Inherited Connective Tissue Disorders Flashcards
What is the most common form of cutis laxa/generalized elastolysis?
Autosomal Recessive
What genes are involved in the AD form of cutis laxa/generalized elastolysis?
Elastin (ELN) and fibulin 5 (FBLN5)
What do the mutations in ELN or FBLN5 in cutis laxa/generalized elastolysis lead to?
Dysregulation of elastic fiber network in skin mainly (uncommon to get internal involvement)
What age do patients with AD cutis laxa/generalized elastolysis present?
Early adulthood
What is one major difference between AD and AR cutis laxa/generalized elastolysis?
The AR form has severe internal organ involvement
What genes are involved in the AR forms of cutis laxa/generalized elastolysis?
FBLN5, EFEMP2/FBLN4, LTBP4, ATPase, ATP6V0A2 and others
What is the XLR form of cutis laxa?
Was called occipital horn syndrome (previously know as EDS IX)
- Caused from mutations in ATPase, Cu2+ transporters, alpha polypeptide (ATP7A) (allelic to menkes dz)
Clinical appearance of cutis laxa?
Loose, sagging skin w/ reduced elasticity and resilience
- Pts also get deep voice from vocal cord laxity
Histology of cutis laxa?
Sparse and or fragmented elastic fibers
Clinical findings of AD cutis laxa?
Loose, sagging skin w/ reduced elasticity and resilience, cardiac valve abnormalities, aortic dilation (variable), emphysema (uncommon), and hernias
Clinical findings in AR cutis laxa type I?
Potentially fatal involvement of the lungs (hypoplastic and emphysema)
- cardiovascular abnormalities (aortic tortuosity and aneurysms)
- Inguinal/diaphragmatic/umbilical hernias
- GI diverticula or genitourinary diverticula
- Joint laxity, arachnodactyly, and fractures
Clinical findings in AR cutis laxa type II?
Craniofacial abnormalities, delayed growth and development, cutaneous findings can be mostly acral, pachygyria (IIA) and absent corpus callosum (IIB), translucent skin (IIB), joint laxity, strabismus/myopia, improves with age
Clinical findings in AR cutis laxa type III?
- Developmental delay/dystonia/neurologic deterioration
- Progeroid appearance
- Reduced subcutaneous fat
- Reduced subcutaneous fat
- Athetosis
- Hyperammonemia
- Corneal clouding/cataracts
Clinical findings in XLR cutis laxa (Occipital horn syndrome)?
- Easy bruising and coarse hair
- Tortuous arteries
- Genitourinary diverticula
- Inguinal, diaphragmatic and umbilical hernias
- Long face w/ high forehead and hooked nose
- Wedge-shaped occipital calcifications
- Hip dislocations
What is acquired cutis laxa?
Primarily in adults w/ sagging skin and little associated internal involvement
- Cutaneous involvement tends to be primarily acral; generalized involvement usually occurs on face/neck
- Can be associated with drugs (penicillamine and isoniazid), other disorders (cutaneous lymphoma, Sweet syndrome-like eruption, interstitial granulomatous dermatitis, and cutaneous mastocytosis and systemic dz (RF, sarcoidosis, SLE, and infectious disorders
What are the genetics of pseudoxanthoma elasticum?
AR
-Mutations in ABCC6 (ATP-binding cassette, subfamily C, member 6) gene –> secondary mineralization of the elastic tissue of the eyes, skin and arteries
When does pseudoxanthoma elasticum tend to present?
Childhood or the 2nd/3rd decade of life
Cutaneous manifestations of pseudoxanthoma elasticum?
- Thin, yellowish papules in flexural areas arising in the first or second decades of life
- typically first appear on the lateral aspects of the neck
- Papules coalesce to form cobblestone-like plaques resembling “plucked chicken skin”
- Antecubital and popliteal fossae, wrists, axillae, groin, and periumbilical area (in multiparous women) are involved
- Loss of recoid and sagging skin in axillae and grown
- Can get yellow papules in the oral/anogenital mucosa
What is perforating pseudoxanthoma elasticum?
Happens in advanced dz: increased dermal calcium deposition and extrusion of yellowish material through the epidermis
What are the ocular manifestations of pseudoxanthoma elasticum?
- Asymptomatic angioid streaks, usually occur in the first decade. This usually looks like “owl’s eyes” paired areas of hyperpigmented spots straddling an angioid streak
- macular degeneration, optic drusen, retinal hemorrhage, mottling of the retinal pigment epithelium (most prevalent ophthalmologic finding, can precede the formation of angioid streaks
What other conditions can have angiod streaks?
Paget’s disease of bone, sickle cell anemia, thalassemia, EDS, lead poisoning, and age-related degeneration
What are the cardiovascular manifestations of pseudoxanthoma elasticum?
Intermittent claudication, loss of peripheral pulses, renovascular hypertension, mitral valve prolapse, angina/myocardial infarction, and stroke
-Progressive clacification of elastic media and intima –> atheromatous plaques involving predominantly medium-sized arteries (esp in extremities)
What are the GI manifestations of pseudoxanthoma elasticum?
Gastric artery hemorrhage (aneurysms), hematemesis, epistaxis
What are the obstetric pseudoxanthoma elasticum?
Increased risk of first trimester miscarriage and maternal cardiovascular complications