11 - 72 - GENETIC DISORDERS AFFECTING DERMAL CONNECTIVE TISSUE

Question 1

most clinically significant EDS subtype because of the risk of arterial or major organ rupture

Answer 1

vascular subtype

Question 2

Ehlers-Danlos syndromes (EDS) is inherited in what pattern of inheritance?

Answer 2

Autosomal Dominant

Question 3

Remvig et al criteria for skin hyperextensibility

Answer 3

Question 4

gene defect in classical EDS

Answer 4

Collagen Type V /(COL5A1, COL5A2)

Question 5

gene defect in Classical-like EDS

Answer 5

Tenascin XB/(TNXB)

Question 6

difference of Classical-like EDS from the classic subtype

Answer 6

Hyperextensible skin; easy bruising; hypermobile joints; without atrophic scarring (present in classic EDS); muscle weakness; acrogeria; axonal polyneuropathy

Question 7

inheritance of classical-like EDS

Answer 7

AR

Question 8

major protein/gene defect of vascular EDS

Answer 8

collagen Type III/(COL3A1)

Question 9

Major criteria of classical EDS

Answer 9

1. Skin hyperextensibility (Remvig) and atrophic scarring
2. Generalized joint hypermobility (GJH) (Beighton)

Question 10

Minor criteria of classical EDS

Answer 10

Question 11

criteria required for diagnosis of classical EDS

Answer 11

Question 12

Most patients with cEDS or hypermobile EDS (hEDS) are able to extend the tongue to touch the tip of the nose. What do you call this sign?

Answer 12

Gorlin sign

Question 13

Beighton Criteria for Joint Hypermobility

Answer 13

Question 14

classic quadrad of vEDS

Answer 14

1. facial appearance (which may be subtle) - thin nose and upper lip, small earlobes, and sunken, pigmented periocular regions
2. thin, translucent skin with a prominent venous pattern
3. extensive bruising or hematomas,
4. vascular or visceral rupture (or both)

Question 15

most common cause of death in vascular EDS

Answer 15

arterial rupture

Question 16

this test is used to distinguish hEDS (hypermobility type) skin from normal

Answer 16

rubber glove skin test

In this clinical test, the skin of the patient’s dorsal hand is pulled upwards and is noted to stretch over a much wider area than typical, often extending to the wrist and beyond. The stretching of the skin mimics that seen when pulling on the back of a rubber glove while wearing it on the hand

Question 17

pattern inheritance of Marfan syndrome

Answer 17

Autosomal dominant

Question 18

protein/gene mutated in marfan syndrome

Answer 18

fibrillin 1 (FBN1)

Question 19

Marfan syndrome is a generalized connective tissue disorder exhibiting abnormalities of what 3 primary organ systems?

Answer 19

• ocular
• skeletal
• cardiovascular

Question 20

thumb extends well beyond the ulnar border of the hand when overlapped by the fingers

Answer 20

Steinberg sign

Question 21

thumb overlaps the fifth finger as they grasp the opposite wrist

Answer 21

Walker-Murdoch sign

Question 22

most common cardiovascular defect in marfan syndrome

Answer 22

Medial necrosis of the aorta

Death in Marfan patients usually occurs in adulthood as a result of CV sequelae, most commonly secondary to dilation of the aortic root, leading to aortic dissection or rupture and pericardial tamponade.

Question 23

pattern of inheritance of pseudoxanthoma elasticum

Answer 23

Autosomal recessive

Question 23

most common cutaneous manifestations of Marfan syndrome

Answer 23

Lack of subcutaneous fat and the presence of striae, most prominent on the upper chest, arms, thighs, and abdomen,

Question 23

gene mutation of pseudoxanthoma elasticum

Answer 23

ABCC6 gene

Question 24

* Cutaneous features include **yellow, flat papules in the neck, flexures, and periumbilical areas.** * Less-frequent skin lesions include **acneiform** lesions, **elastosis perforans serpiginosa, **reticulate pigmentation, and granulomatous nodules. * Extracutaneous manifestations include angioid streaks, visual impairment, peau d’orange retinal hyperpigmentation, cardiovascular disease, and bleeding. * Breast and testicular microcalcifications occur and may be mistaken for malignancy

Answer 24

pseudoxanthoma elasticum

Question 24

Histopathologic findings of pseudoxanthoma elasticum

Answer 24

* swollen, clumped, fragmented elastic fibers and calcium deposits in the mid and deep reticular dermis. * Alterations are easily visualized with calcium (ie, **von Kossa**) and elastic (ie, **Verhoeff-van Gieson or orcein**) stains * distinctive broken curls of basophilic elastic fibers with routine hematoxylin and eosin or Verhoeff-van Gieson staining

Question 25

Also known as Grönblad-Strandberg syndrome, this rare entity is a heritable ectopic mineralization disorder exhibiting progressive deposition of calcium hydroxyapatite on elastic tissue.

Answer 25

pseudoxanthoma elasticum

Question 26

skin lesions are likened to a "plucked chicken skin" appearance

Answer 26

pseudoxanthoma elasticum ## Footnote Typically, the skin in PXE demonstrates yellowish, flat-topped, discrete, and confluent papules in the skin creases of the sides and nape of the neck, perineum, axillae, umbilicus, and flexural folds with skin redundancy that increases with advancing age.

Question 27

Some authors suggest that **prominence of the horizontal and oblique mental creases** (which separate the lower lip from the chin)** prior to 30 years** of age is highly specific for what condition?

Answer 27

pseudoxanthoma elasticum

Question 28

most common ophthalmologic finding in PXE

Answer 28

angioid streaks (87% of patients) ## Footnote These are radial curvilinear extensions of gray, brown, or reddish coloration from the optic disc, caused by visualization of the choroid through tears in the elastic-rich Bruch membrane.

Question 29

These changes precede angioid streaks and are the more common ocular finding in children with PXE.

Answer 29

Peau d’orange retinal changes

Question 30

most common late vascular sequelae in PXE

Answer 30

intermittent claudication

Question 31

this drug may induce an acquired form of PXE

Answer 31

D-Penicillamine

Question 32

* Skin is inelastic and appears pendulous. * At birth infants appear to have unusually soft and loose skin. * The skin is hyperextensible, but **does not resume or slowly resumes its normal shape after stretching**

Answer 32

cutis laxa ## Footnote * Persons with CL are often described as having a bloodhound-like facial appearance * Young, affected children appear aged. * Signs of skin fragility, easy bruising, or abnormal scarring are typically absent in contrast to EDS.

Question 33

Progressive exostoses including “occipital horns” is a manifestation of what subtype of cutis laxa?

Answer 33

XLR CL

Question 34

protein/gene defect in AD CL

Answer 34

Elastin (ELN/130160) Fibulin 5 (FBLN5/604580)

Question 35

protein/gene defect in XLR CL

Answer 35

α Polypeptide of Cu 2+ transporting adenosine triphosphatase (ATPase)

Question 36

histopath findings of cutis laxa

Answer 36

* Special stains for elastic tissue (Verhoeff-van Gieson stain) of skin biopsy specimens demonstrate s**ignificantly decreased or absent dermal elastic fibers** (in both AD and AR forms of CL). * Remaining fibers are often clumped, short, granular, and fragmented. Increased elastin-associated microfibrils are noted on electron microscopy

Question 37

most frequent cause of death in acquired cases of cutis laxa

Answer 37

Pulmonary involvement presents as emphysema

Question 38

* type of acquired cutis laxa characterized as** ll-defined areas of loose skin appear insidiously but progressively with elastolysis** occurring beyond inflammatory areas in many cases * skin lesions involve the **head and neck** and progress in a cephalocaudal direction. * The development of CL is **preceded by an inflammatory eruptio**n (urticaria, erythema multiforme, eczematous eruption) in approximately 50% of cases.

Answer 38

Type I-acquired CL

Question 39

* type of cutis laxa characterized by postinflammatory elastolysis characterized by more localized, well-demarcated, nonpruritic erythematous plaques that extend peripherally and have a hypopigmented center.

Answer 39

Type II-acquired CL (Marshall syndrome)

Question 40

Acquired CL may develop after exposure to what drugs?

Answer 40

penicillin, D-penicillamine, or isoniazid

Question 41

pattern of inheritance of BUSCHKEOLLENDORFF SYNDROME

Answer 41

Autosomal dominant

Question 42

gene mutated in BUSCHKEOLLENDORFF SYNDROME

Answer 42

LEMD3 gene

Question 43

Cutaneous features include **elastomas** and **collagenomas** (dermatofibrosis lenticularis disseminata)

Answer 43

BUSCHKE-OLLENDORFF SYNDROME

Question 44

cutaneous and noncutaneous features of Buschke-Ollendorff Syndrome

Answer 44

* elastoma * collagenoma * osteopoikilosis (seen in radiograph)

Question 45

pattern of inheritance of lipoid proteinosis

Answer 45

AR

Question 46

protein/gene defect in lipoid proteinosis

Answer 46

extracellular matrix protein-1 (ECM-1)

Question 47

most frequent finding of lipoid proteinosis

Answer 47

Hoarseness

Question 48

**Beaded papules on the eyelid margin (moniliform blepharosis) **are a classic finding in adolescents and adults, but are not always present.

Answer 48

Lipoid proteinosis

Question 49

most reliable clinical signs for diagnosing lipoid proteinosis

Answer 49

**hoarse voice and thickened sublingual frenulum**, which prevents patients from protruding the tongue ## Footnote * Secondary features include beaded eyelid papules, infiltration of warty papules of the skin around the elbows and extensor forearms, and mild alopecia. * Increased scarring and photoaging of sun-exposed skin may be seen. * Scars or scar-like lesions are present in areas of minor trauma but are not increased at sites of surgery or vaccination

Question 50

earliest finding in lipoid proteinosis

Answer 50

**hoarseness** from vocal cord infiltration, which occurs at birth or in the first few years of life ## Footnote * Initially, this may be noted as a faint or weak cry and is one of the most striking and consistent features * Hoarseness may progress during the lifetime of a patient.

Question 51

pathognomonic clinical finding of lipoid proteinosis

Answer 51

beaded papules along the eyelid margins (moniliform blepharosis)