 Histamine 3 Leukotriene 4 All of these answers are correct 5 None of these answers are correct

Answer 42

Accumulation of leukotriene B4 contributes to pruritus in Sjogren Larsson syndrome. Leukotriene inhibitors may be helpful in controlling symptoms.

Question 43

A patient with hypohydrosis and hyperpyrexia, anodontia, and sparse hair has which syndrome: 1 Dyskeratosis congenita 2 Pachyonychia congenita 3 Anhidrotic ectodermal dysplasia 4 Hidrotic ectodermal dysplasia 5 Papillon Lefevre

Answer 43

Anhidrotic ectodermal dysplasia is an x-linked recessive disorder which presents with the triad of hypohydrosis (or anhidrosis) with hyperpyrexia, anodontia (other dental findings include peg teeth, molars with hooked cusps) and sparse hair. Patients tend to overheat.

Question 44

Mutations in nuclear lamins are associated with which clinical feature? 1 Lipomatosis 2 Sarcomas 3 Lymphedema 4 Aplasia cutis congenita 5 Lipodystrophy

Answer 44

Bernardinelli-Seip congenital lipodystrophy and familial partial lipodystrophy are caused by mutations in nuclear lamins. The former is characterized by generalized lipodystrophy and the latter is characterized by by partial lipodystrophy.

Question 45

Which opthamologic disease is associated with this disorder? 1 Glaucoma 2 Ectopia lentis 3 Cataracts 4 Posterior subcasular lentiular opacity 5 Retinitis pigmentosa

Answer 45

Glaucoma Sturge-Weber syndrome is a sporadic disease characterized by a capillary malformation in the trigeminal distribution. Patients may have associated cerebral atrophy, vascular malformations of the leptomeninges, and seizures. All patients with Sturge-Weber should be referred to the opthamologist for glaucoma screening.

Question 46

Mucosal neuromas, pheochromocytoma and medullary thyroid carcinoma in a patient with a marfanoid body habitus is associated with which of the following gene defects? 1 Menin 2 RET proto-oncogene 3 PTEN 4 BHD 5 STK11

Answer 46

The RET proto-oncogene is mutated in Multiple Endocrine Neoplasia type II. Type IIb is described above. Other findings include rare parathyroid abnormalities, megacolon, thickened lips and thick, everted upper eyelids. Menin is associated with MEN type I, PTEN with Cowden disease, BHD with Birt-Hogg-Dube syndrome and STK11 with Peutz-Jeghers syndrome.

Question 47

Which of the following is caused by a mutation in a gene that leads to defective NF-KB activation? 1 MEN IIa 2 Piebaldism 3 Chediak-Higashi 4 Vohwinkel�s 5 Incontinentia pigmenti

Answer 47

Incontinential pigmenti is an X-linked dominant disorder caused by a mutation in the NEMO gene located at Xq28. NEMO is an NF-KB modulator. A genetic defect in NEMO leads to defective activation of NF-KB (a transcription factor). MEN IIa is caused by a mutation in the RET proto-oncogene, piebaldism is caused by the C-kit protocogene, chediak-higashi is caused by a mutation in lysosomal tracking, and Vohwinkel�s is caused by a defect in the loricrin gene, which codes for a structural protein.

Question 48

A patient with Klinefelter Syndrome may be expected to experience which of the following: 1 Recurrent pulmonary infections 2 Recurrent leg ulcers 3 Pulmonary valve stenosis 4 Gastroesophageal reflux 5 Scarring alopecia

Answer 48

Klinefelter syndrome results from nondisjunction during meiosis, leading to the XXY genotype. Patients are characteristically tall (long lower extremities) with scant body and pubic hair. Klinefelter patients have numerous varicosities predisposing them to recurrent leg ulcers.

Question 49

A 5 year old boy is being seen by neurology for seizures and by ENT for a hoarse voice. He is referred to dermatology for evaluation of verrucous nodules of the elbows and knees. While reviewing his chart, it is noted that he has calcifications in the hippocampus seen on imaging. What is the most likely diagnosis of this patient? 1 Lipoid proteinosis 2 Psoriasis 3 Severe combined immunodeficiency disorder 4 Poland syndrome 5 Vohwinkel syndrome

Answer 49

Lipoid proteinosis is an autosomal recessive disorder caused by defects in the extracellular matrix protein 1 gene. It is characterized by scars and yellow papules of the face and oropharynx, yellowish papules on the eyelid margin, hoarse voice, verrucous nodules of the elbows and knees, and calcification of the temporal lobe and hippocampus with occasional seizures.

Question 50

The presence of natal teeth and pincer nails suggests which disease entity? 1 Congenital syphillis 2 Thalidomide exposure in utero 3 Incontinentia pigmenti 4 Pachyonychia congenita 5 Anhidrotic ectodermal dysplasia

Answer 50

Pachyonychia congentia is an autosomal dominant condition characterized by a constellation of findings affecting ectodermal structures. These include the presence of natal teeth, steatocystoma multiplex, follicular hyperkeratosis of the knees, elbows and extensor extremities, eruptive vellus hair cysts, and oral leukokeratosis which is not pre-malignant. In addition, nail findings include twenty-nail dystrophy, subungual hyperkeratosis with increase transverse curvature ("pincer nails") and candidal paronychia. There are two forms of pachyonychia congenital: Type 1 (Jadassohn-Lewandowsky syndrome) caused by defects in keratin 6a and 16, and Type 2 (Jackson-Lawler type) caused by defects in keratins 6b and 17. Anhidrotic ectodermal dysplasia is associated with peg-shaped teeth, hypoanodontia, and a non-specific nail dystrophy. Likewise, incontientia pigmenti also is characterized by anodontia and peg-shaped teeth and dystrophic changes of the nail. Finally congenital syphilis is a well-recognized cause of pegged teeth. Limb deformities are the most serious sequelae of thalidomide exposure in utero.

Question 51

What is the gene defect in harlequin fetus? 1 Transglutaminase 2 Steroid sulfatse 3 ABCA12 4 ABCC6 5 None of these answers are correct

Answer 51

Harlequin fetus is an autosomal recessive disorder. The gene defect is ABCA12.

Question 52

What is the gene defect in harlequin fetus? 1 Transglutaminase 2 Steroid sulfatse 3 ABCA12 4 ABCC6 5 None of these answers are correct

Answer 52

Harlequin fetus is an autosomal recessive disorder. The gene defect is ABCA12.

Question 53

Spastic ditetraplegia is associated with which of the following disorders? 1 Sjogren-Larsson syndrome 2 X-linked ichthyosis 3 Lamellar ichthyosis 4 KID syndrome 5 Refsum syndrome

Answer 53

Sjogren-Larsson syndrome is an autosomal recessive disorder caused by mutations in the fatty aldehyde oxidoreductase/alcohol dehydrogenase gene. This disorder is characterized by ichthyosis, spastic ditetraplegia, mental retardation, epilepsy, glistening dot retinal pigmentation, and dental enamel dysplasia.

Question 54

A patient with myotonic dystrophy and multiple skin lesions most likely has activating mutations in which of the following? 1 Beta-catenin 2 Desmoplakin 3 Plakoglobin 4 Desmoglein 5 Alpha 6-beta 4 integrin

Answer 54

Myotonic dystrophy with multiple pilomatricomas is described above. Activating mutations in Beta-catenin are found in this syndrome. The other listed options are desmosomal proteins and are not involved in this syndrome.

Question 55

Mutations affecting the VEGF receptor-3 cause which of the following disorders? 1 Hereditary lymphedema (Nonne-Milroy disease) 2 Lymphedema-distichiasis syndrome 3 Lymphedema and ptosis 4 Noonan syndrome 5 Hereditary hemorrhagic telangiectasias

Answer 55

Hereditary lymphedema (Nonne-Milroy disease) is an autosomal dominant condition caused by mutations in the FLT4 gene which encodes for VEGF receptor-3. There is congenital lymphedema and chylous ascites, scrotal swelling, intestinal tract protein loss, persistent bilateral pleural effusion, and hypoproteinemia.

Question 56

What protein is deficient in the condition shown? 1 Calcium ATP�ase IIC1 2 Calcium ATP�ase IIA2 3 PEX-7 4 SPINK5 5 Desmoglein 3

Answer 56

The picture shown is Hailey-Hailey disease. This is an autosomally dominant condition with a defect in Calcium ATP�ase IIC1. On H&E stain, an acantholytic �dilapidated brick wall� appearance is seen. Calcium ATP�ase IIA2 is defective in Darier�s Disease, PEX-7 in autosomal recessive type Conradi-Hunermann disease, SPINK5 in Netherton�s disease and Desmoglein 3 in pemphigus vulgaris.

Question 57

A patient Buschke-Ollendorff syndrome has osteopoikilosis and which cutaneous finding? 1 Waxy papules along the eyelids 2 Caf� au lait macules 3 Port wine stain 4 Juvenile elastoma 5 Epidermal nevi

Answer 57

Juvenile elastoma Buschke-Ollendorf syndrome is an autosomal dominant syndrome associated with increased elastic fiber in the skin. Key features include dermatofibrosis lenticularis disseminata (also called juvenile elastomas) and osteopoikilosis.

Question 58

Which of the following metals is deficient in the serum of patients with Menkes kinky hair syndrome? 1 Copper 2 Iron 3 Selenium 4 Zinc 5 Biotin

Answer 58

Menkes kinky hair syndrome is transmitted in an X-linked recessive manner and is caused by a mutation in ATP7A, an ATP-dependent copper tranporter. This defect results in low serum levels of copper. These individuals will have hair abnormalities such as sparse, hypopigmented brittle hair, eyelashes and eyebrows, lax skin, a "cupid's bow" upper lip, CNS progressive deterioration, seizures, skeletal abnormalities and tortuous arteries. The other listed items are not associated with Menkes syndrome.

Question 59

A patient with renal cell carcinoma caused by mutations in fumarate hydratase deficiency likely suffers which of the following conditions? 1 Von-Hippel-Lindau syndrome 2 Cowden syndrome 3 Birt-Hogg-Dube syndrome 4 Familial multiple cutaneous leiomyomatosis 5 Multiple endocrine neoplasia

Answer 59

Familial multiple cutaneous leiomyomatosis Familial multiple cutaneous leiomyomatosis is an autosomal dominant condition caused by mutations in the fumarate hydratase gene. Clinically, there are multiple cutaneous leiomyomas, uterine leiomyomas and leiomyosarcomas, as well as renal cell carcinomas.

Question 60

Which finding would you expect in a child with dyskeratosis congenita? 1 Increased risk for pancreatic cancers 2 Oral leukoplakia 3 Hirsutism 4 Normal hematologic status 5 Normal nails

Answer 60

Mild to moderate mental retardation occurs in up to 50% of cases. A Fanconi-type pancytopenia may occur resulting in early death. These children have alopecia, not hirsutism, along with nail dystrophy. There is an increased risk for development of premalignant oral leukoplakia, not pancreatic malignancy.

Question 61

Which syndrome is characterized by broad thumbs, a large beaked nose, and capillary malformation? 1 Klinefelter 2 Proteus syndrome 3 Bloom syndrome 4 Rubinstein-Taybi 5 Ehlers-Danlos syndrome

Answer 61

Rubinstein-Taybi syndrome has been associated with a deletion localized to the short arm of chromosome 16. Patients are severely retarded with strabismus, crytorchidism, and congenital heart defects. They have a characteristic beaked nose with nasal septum below alae accompanied by a broad nasal bridge, downslanting palpebral fissures, and broad thumbs and halluces.

Question 62

What medication may exacerbate this autosomally dominant, acnatholytic disorder? 1 Phenytoin 2 Lithium 3 Oral contraceptives 4 Anti-malarials 5 Corticosteroids

Answer 62

Lithium Darier's disease is autosomal dominant condition characterized by hyperkeratotic papules coalescing into warty plaques and cobblestoned papules on mucosal surfaces. The cutaneous manifestations may be exacerbated by lithium.

Question 63

Anodontia is a bone finding 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 63

Hypomelanosis of Ito, or Incontinentia pigmenti achromians is a condition characterized by marble-cake hypopigmentation, epilepsy, alopecia, scoliosis and mental/motor retardation. The characteristic dental abnormality is anodontia. The remaining syndromes are not associated with anodontia.

Question 64

In patients with diffuse congenital hemangiomatosis, the most common site for extracutaneous involvement is the : 1 Liver 2 Thyroid 3 Lungs 4 Colon 5 Brain

Answer 64

Diffuse congenital hemangiomatosis is characterized by multiple hemangiomas with the **_liver_** being the most common extracutaneous site, followed by the lungs. Liver hemangioma may be complicated by hepatomegaly, obstructive jaundice, and portal hypertension.

Question 65

You are consulted on a patient with possible Nethertons Syndrome. Which location of the body would most likely have hairs demonstrating trichorrhexis invaginata? 1 Scalp 2 Eyebrow 3 Eyelash 4 All of these answers are correct 5 None of these answers are correct

Answer 65

Eyebrow hair is most common site with hairs demonstrating trichorrhexis invaginata.

Question 66

Dermatofibrosis lenticularis disseminata is seen in which of the following conditions? 1 Ehlers-Danlos syndrome 2 Marfan syndrome 3 Pseudoxanthoma elasticum 4 Focal dermal hypoplasia 5 Buschke-Ollendorf syndrome

Answer 66

Buschke-Ollendorf syndrome is an autosomal dominant disorder characterized by dermatofibrosis lenticularis disseminata (cutaneous elastomas distributed symmetrically over the buttocks, trunk and proximal extremities), and **_osteopoikilosis_** (round opacities in bones).

Question 67

An infant presents with multiple congenital hemangomas in an generalized distribution. What is the most serious associated condition? 1 Congestive Heart Failure 2 Obstructive jaundice 3 Portal hypertension 4 All of the answers are correct 5 None of the answers are correct

Answer 67

Congestive Heart Failure High output congestive heart failure can lead to death in these children. Obstructive jaundice and portal hypertension both occur, but are less likely to cause death. The hemangiomas will undergo spontaneous regression.

Question 68

Patients with Chondrodysplasia punctata can have findings of stippled epiphyses on X-ray examination. Which other x-linked dominant condition can have stippled epiphyses? 1 CHILD syndrome 2 Incontinentia Pigmenti 3 Focal Dermal Hypoplasia 4 Goltz syndrome 5 Bazex syndrome

Answer 68

CHILD syndrome All of the syndromes listed have X-linked dominant inheritance. CHILD syndome also has findings of stippled epiphyses. Incontinentia pigmenti is caused by defecdts in the NEMO gene. Findings include peg/conical teeth, eye and CNS defects and alopecia. There are no bone abnormalities. Focal Dermal Hypoplasia, otherwise known as Goltz syndrome has findings of linear atrophy following Blaschko's lines with areas of fat herniation, mucocutaneous papillomas and pits, alopecia, nail dystrophy, tooth abnormalities and osteopathia striata (striations of the long bones). Bazex syndrome is associated with follicular atrophoderma, hypohidrosis, hypotrichosis and multiple basal cell carcinomas. There are no bone abnormalities associated.

Question 69

Yellow-brown depositions in Descemet's membrane of the corneas is diagnostic for: 1 Hemochromatosis 2 Neurofibromatosis 3 Hepatolenticular degeneration 4 Pseudoxanthoma elasticum 5 Diabetes mellitus

Answer 69

Hepatolenticular degeneration Hepatolenticular degeneration or Wilson Disease is caused by a defect in biliary excretion of copper leading to accumulation in the liver, brain, cornea, pretibial hyperpigmentation, hepatomegaly and cirrhosis. The Kayser-Fleischer ring is the yellow-brown copper deposition in Descemet's membrane of the cornea. Other findings include ataxia, dysarthria and dementia. Hemochromatosis does not have an eye finding. Neurofibromatosis has Lisch nodules and Pseudoxanthoma elasticum has angioid streaks of the retina.

Question 70

Which keratins are expressed in the suprabasal palmoplantar epidermis? 1 Keratins 1 and 9 2 Keratins 1 and 10 3 Keratins 4 and 13 4 Keratins 5 and 14 5 Keratins 8 and 18

Answer 70

Keratins are expressed in pairs of acidic and basic keratins and are tissue- and differentiation-specific. Keratins 1 and 9 are expressed in the suprabasal palmoplantar epidermis, keratins 1 and 10 in suprabasal nonpalmoplantar epidermis, keratins 2e and 10 in the granular layer, keratins 4 and 13 in mucosal epithelium, keratins 5 and 14 in the basal layer, and keratins 8 and 18 in simple epithelium.

Question 71

"Mousy" odor of urine is characteristic of which of the following syndromes? 1 Phenylketonuria 2 Hunter disease 3 Alkaptonuria 4 Maple Syrup Urine disease 5 Hurler disease

Answer 71

Phenylketonuria will cause a "mousy" odor in the urine. Patients with Alkaptonuria will have black urine. Maple syrup urine disease will have a sweet odor. Hunter/Hurler diseases are not associated with urinary issues.

Question 72

Findings of milia, cylindromas and the condition shown in the pathology image are characteristic of which of the following syndromes? 1 Gorlin's syndrome 2 Familial cylindromatosis 3 Brook-Spiegler syndrome 4 Rasmusen syndrome 5 Rombo syndrome

Answer 72

Brook-Spiegler syndrome Brooke-Spiegler syndrome is an uncommon disease with a predisposition to develop cutaneous adnexal neoplasms such as cylindromas, trichoepitheliomas, spiradenomas, trichoblastomas, basal-cell carcinomas, follicular cysts, organoid nevi, and malignant transformation of pre-existing tumors in the affected individuals.

Question 73

A middle-aged woman complains of multiple rough lesions on her trunk. Biopsy reveals connective tissue nevi. Because other family members have had similar lesions, genetic testing is performed, revealing a defect in the LEMD3 gene. What is the classic bone finding in patients with a defective LEMD3 gene? 1 Osteopoikilosis 2 Osteopathia striata 3 Tibial bowing 4 Lumbar ankylosis 5 Frequent fractures of the long bones

Answer 73

Buschkeâ Ollendorff syndrome is a rare genetic syndrome characterized by multiple connective tissue nevi and osteopoikilosis. Osteopoikilosis is dysplasia of bone leading to the presence of multiple bone islands in the skeleton. The defective gene is LEMD3. Osteopathia striata is associated with focal dermal hypoplasia. Tibial bowing is seen in rickets. Lumbar ankylosis is found in ankylosing spondylitis. Frequent fractures of long bones is seen in osteogenesis imperfecta.

Question 74

What nail change is seen in patients with Mal de Meleda Syndrome? 1 Onycholysis 2 Longitudinal ridging 3 Koilonychia 4 leukonychia 5 pterygium

Answer 74

Koilonychia Mal de Meleda is an autosomal recessive disease characterized by transgedient malodorous PPK, hyperhidrosis, keratotic plaques at knees and elbows, subungual hyperkeratosis, and koilonychia. The gene defect is SLURP 1. Meleda Puzzle SLURP-1

Question 75

The most common cardiovascular defect in patients with Noonan syndrome is: 1 Atrial septal defect 2 Ventricular septal defect 3 Enlarged aorta 4 Pulmonic valve stenosis 5 Aortic stenosis

Answer 75

Noonan's syndrome is also known as cardiofaciocutaneous syndrome. Patients have short stature, ptosis, hypertelorism, low-set ears, thick lips and curly hair. Pulmonic valve stenosis is the most common cardiovascular defect, with atrial septal defects also seen. It is type of dwarfism, a genetic disorder (hereditary) that prevents normal development or causes abnormal development of various parts of the body. Referred as an autosomal dominant condition, this defect affects genes; which are responsible for individual’s growth.Some symptoms of the disease are mild mental retardation, **_unusual chest shape**_, delayed puberty and _**short neck._** Current 7 genes are known that can cause this disorder and the main cause is mutation in those genes. There is no specific cure known for this disease. Treatment depends upon the stage and type of the disease. Growth hormones can be way out for the short stature. **_Hypertelorism_**, derived from the Greek word "telouros" (meaning distant), is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits (eyes)--orbital hypertelorism. In this condition the distance between the inner eye corners as well as the distance between the pupils is greater than normal. Hypertelorism should not be confused with telecanthus, in which the distance between the inner eye corners is increased but that of the outer eye corners remains unchanged.[1] Therefore the distance between the pupils is normal.

Question 76

Dermatofibrosis lenticularis disseminata and osteopoikilosis are findings seen with mutations of which of the following genes? 1 LEMD3 2 Fibrillin 2 3 ABCC6 4 Lysyl hydroxylase 5 Lysyl oxidase What stain will confirm the diagnosis of dermatofibrosis lenticularis disseminata?

Answer 76

Buschke-Ollendorf syndrome is caused by a loss-of-function mutation in LEMD3. Stains with Elastic fibers = Verhoeff-van Gieson Dermatofibrosis lenticularis disseminata are small papules or discs of increased dermal elastic tissue appearing in early life; when osteopoikilosis is also present, the condition is called osteodermatopoikilosis or Buschke-Ollendorf syndrome; autosomal dominant inheritance. (05 Mar 2000) The radiographic appearance of osteopoikilosis on an x-ray is characterized by a pattern of numerous white densities of similar size spread throughout all the bones. This is a systemic condition. It must be differentiated from blastic metastasis, which can also present radiographically as white densities interspersed throughout bone. Blastic metastasis tends to present with larger and more irregular densities in less of a uniform pattern. Another differentiating factor is age, with blastic metastasis mostly affecting older people, and osteopoikilosis being found in people 20 years of age and younger.

Question 77

Which malignancy is seen in approximately 15-20% of people with the disease characterized by a defect in a parathyroid hormone receptor protein? 1 Osteosarcoma 2 Angiosarcoma 3 Chondrosarcoma 4 Rhabdomyosarcoma 5 Epitheliod sarcoma

Answer 77

Approximately 15-20% of patients with Maffucci's syndrome will develop chondrosarcoma. Maffucci's syndrome is due to a defect in a parathyroid hormone receptor protein.

Question 78

Ivory-colored papules between the angles of the scapulae are characteristic of which syndrome: 1 Hurler 2 Scheie 3 Morquio 4 Hunter 5 Sanfilippo

Answer 78

These syndromes are all mucopolysaccharidoses. These papules are characteristic of Hunter syndrome which is caused by a deficiency in iduronate sulfatase. Hunter syndrome, or mucopolysaccharidosis Type II, is a lysosomal storage disease caused by a deficient (or absent) enzyme, iduronate-2-sulfatase (I2S).[1][2] The accumulated substrate in Hunter's syndrome is heparan sulfate and dermatan sulfate.[3] The syndrome has X-linked recessive inheritance.[3] PathophysiologyHunter syndrome, or mucopolysaccharidosis II (MPS II), is a serious genetic disorder that primarily affects males (X-linked recessive). It interferes with the body's ability to break down and recycle specific mucopolysaccharides, also known as glycosaminoglycans or GAG. Hunter syndrome is one of several related lysosomal storage diseases. In Hunter syndrome, GAG builds up in cells throughout the body due to a deficiency or absence of the enzyme iduronate-2-sulfatase (I2S). This buildup interferes with the way certain cells and organs in the body function and leads to a number of serious symptoms. As the buildup of GAG continues throughout the cells of the body, signs of Hunter syndrome become more visible. Physical manifestations for some people with Hunter syndrome include distinct facial features and large head. In some cases of Hunter syndrome, central nervous system involvement leads to developmental delays and nervous system problems. Not all people with Hunter syndrome are affected by the disease in exactly the same way, and the rate of symptom progression varies widely. However, Hunter syndrome is always severe, progressive, and life-limiting. Signs and symptomsThe symptoms of Hunter syndrome (MPS II) are generally not apparent at birth, but usually start to become noticeable after the first year of life. Often, the first symptoms of Hunter syndrome may include abdominal hernias, ear infections, runny noses, and colds. Since these symptoms are quite common among all infants, they are not likely to lead a doctor to make a diagnosis of Hunter syndrome right away. As the buildup of GAG continues throughout the cells of the body, signs of Hunter syndrome become more visible. Physical appearances of many children with Hunter syndrome include a distinctive coarseness in their facial features, including a prominent forehead, a nose with a flattened bridge, and an enlarged tongue. For this reason, unrelated children with Hunter syndrome often look alike. They may also have a large head as well as an enlarged abdomen. Many continue to have frequent infections of the ears and respiratory tract. The continued storage of GAG in cells can lead to organs being affected in important ways. The thickening of the heart valves along with the walls of the heart can result in progressive decline in cardiac function. The walls of the airway may become thickened as well, leading to breathing problems while sleeping (obstructive airway disease). People with Hunter syndrome may also have limited lung capacity due to pulmonary involvement. As the liver and spleen grow larger with time, the belly may become distended, making hernias more noticeable. All major joints (including the wrists, elbows, shoulders, hips, and knees) may be affected by Hunter syndrome, leading to joint stiffness and limited motion. Progressive involvement of the finger and thumb joints results in decreased ability to pick up small objects. The effects on other joints, such as hips and knees, can make it increasingly difficult to walk normally. If carpal tunnel syndrome develops, a further decrease in hand function can occur. The bones themselves may be affected, resulting in short stature. **_In addition, pebbly, ivory-colored skin lesions**_ may be found on the _**upper arms and legs and upper back_** of some people with Hunter syndrome. The presence or absence of the skin lesions is not helpful, however, in predicting clinical severity in Hunter syndrome. Finally, the storage of GAG in the brain can lead to delayed development with subsequent mental retardation. The rate and degree of progression may be different for each person with Hunter syndrome. There is a broad range of severity in the symptoms of Hunter syndrome. It is important to note that though the term "mild" is used by physicians in comparing people with Hunter syndrome, the effects of even mild disease are quite serious. Two of the most significant areas of variability concern the degree of mental retardation and expected lifespan. Some people who have Hunter syndrome are not mentally retarded and live into their 20s or 30s; there are occasional reports of people who have lived into their 50s or 60s. The quality of life remains high in a large number of people, and many adults are actively employed.[citation needed] In contrast, others with Hunter syndrome develop severe mental impairment and have life expectancies of 15 years or fewer.

Question 79

A 16 year-old girl presents with a family history of Gardner syndrome. Her mother is very concerned that her daughter may have the syndrome as it runs in her family and she has many skin complaints. What is likelihood that this girl has Gardner syndrome based on what you now about the inheritance pattern and the fact that her father is unaffected and her mother is a heterozygote for this condition? 1 50% 2 25% 3 10% 4 75% 5 90%

Answer 79

Her mother is a heterozygote for the condition and her father is homozygous as a non-carrier. Gardner syndrome is passed in an autosomal dominant fashion. She has a 50% chance of also being a heterozygote from her mother and a 50% chance of being completely unaffected.

Question 80

Reticulate pigmentation of skin, poikiloderma, alopecia, nail atrophy, premalignant oral leukoplakia, and a Fanconi-type pancytopenia resulting in early death in addition to posterior fossa malformations is characteristic of which of the following syndromes. 1 Dyskeratosis congenita 2 Hoyeraal-Hreidarsson syndrome 3 Bloom syndrome 4 Cockayne syndrome 5 Wiskott-Aldrich syndrome

Answer 80

Hoyeraal-Hreidarsson syndrome is has all of the features of dyskeratosis congenita plus posterior fossa malformations. Bloom syndrome and Cockayne syndrome both have poikiloderma as features, but do not include posterior fossa malformations as part of the syndrome. Wiskott-Aldrich syndrome does not include any of these findings.

Question 81

Comma shaped corneal opacities are seen in what disease? 1 Refsum Syndrome 2 Sjogren-Larson Syndrome 3 Pseudoxanthoma elasticum 4 X-linked ichthyosis 5 Proteus syndrome

Answer 81

X-linked ichthyosis is a X-linked recessive disorder secondary to steroid sulfatase deficiency characterized by brown adherent scale. Additional findings include comma-shaped corneal opacities, cryptorchisdism, and failure to progress during labor.

Question 82

Premature aging seen in Cockayne�s syndrome is caused by a mutation in which gene? 1 Transglutaminase 2 ATM gene 3 Patched gene 4 NEMO gene 5 DNA helicase gene

Answer 82

Cockayne's syndrome is caused by a mutation in a DNA helicase gene, CSA or ERCC8. The condition is defined by growth deficiency, premature aging, and pigmentary retinal degeneration. 75% of patient have photosensitive eruptions and severe cataracts before the age of 3 are associated with poor prognosis.

Question 83

What is this syndrome which is histologically characterized by widely dispersed granular material amidst normal fibers? 1 Ehlers Danlos Syndrome 2 Pseudoxanthoma Elasticum 3 Buschke-Ollendorf Syndrome 4 Focal Dermal Hypoplasia 5 Lipoid Proteinosis

Answer 83

Pseudoxanthoma elasticum is genodermatosis characterized by redundant skin, angioid streaks, yellow papules on the mucous membranes and bleeding from gastric artery. On histology, readily apparent denerative changes of the elastic fibers are prominent, even without special stains. Q/Q(M)-476806 Report a Problem

Question 84

A patient with multiple deeply pigmented papules has a skin biopsy which reveals an epitheloid blue nevus. The next appropriate step is: 1 Reassure the patient and follow up as needed 2 Schedule prophylactic excision of the lesion 3 Begin a malignancy work-up 4 Refer to genetics 5 Order an echocardiogram

Answer 84

Epithelioid blue nevi have been reported with and without association with cardiac myxomas as a component of the Carney complex (NAME/LAMB syndrome). Carney complex is an autosomal dominant disorder caused by mutations in PRKAR1A. Patients have cutaneous and atrial myxomas, blue nevi, ephelides, adrenocortical disease, and testicular tumors. Q/Q(M)-477378 Report a Problem

Question 85

What is the most common genetic defect associated with this syndrome? 1 Neurofibromin 2 Merlin 3 Tuberin 4 Hamartin 5 Folliculin

Answer 85

Neurofibromatosis I occur due to a microdeletion at 17q11.2 involving the NF1 gene, which encodes for neurofibromin. It is an autosomal dominant disorder characterized by numerous benign tumors (neurofibromas) of the peripheral nervous system, café au lait macules, freckling in the area of the armpit (crow’s sign), two or more growths on the iris of the eye (known as Lisch nodules or iris hamartomas), tumor on the optic nerve (optic glioma), abnormal development of the spine (scoliosis), the temple (sphenoid) bone of the skull, or the tibia (one of the long bones of the shin) and a first degree relative (parent, sibling, or child) with NF1. The other proteins in the list are associated with other syndromes: In neurofibromatosis type 2, a NF2 gene mutation has been identified which encodes for a protein called Merlin, in tuberous sclerosis two genetic mutations have been identified on two separate chromosomes namely tuberin and hamartin, and a Folliculin mutation is seen in Birt Hogg Dube syndrome. Q/Q(M)-482072 Report a Problem

Question 86

Non-bullous icthyosiform erythroderma is caused by which of the following mutations: 1 Transglutaminase-1 gene (TGM1) 2 12R-lipoxygenase gene (ALOX12B) 3 Lipoxygenase-3 gene (ALOXE3) 4 Both 12R-lipoxygenase gene (ALOX12B) and lipoxygenase-3 gene (ALOXE3) are correct 5 All of these answers are correct

Answer 86

Non-bullous congenital erythroderma (NCIE)is an autosomal recessive disorder characterized by a collodion baby presentation at birth, and generalized erythroderma with fine white scale, palmoplantar keratoderma, and heat intolerance. NCIE may be caused by mutations in transglutaminase-1 gene (TGM1), the 12R-lipoxygenase gene (ALOX12B), and the lipoxygenase-3 gene (ALOXE3). Mutations in the keratinocyte TGM1 gene interferes with normal cross-linking of structural proteins and the lipid envelope, leading to defective cornification and desquamation. ALOXE3 functions as an epoxy alcohol synthase using the product of ALOX12B as the preferred substrate; either gene can be the site of mutations causing NCIE. Q/Q(M)-478118 Report a Problem

Question 87

Which of the following is caused by a defect in lysosomal transport: 1 oculocutaneous albinism I 2 oculocutaneous albinism II 3 Piebaldism 4 Chediak-higashi 5 Bloom�s syndrome

Answer 87

Chediak higashi is an autosomal recessive disorder caused by a mutation in the LYST gene codes for a lysosomal tracking protein. This protein regulates microtubule mediated lysosomal fusion. A defect in this gene leads to giant lysosomal granules seen in neutrophils (leading to defecting phagocytosis and decreased chemotaxis), melanocytes (pigment dilution), and neurons. OCA1 is tyrosinase negative albinism; OCA2 is tyrosinase positive albinism with a mutation in P gene on chromosome 15.

Question 88

The best screening test for hemochromatosis is: 1 Ferritin 2 Hematocrit 3 Complete Blood Count 4 Transferrin 5 Copper levels

Answer 88

The ferritin is the best screening test for hemochromatosis, an autosomal disease of increased intestinal iron absorption. The other tests are not the best method for screening. Q/Q(M)-478061 Report a Problem

Question 89

Which of the following genodermatoses has premalignant oral leukoplakia as a feature? 1 Pachyonychia congenita 2 Dyskeratosis congenita 3 Keratosis follicularis 4 Anhidrotic ectodermal dysplasia 5 Papillon-Lefevre

Answer 89

Dyskeratosis congenita has premalignant oral leukoplakia in addition to cutaneous poikiloderma and nail dystrophy. Pachyonychia congenita also has leukoplakia, but it is benign in nature. Additional features of pachyonychia congenita are thickened nails with nail bed hyperkeratosis and palmoplantar keratoderma. Keratosis follicularis, also known as Darier\'s disease, is characterized by benign whitish papules on the oral mucosa, cutaneous keratotic papules in seborrheic distribution, and longitudinal erythronychia with V-nicking of the distal nail plate. Papillon-Lefevre has gingivitis, without oral leukoplakia, and acral hyperkeratosis. Anhidrotic ectodermal dysplasia does not have leukoplakia. It consists of anhidrosis or hypohidrosis, hypotrichosis, and anodontia. Q/Q(M)-482679 Report a Problem

Question 90

What condition is associated with this finding of inflammatory keratotic facial papules which may result in scarring and atrophy? 1 Chloracne 2 Systemic lupus erythematosus 3 Keratosis pilaris 4 Reiter's syndrome 5 Ulerythema ophryogenes

Answer 90

Ulerythema ophryogenes is a rare disorder that affects children and young adults. It is characterized by keratosis pilaris atrophicans and loss of lateral third of eyebrow. Q/Q(M)-476831 Report a Problem

Question 91

In ataxia telangectasia, the ATM gene is mutated. The product of the ATM gene is an enzyme which: 1 Responds to DNA damage by phosphorylating key DNA repair substrates 2 Binds transforming growth factor beta protein 3 Is the VEGF receptor 3 4 Participates in NF-kB activation 5 Is an inhibitor of G1 cyclin/Cdk complexes

Answer 91

The ATM gene is a member of the phosphatidylinositol-3 family of proteins that respond to DNA damage by phosphorylating key substrates involved in DNA repair according to OMIM. Defects in endoglin (TGF beta3 binding protein) is deficient in Osler-Weber-Rendu syndrome. The VEGF receptor 3 is defective in hereditary lymphedema. The NEMO gene is defective in Incontinentia Pigmenti. Its product, NF-kB essential modulator (NEMO) is a key activator in the NF-kB pathway. KIP2 is involved in AD Beckwith-Wiedemann syndrome and is an inhibitor of G1 cyclin/Cdk complexes. Q/Q(M)-477808 Report a Problem

Question 92

Lamellar ichthyosis is caused by a defect in transglutaminase 1. It can present as a colloidion baby at birth with subsequent large thick plates of scale especially on flexures, ectropion and eclabium. If two unaffected carrier parents have a child, how likely is their child to have this condition? 1 25% 2 75% 3 Only male offspring are affected 4 Only female offspring are affected 5 None of these answers are correct

Answer 92

Lamellar ichthyosis is an autosomal recessive condition. If each parent is a heterozygous carrier, there is a 25% chance that the child will be affected, 50% chance that the child will be a heterozygous carrier and a 25% chance that the child will not be a carrier or affected with lamellar ichthyosis. Q/Q(M)-477719 Report a Problem

Question 93

What is the inheritance pattern of dermatosis with acantholysis? 1 Autosomal dominant 2 Autosomal recessive 3 X-linked dominant 4 X-linked recessive 5 Sporadic

Answer 93

Hailey-Hailey, or Familial Benign Pemphigus, is an autosomal dominant genodermatosis which is caused by a mutation in ATP2C1. Vesicles and erythematous plaques develop in the skin folds such as axillae and groin area. Q/Q(M)-476804 Report a Problem

Question 94

A 3-year old boy has frequent abscesses, chronic ear infections, and severe eczema. He has an older brother with similar problems. What is the gene mutation? 1 Stat 3 gene 2 FBLN 5 gene 3 IL2 receptor gene 4 LEMD3 gene 5 WAS gene

Answer 94

Hyper IgE syndrome (Job syndrome) is associated with severe eczema, recurrent deep-seated abscesses, recurrent pneumonia, and retention of primary teeth. The FBLN5 gene is mutated in cutis laxa. The IL2 receptor gene is mutated in the X-linked recessive form of severe combined immunodeficiency. The LEMD3 gene is mutated in Bushke-Ollendorf syndrome. Wiskott-aldrich syndrome is associated with mutation in the WAS gene and is also associated with eczema and increased bacterial infections. However, it is inherited in a X-linked recessive fashion. Q/Q(M)-482254 Report a Problem

Question 95

A 2 year old patient is small for his age. He has thin, pale, translucent skin, with prominent veins. His father died from aortic rupture when he was in his twenties. Vascular Ehlers-Danlos is caused by mutations in what gene? 1 Type III Collagen 2 Tenascin-X 3 Type V Collagen 4 Lysyl hydroxylase 5 Type I Collagen

Answer 95

Vascular Ehlers-Danlos (Type 4) is characterized by the skin findings discussed above, as well as the onset of severe complications of fragile blood vessels and organs in early adulthood. The disease is inherited in an autosomal dominant manner. Defects are seen in type III collagen. Tenascin-X mutations are seen in hypermobile Ehlers-Danlos (Type 3), type V collagen in classical Ehlers-Danlos (Type 1 and 2), lysyl hydroxylase in kyphoscoliosis Ehlers-Danlos (Type 6), and type I collagen in Ehlers-Danlos types 1, 2, and 7. Q/Q(M)-482613 Report a Problem

Question 96

Which of the following pairs of diseases are caused by mutations in DNA helicases? 1 Bloom syndrome and Rothmund-Thompson syndrome 2 Xeroderma pigmentosum and Cockayne syndrome 3 Muir-Torre syndrome and Birt-Hogg-Dube syndrome 4 Dyskeratosis congenita and Peutz-Jeghers syndrome 5 Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome

Answer 96

Bloom Syndrome and Rothmund-Thompson syndromes are caused by autosomal recessive mutations in DNA helicases. The common features include photodistributed poikiloderma. Patients with Bloom syndrome also demonstrate facial dysmorphism, hypogammaglobulinemia with recurrent respiratory and gastrointestinal tract infections, hypogonadism, leukemias and lymphomas, gastrointestinal adenocarcinomas, and oral/esophageal SCCs. Patients with Rothmund-Thompson syndrome develop premalignant acral keratoses, alopecia, nail dystrophy, cataracts, hypogonadism, and occasional solid tumors. Q/Q(M)-474293 Report a Problem

Question 97

Giant lysosomal granules are seen in which disease? 1 Chediak-Higashi syndrome 2 Griscelli syndrome 3 Piebaldism 4 Incontinentia pigmenti 5 Carney complex

Answer 97

Chediak-Higashi syndrome is caused by an autosomal recessive mutation in a lysosomal transport gene (LYST, CHS1). This disorder is characterized by oculocutaneous albinism, ataxia, muscle weakness, and giant lysosomal granules. There is an accelerated phase characterized by lymphohistiocytic infiltration of reticuloendothelial system, pancytopenia and death. Q/Q(M)-474253 Report a Problem

Question 98

Christ-Siemens-Touraine Syndrome is most commonly linked with defects in which of the following genes? 1 NEMO 2 Ectodysplasin (EDA) 3 ERCC2 4 ATP7A 5 None of these options are correct

Answer 98

Ectodysplasin (EDA) on Xq12-q13 is transmitted in an X-linked recessive fashion and is the most common cause of anhidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome or hypohidrotic ectodermal dysplasia). NEMO can be linked to this syndrome and is associated with immunodeficiency, but this is a rare association. ERCC2 is associated with trichothiodystrophy and ATP7A with Menkes kinky hair syndrome. They are not associated with anhidrotic ectodermal dysplasia. Q/Q(M)-477952 Report a Problem

Question 99

What is the genetic defect of this syndrome? 1 ABCA12 gene 2 Transglutaminase 1 (TGM1). 3 GJB2 (connexin 26) gene. 4 Steroid sulfatase (STS) gene 5 Profilaggrin gene

Answer 99

Mutations in the ABCA12 gene cause harlequin ichthyosis. X-linked ichthyosis (XLI) caused by a steroid sulfatase (STS) deficiency. Keratitis-ichthyosis-deafness syndrome is caused by a mutation in the GJB2 (connexin 26) gene. Ichthyosis vulgaris is caused by a defect in profilaggrin gene and lamellar ichthyosis involves a mutation in the gene for transglutaminase 1 (TGM1). Q/Q(M)-482080 Report a Problem

Question 100

Beckwith-Wiederman syndrome is characterized by which of the following triads? 1 Hemangioblastomas, renal cysts and renal cell carcinoma 2 Epistaxis, telangictases, and gastrointestinal tract bleeding 3 Enlarged limb, port wine stain, and deep venous thrombosis 4 Omphalocele, venous malformations, and ataxia 5 Exomphalos, macroglossia, and gigantism

Answer 100

Beckwith-Wiederman syndrome is also known as EMG syndrome as it includes exomphalos, macroglossia, and gigantism. It is usually a sporadic condition but is sometimes caused by autosomal dominant mutations in p57. Clinical features include facial capillary malformations, macroglossia, visceromegaly with omphalocele, and hemihypertrophy associated with tumors (especially Wilm’s tumors). Q/Q(M)-474263 Report a Problem