Classical Ehlers-Danlos Syndrome

Transcription

1 Classical Ehlers-Danlos Syndrome Clair A. Francomano, MD EDS Center for Clinical Care and Research Harvey Ins>tute for Human Gene>cs Greater Bal>more Medical Center

2 Commi5ee Members Jessica M. Bowen Glenda J. Sobey Nigel P. Burrows Marina Columbi Mark Lavallee Fransiska Malfait Chris>na Schwar>ng Clair A. Francomano

3 Classical EDS: History Beighton, 1968: EDS Gravis and Mi>s Beighton, 1988: EDS Types I and II Villefranche nosology, 1997: Classical EDS 1996: Iden>fica>on of muta>ons in COL5A1 (Nicholls et al., 1996; Wenstrup et al., 1996; De Paepe et al., 1997)

4 Recommended Naming Retain the name Classical Ehlers-Danlos Syndrome Abbrevia>on: ceds

5 Proposed Criteria Major criteria 1. Skin hyperextensibility and atrophic scarring 2. Joint hypermobility

6 Minor Criteria 1. Easy bruising 2. So`, doughy skin 3. Skin fragility (or trauma>c splibng) 4. Molluscoid pseudotumours 5. Subcutaneous spheroids 6. Hernia (or history thereof) 7. Epicanthal folds 8. Family history of a first degree rela>ve who meets clinical criteria

7 To Establish a Clinical Diagnosis Major Criterion (1): Skin hyperextensibility and atrophic scarring Plus Either: Major criteria (2) joint hypermobility Or: three of the eight minor criteria

8 Clinical Skin is considered hyperextensible if it can be stretched over a standardized cut off in three of the following areas 1.5 cm for the distal part of the forearms and the dorsum of the hands 3 cm for neck, elbow and knees

9 Skin Hyperextensibility

10 Scarring Abnormal scarring can range in severity. Most pa>ents have extensive atrophic scars at a number of sites. These can some>mes be haemosidero>c. A minority of pa>ents are more mildly affected.

11 Scarring

12 Joint Hypermobility Joint hypermobility is assessed through the Beighton score. A score of 5 or more is considered posi>ve for the presence of joint laxity

13 Beighton Scale

14 Clinical (2) Easy bruising can occur anywhere on the body, including unusual sites. The pre>bial area o`en remains stained with hemosiderin from previous bruises

15 Bruising

16 Subjec>ve abnormality of the skin texture is appreciable on exam Molluscoid pseudotumors are fleshy lesions associated with scars, found over pressure points (e.g. elbow, fingers)

17 Molluscoid Pseudotumors

18 Clinical (3) Subcutaneous spheroids are small spherical hard bodies, frequently mobile and palpable on the forearms and shins. Spheroids may be calcified and detectable radiologically Epicanthal folds are o`en seen in childhood but may also be seen in adults.

19 of Clinical Diagnosis Confirmatory analysis is recommended for any pa>ent mee>ng the recommended clinical criteria. Molecular analysis of COL5A1 and COL5A2 genes iden>fies a causal muta>on in more than 90% of the pa>ents and should be used as the standard confirmatory test. In case of unavailability of gene>c tes>ng, electron microscopy findings of collagen flowers on skin biopsy can support the clinical diagnosis. Absence of these confirmatory findings does not exclude the diagnosis, however alterna>ve diagnoses should be considered in the absence of a type V collagen gene muta>on or electron microscopy findings.

20 HUMAN MUTATION, Vol. 33, No. 10, , 2012

21 Organ System Review Musculoskeletal Skin Cardiovascular Gastrointes>nal Neurologic

22 Musculoskeletal Joint hypermobility Complica>ons of joint hypermobility Mild muscle hypotonia Skeletal morphology altera>ons Increased bone fragility (osteopenia or osteoporosis)

23 Skin Stretchy So` Severe atrophic scarring Hemosideric scars over the shins and extensor surfaces of the forearm Easy bruising

24 Cardiovascular Aor>c root dila>on; rarely progresses Mitral valve prolapse Venous insufficiency

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26 Dysphagia Dyspepsia Gastro-esophageal reflux Hiatal hernia Irritable bowel syndrome Unspecified abdominal pain Cons>pa>on Diarrhea Rectocoele

27 Neurologic Pain Dysautonomia Headache Frequency of Chiari I, craniocervical instability, tethered cord as yet undefined.

28 Others Prolonged bleeding >me Chronic fa>gue syndrome Mast cell ac>va>on Giant bladder diver>culi

29 Management - Skin Avoidance of trauma Closure of wounds plas>c surgeon if possible Ascorbic acid (2 gm/day for adults) DDAVP may help to normalize bleeding >me Avoid excessive sun exposure

30 Management - Muscloskeletal Physiotherapy Avoid high-impact ac>vi>es Avoid excessive demonstra>ons of hypermobility A mul>-disciplinary team is very helpful for management Ring splints, carefully considered bracing and ortho>cs may be helpful DEXA analysis

31 Management Pain Neurological assessment in pa>ents with symptoms sugges>ve of neuropathic pain/compression neuropathy Regular, light, non-weight-bearing exercise. Physical therapy for muscle relaxa>on and myofascial trigger point release Relaxa>on techniques including mindfulness-based stress reduc>on and biofeedback Counselling support including cogni>ve behavioural therapy An>-inflammatory drugs and pain medica>ons

32 Management - Cardiac Echocardiography to look for aor>c root dila>on and mitral valve prolapse. Aor>c root size and mitral valve prolapse are increased in pa>ents with classical EDS, but they tend to be of liole clinical significance. Echo frequency in symptom-free adults frequency can be reduced (Atzinger et al., 2011). If echo is normal in adulthood no follow up is required (Malfait et al., 2010). Consider vascular imaging /agreessive blood pressure control if the pa>ent has a glycine subs>tu>on iden>fied near the C-terminal end of the triple helix, or on the basis of their family history (Monroe et al., 2015)

33 Management - Gastrointes@nal Upper gastrointes>nal endoscopy or 24 h ph-metry to evaluate reflux disease in symptoma>c pa>ents. Treatment with proton-pump inhibitor if needed Colonoscopy should be performed with care due to a possibly increased risk of mucosal bleeding Treatment of func>onal gastrointes>nal complaints in EDS pa>ents is problema>c due to the absence of tailored strategies and an apparent resistance to pharmacologic treatments at standard dosages/regimens. Pa>ent educa>on, also comprising diet and nutri>onal advice, seems at the moment the most effec>ve management tool

34 Management - Pregnancy Follow up throughout pregnancy is warranted. Prematurity happens more o`en when the fetus is affected and is mainly due to premature rupture of the membranes Breech presenta>on is more common if the baby is affected, due to hypotonia

35 Diagnosis Cardiac-valvular type EDS Tenascin X deficient EDS Spondylocheirodysplas>c type EDS Loeys Dietz syndrome OI/EDS overlap syndrome

36 Thanks The Classical EDS commioee Our pa>ents and their families The Ehlers-Danlos Society and EDS-UK Lara Bloom and Shane Robinson