Inherited CTD Flashcards
General Features of Ehlers Danlos Syndrome
Classic EDS genes AD mutations COL5A1 &2 impaired collagen synthesis
Cutaneous
• Hyperextensible skin – measure volar surface of distal wrist/forearm, upper limit normal 1-1.5cm
• Soft doughy texture Classic and Dermatosparaxis
• Fragile skin – splits easily particularly over sites of trauma
• Easy bruising (from fragile blod vessels), visible veins (vascular)
• Poor wound healing (cigarette paper scars)– delayed
• Scarring - Heal with atrophic “fish mouth scars”. Occasionally hypertrophy rather than atrophic scars
• Gorlin Sign – touch tip of tongue to nose – Classic EDS (vs 10% of general population)
• “Secondary lesions” - MS
• Molloscoid tumours – fleshy nodules of redundant skin and fibrous tissue associated with scars
• Subcutaneous spheroids – small hard mobile nodules over bony prominences (ulnar and tibial); calcified fat globules
• Associated derm disorders
• Elastosis perforans serpiginosa
• Piezogenic papules – herniations of fat through tissue
Summary of extracutaneous features
• “Facies” with vascular subtype – reduced adipose tissue
• Joint - Joint hypermobility(measured using Beighton Scale),double jointed fingers, frequent subluxation of larger joints), Pes Planus, kyphoscoliosis
• Muscle - Hypotonia.
• Vascular – arterial, intestinal, uterine rupture
• GIT – bleed/rupture (vascular subtype), hernias
• Cardiac – mitral valve prolapse, aortic root dilation
• O&G – PROM, umbilical hernias – Dermatosparaxis
• Autonomic dysfunction = orthostatic hypotension, GIT symptoms – occurs in hypermobile subtype (commonest)
• Neuro – developmental delay (kyphoscoliotic)
• Ocular – rupture of ocular globe (kyphoscoliotic), blue sclera (Dermatosparaxis)
• Dental– gingival hyperplasia – Dermatopraxis, periodontal subtypes
Vascular EDS presentation
AD COL3A1 mutation
- Life-threatening risk of blood vessel and organ rupture → sudden death in third/fourth decade (arterial or colonic rupture; maternal death may occur as a result of uterine or arterial rupture)
- Cutaneous manifestations
• Easy bruising
• Thin and translucent skin with visible underlying blood vessels
• Skin is not hyperextensible, but can be fragile
• Lack of subcutaneous fat - Facial features: thin, pinched nose; prominent sunken eyes; thin upper lip; and lobeless ears, Blue sclera (>90%)
- Acrogeria
- Hypermobility limited to digits, Congenital talipes (club foot)
- Recurrent pneumothoraces
- Arterial (including aorta) dissection, rupture, and aneurysm of medium-sized vessels
- Spontaneous rupture of arteries (medium-sized) may occur during childhood, and incidence peaks during third and fourth decade
- Intestinal rupture is common (sigmoid colon #1 site)
- Intracranial aneurysms associated with cerebrovascular accidents
- Obstetric complications, including uterine and arterial rupture, massive postpartum hemorrhage, and severe laceration from tearing at vaginal delivery
- Short stature
Hypermobile EDS
Commonest form
AR mutation tenascin X
Hypermobile EDS
Not prone to life-threatening complications
Severe joint laxity, recurrent dislocations/subluxations, and chronic joint pain +/− arthritis
Mitral valve prolapse
Symptoms of autonomic dysfunction, including postural orthostatic tachycardia syndrome (POTS)
GI and urinary symptoms
EDS general management
Examination – skin, scleria, facies, gorlins sign, joints (Beighton scale), CVS exam with referral.
Beighton scale of 9 – passive dorsiflexion of thumb to forearm, little finger greater 90 degrees, hyperextension knees/elbows >10 degrees, flexion towards floor touching palms flat.
Management
Educate – inheritance, explaination of condition, common and uncommon complications, no cure, management
Genetic counselling to delineate subtype
Letter to GP + MDT (orthopaedics, vascular surgeons)
General measures – avoid trauma sports, plan carefully for surgery, sutures may need to remain in longer
Vascular subtype often managed with B blockers
High risk pregnancy
FOLLOW UP
PXE
Pathogenesis and histo
AR; Loss of function in both copies of ABCC6
This encodes and ATP pump on hepatocytes.
Reduced ATP secretion reduced plasma concentrations of PPI (inorganic pyrophosphatase) which is a mineralization inhibitor
Reduce anti-mineralization activity increased calcification of mid/deep dermis, medium sized arteries and Bruchs membrane of the eye
Histo - distorted, basophilic, and fragmented calcified elastic fibersin mid/deep reticular dermis
Stains – Von Kossa= Calcium; Verhoeff-van Gieson=Elastin
PXE Management
Examination – skin, opthal review, CVS review
Educate patient – inheritance, risk transmission, common/uncommon complications, no cure, general management
Genetics referral
Referral to opthal – fundoscopy/visual field, general (avoid trauma, avoid smoking, wear sunglasses); VGEF intravitreal injections, laser
cardiac reg reviews – CVS examination, echo, lifestyle optimization, +/- management of other risk factors (hypercholesterolaemia, HTN, DM)
Planned pregnancy
Annual FU with derm. Surgical removal excess skin folds, ?CO2 laser reported for cobblestonning.
PXE Clinical presentation
Clinical
Childhood onset of skin manifestations but dx often delayed until 30-40s when systemic/ocular complications arise
Affects – Skin, Eyes, CVS
Skin
10-20 yo yellow papules coalesce to form “cobblestone” plaques “plucked chicken skin”
Lateral neck first, then other flexural sites (antecubital fossa, popliteal fossa, wrists, axilla, groin). Can affect umbilicus in multiparous women. Rarely generalized.
Mucosal – yellow papules, commonly lower lip
Prominent creases on the chin – in 2/3 of pts <30yo and majority of older pts.
Perforating PXE – overtime papules may calcify become firm and extrude yellow material.
Sagging skin – mostly in axilla, groin. Due to loss of elastic fibres and recoil. (considered secondary cutis laxa)
Ocular
Angoid streaks (image A)– present in first decade. Occur in all pts by 30yo. Breaks in calcified elastic Bruchs membrane (formed by retina and choroid plexus). Asymptomatic. However breaks lead to neovascularization haemorrage scar central progressive visual loss by 40yo +/- blindness (uncommon)
Mottling of retinal pigment (image B)– COMMONEST ocular change. Known as “peau d’orange changes” May preceed angoid streaks.
Less common – macular degeneration, optic drusen, “owls eyes” (paired hyperpigmented spots)
Cardiovascular
Progressive calcification of medium sized arteries (intima and media) especially of limbs formation of atherosclerotic plaques. CVS complications (all occur at much younger age than gen pop) are all sequlae of this and can include:
Intermittent claudication, loss peripheral pulses
Renovascular HTN
Angina, MI, stroke
Increased risk MVP (mitral valve prolapse)
GI manifestations
Gastric artery hemorrhage, hematemesis, epistaxis
Obstetric complications
↑risk offirst trimester miscarriageand maternal cardiovascular complications
Cutis laxa
XR (commonest and most severe), XLR and AD.
AR Presents at birth/early childhood (fibrillin 5); AD early adulthood (elastin or fibrillin 5)
Histo – sparse/absent elastic fibres
Skin manifestations
“Aged” facial appearance (hound-dog facies)with down-slanting palpebral fissures and a long philtrum
Loose, sagging skinwith reduced elasticity and resilience; deep voice 2° to vocal cord laxity
Extracutaneous
Less common in AD
Severe in AR lungs (hypoplastic + emphysema), cardiac (aneurysms), hernias and diverticula +/- developmental delay, craniofacial abnormalities
AR Type II can improve with age.
