Ehlers- Danlos Syndrome Update Overview. All rights reserved. 1. Clair A. Francomano, M.D. Harvey Ins.tute for Human Gene.cs Bal.
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1 Ehlers- Danlos Syndrome Update 2013 Clair A. Francomano, M.D. Harvey Ins.tute for Human Gene.cs Bal.more, Maryland Overview Review of recent literature Data from GBMC A few key points Mul.ple episodes of organ prolapse Kidney Stomach Liver Ovarian All rights reserved. 1
2 20 children with hypermobile EDS and 24 control children Assessed for hypermobility and balance Ac.vi.es of daily living par.cipa.on ques.onnaire Diaries kept of pain and physical ac.vity Excellent review of causes of pain and fa.gue in EDS, hypermobile type All rights reserved. 2
3 Evidence supports decreased posi.on sense in the legs Jury is s.ll out on the upper extremi.es Excellent review of genes causing various forms of EDS as well as the clinical phenotypes. Snapshot vignexes of typical cases All rights reserved. 3
4 Help is On the Way Whole Genome/Exome Sequencing The cost of DNA sequencing has been cut by about 6 orders of magnitude over the past 10 years (from $1 billion to $10-15,000 per genome) NIH has funded three Centers in the US for whole genome sequencing, specifically to find unknown genes causing Mendelian disorders (The Mendel Project). 50 consecu.ve pa.ents with spontaneous CSF leaks were screened for hereditary disorders of connec.ve.ssue. Diagnoses were made in 9 (18%) In 7 pa.ents the CSF leak was the first presen.ng symptom Complex Biomechanical Changes in JHMS/hEDS Most pronounced at pelvis, ankle and distal joints All rights reserved. 4
5 Changes in collagen fibrils found in family members with lower Beighton scores All rights reserved. 5
6 All rights reserved. 6
7 The prevalence of extra musculoskeletal manifesta.ons in pa.ents with Ehlers Danlos syndrome Recent Data from GBMC Objectives To ascertain the prevalence of reported extra musculoskeletal symptoms in a series of pa.ents seen consecu.vely over the last three years To bexer characterize the burden of diseae in pa.ents with Ehlers- Danlos syndrome Prior research Castori, M., Camerota, F., Celle., C., Danese, C., San.lli, V., Saraceni, V.M., Gramma.co, P. Natural history and manifesta.ons of the hypermobility type Ehlers- Danlos syndrome: A pilot study on 21 pa.ents. Am J Med Genet A Mar;152A(3): Maeland, S., Assmus, J., Berglund, B. Subjec.ve health complaints in individuals with Ehlers- Danlos syndrome: A ques.onnaire study. Int J Nurs Stud Jun;48(6): All rights reserved. 7
8 A sequential cohort of 300 patients < 18 years of age 18 (6%) 32 (19%) years 45 (35%) 44 (26%) years 26 (20%) 42 (24%) years 26 (20%) 38 (22) > 50 years 13 (10%) 16 (9%) Number of pa.ents A sequen.al cohort of 300 pa.ents Caucasian 74% 77% Mixed/ Not Caucasian 8% 5% Male** 4% 15% No clinically relevant differences were found between hypermobile and classical pa.ents Mean Beighton scores 7 7 Age < >50 Beighton score All rights reserved. 8
9 Brief Pain Inventory Average pain score 5 5 Worst pain score** 8 7 Age < >50 Average pain score Worst pain score Karnofsky performance status scale 100: I feel normal, no complaints, no evidence of disease 90: I am able to carry on normal ac.vity with minor symptoms 80: I carry on normal ac.vity with effort and some symptoms 70: I am able to care for myself, but unable to carry on normal ac.vi.es 60: I require occasional assistance, but can care for most of my needs 50: I require considerable assistance and frequent care by others 40: I am disabled. I require considerable assistance and frequent care by others 30: I am severely disabled. I am hospitalized, but death is not imminent 20: I am very sick. I require ac.ve suppor.ve care by others 10: I have fatal processes that are rapidly progressing. I am near death Saltzstein B.J., Wyshak G, Hubbusch J.T. Perry J.C. A Naturalis.c study of the chronic fa.gue syndrome among women in primary care. Gen Hosp Psychiatry 1998; 20 (5): All rights reserved. 9
10 Mean Karnofsky scores Age < >50 Karnofsky score : I am able to care for myself, but unable to carry on normal ac.vi.es Cardiovascular symptoms PALPITATIONS SYNCOPE DIZZINESS CHEST PAIN GastrointesPnal symptoms DYSPHAGIA NAUSEA EMESIS** ABD PAIN CONSTIPATION DIARRHEA INCONTINENCE 10 9 All rights reserved. 10
11 Urinary symptoms URGENCY INCONTINENCE FREQUENCY RECURRENT UTI 9 10 HEADACHES Neurologic symptoms MIGRAINES INSOMNIA BRAIN FOG MEMORY LOSS Neurologic symptoms FALLS TREMORS SEIZURES 2 9 NUMBNESS All rights reserved. 11
12 Neurologic symptoms TINNITUS HEARING LOSS FLOATERS HYPEROPIA MYOPIA Psychiatric symptoms MOOD SWINGS** WITHDRAWN ANXIOUS DEPRESSED ADD TEMPERATURE INSTABILITY ConsPtuPonal symptoms WEIGHT GAIN 6 9 WEIGHT LOSS 5 6 All rights reserved. 12
13 Increased Intracranial Pressure Symptoms: Pressure headache, sensi.ve to changes in barometric pressure May present with evidence of CSF leak Some women report increased symptoms around menses Documented by increased pressure on lumbar puncture or intracranial pressure monitoring Mul.ple poten.al causes Chiari, disrup.on of CSF or venous blood flow Responsive to diamox therapy Decreases bicarbonate levels, so monitor closely Mast Cell Disease There is a subset of EDS pa.ents who develop symptoms of mast cell disease (flushing, hives, anaphylaxis) Many of these people respond to therapy for mast cell ac.va.on disorder (H1 and H2 blockers, cromolyn sodium) May reflect increased stress levels and/or autonomic dysfunc.on Drug Metabolism Many EDS pa.ents do not metabolize drugs as expected. Many pa.ents have reported that they are slow to respond to the caine deriva.ves in the dental office need mul.ple injec.ons; wears off very slowly Metabolism of many drugs either prolonged or accelerated What can we learn from these observa.ons about the underlying disorder(s)? All rights reserved. 13
14 Inflamma.on HYDRATION Autonomic Dysfunc.on In EDS Postural Orthosta.c Tachycardia syndrome (POTS) Neurally Mediated Hypotension Gastrointes.nal mo.lity issues Temperature instability Sleep disturbances All rights reserved. 14
15 All rights reserved. 15
16 All rights reserved. 16
17 Relax Thanks to Ms. Christy Haakenson Dr. Anil Mankee Dr. Saqib Baig All our pa.ents and their families All rights reserved. 17
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