11 - 72 - GENETIC DISORDERS AFFECTING DERMAL CONNECTIVE TISSUE Flashcards
most clinically significant EDS subtype because of the risk of arterial or major organ rupture
vascular subtype
Ehlers-Danlos syndromes (EDS) is inherited in what pattern of inheritance?
Autosomal Dominant
Remvig et al criteria for skin hyperextensibility
gene defect in classical EDS
Collagen Type V /(COL5A1, COL5A2)
gene defect in Classical-like EDS
Tenascin XB/(TNXB)
difference of Classical-like EDS from the classic subtype
Hyperextensible skin; easy bruising; hypermobile joints; without atrophic scarring (present in classic EDS); muscle weakness; acrogeria; axonal polyneuropathy
inheritance of classical-like EDS
AR
major protein/gene defect of vascular EDS
collagen Type III/(COL3A1)
Major criteria of classical EDS
- Skin hyperextensibility (Remvig) and atrophic scarring
- Generalized joint hypermobility (GJH) (Beighton)
Minor criteria of classical EDS
criteria required for diagnosis of classical EDS
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?
Gorlin sign
Beighton Criteria for Joint Hypermobility
classic quadrad of vEDS
- facial appearance (which may be subtle) - thin nose and upper lip, small earlobes, and sunken, pigmented periocular regions
- thin, translucent skin with a prominent venous pattern
- extensive bruising or hematomas,
- vascular or visceral rupture (or both)
most common cause of death in vascular EDS
arterial rupture
this test is used to distinguish hEDS (hypermobility type) skin from normal
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
pattern inheritance of Marfan syndrome
Autosomal dominant
protein/gene mutated in marfan syndrome
fibrillin 1 (FBN1)
Marfan syndrome is a generalized connective tissue disorder exhibiting abnormalities of what 3 primary organ systems?
- ocular
- skeletal
- cardiovascular
thumb extends well beyond the ulnar border of the hand when overlapped by the fingers
Steinberg sign
thumb overlaps the fifth finger as they grasp the opposite wrist
Walker-Murdoch sign
most common cardiovascular defect in marfan syndrome
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.
pattern of inheritance of pseudoxanthoma elasticum
Autosomal recessive
most common cutaneous manifestations of Marfan syndrome
Lack of subcutaneous fat and the presence of striae, most prominent on the upper chest, arms, thighs, and abdomen,
gene mutation of pseudoxanthoma elasticum
ABCC6 gene
- 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
pseudoxanthoma elasticum
Histopathologic findings of pseudoxanthoma elasticum
- 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
Also known as Grönblad-Strandberg syndrome, this rare entity is a heritable ectopic mineralization disorder exhibiting progressive deposition of calcium hydroxyapatite on elastic tissue.
pseudoxanthoma elasticum
skin lesions are likened to a “plucked chicken skin” appearance
pseudoxanthoma elasticum
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.
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?
pseudoxanthoma elasticum
most common ophthalmologic finding in PXE
angioid streaks (87% of patients)
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.
These changes precede angioid streaks and are the more common ocular finding in children with PXE.
Peau d’orange retinal changes
most common late vascular sequelae in PXE
intermittent claudication
this drug may induce an acquired form of PXE
D-Penicillamine
- 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
cutis laxa
- 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.
Progressive exostoses including “occipital horns” is a manifestation of what subtype of cutis laxa?
XLR CL
protein/gene defect in AD CL
Elastin (ELN/130160)
Fibulin 5 (FBLN5/604580)
protein/gene defect in XLR CL
α Polypeptide of Cu 2+ transporting adenosine triphosphatase (ATPase)
histopath findings of cutis laxa
- Special stains for elastic tissue (Verhoeff-van Gieson stain) of skin biopsy specimens demonstrate significantly 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
most frequent cause of death in acquired cases of cutis laxa
Pulmonary involvement presents as emphysema
- 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 eruption (urticaria, erythema multiforme, eczematous eruption) in approximately 50% of cases.
Type I-acquired CL
- 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.
Type II-acquired CL (Marshall syndrome)
Acquired CL may develop after exposure to what drugs?
penicillin, D-penicillamine, or isoniazid
pattern of inheritance of BUSCHKEOLLENDORFF SYNDROME
Autosomal dominant
gene mutated in BUSCHKEOLLENDORFF SYNDROME
LEMD3 gene
Cutaneous features include elastomas and collagenomas (dermatofibrosis lenticularis disseminata)
BUSCHKE-OLLENDORFF SYNDROME
cutaneous and noncutaneous features of Buschke-Ollendorff Syndrome
- elastoma
- collagenoma
- osteopoikilosis (seen in radiograph)
pattern of inheritance of lipoid proteinosis
AR
protein/gene defect in lipoid proteinosis
extracellular matrix protein-1 (ECM-1)
most frequent finding of lipoid proteinosis
Hoarseness
**Beaded papules on the eyelid margin (moniliform blepharosis) **are a classic finding in adolescents and adults, but are not always present.
Lipoid proteinosis
most reliable clinical signs for diagnosing lipoid proteinosis
hoarse voice and thickened sublingual frenulum, which prevents patients from protruding the tongue
- 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
earliest finding in lipoid proteinosis
hoarseness from vocal cord infiltration, which occurs at birth or in the first few years of life
- 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.
pathognomonic clinical finding of lipoid proteinosis
beaded papules along the eyelid margins (moniliform blepharosis)
