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Dr Prasanth Sankar Prof. E. Dhandapani’s Unit Stanley Medical College
<ul><li>Faiyaz </li></ul><ul><li>22y male D.O.A:7-3-10 ;9.30 pm </li></ul><ul><li>Chennai </li></ul><ul><ul><li>Admitted t...
<ul><li>O/E </li></ul><ul><li>Patient conscious, oriented, cooperative </li></ul><ul><li>No pallor, icterus, cyanosis, clu...
<ul><li>Anthropometry </li></ul><ul><li>Height – 180 cm </li></ul><ul><li>Weight – 60 kg </li></ul><ul><li>BMI – 18.50 </l...
 
 
 
 
<ul><li>CBC, RFT, RUE, LFT – WNL </li></ul><ul><li>Ecg – NSR, WNL </li></ul><ul><li>X –Ray Chest </li></ul><ul><li>X–Ray P...
<ul><li>Echo </li></ul><ul><ul><li>Bicuspid aortic valve </li></ul></ul><ul><ul><li>No AS/AR </li></ul></ul><ul><ul><li>Ao...
<ul><li>Ophthalmology evaluation </li></ul><ul><ul><li>Lids, cornea, conjunctiva – normal </li></ul></ul><ul><ul><li>Ant c...
<ul><li>DIAGNOSIS </li></ul><ul><ul><li>ALCOHOL INTOXICATION/ HYPOGLYCEMIA/ </li></ul></ul><ul><ul><li>MARFAN SYNDROME </l...
<ul><li>AD- mutations in  fbn1  gene on chromosome 15 </li></ul><ul><li>Abnormalities in  TGF β -signaling – new culprit <...
<ul><li>Index case: </li></ul><ul><ul><li>If the family/genetic history is not contributory,  major criteria  in ≥2 differ...
<ul><li>Major criteria: </li></ul><ul><ul><li>At least 4 of the following - a major criterion in the skeletal system. </li...
<ul><li>Minor criteria: </li></ul><ul><ul><li>Pectus excavatum of moderate severity </li></ul></ul><ul><ul><li>Joint hyper...
<ul><li>Major criterion: </li></ul><ul><ul><li>Ectopia lentis </li></ul></ul><ul><li>Minor criteria: </li></ul><ul><ul><li...
<ul><li>Major criteria: </li></ul><ul><ul><li>Dilation of ascending aorta, with or without AR, and involving at least the ...
<ul><li>Pulmonary system </li></ul><ul><li>Major criteria: none </li></ul><ul><li>Minor criteria: </li></ul><ul><ul><li>Sp...
<ul><li>Dura </li></ul><ul><li>Major criterion: </li></ul><ul><ul><li>Lumbosacral dural ectasia (widening of the dural sac...
<ul><li>1 major system criteria – CVS </li></ul><ul><li>2 system  involvement – skeletal & skin </li></ul><ul><li>If not M...
<ul><li>Loeys-Dietz syndrome type I  </li></ul><ul><ul><li>Aortic aneurysm, Craniofacial anomalies </li></ul></ul><ul><ul>...
<ul><li>Beals Syndrome (CCA) – FBN2 </li></ul><ul><ul><li>Crumpled ears, Arachnodactyly, contractures, scoliosis </li></ul...
<ul><li>M itral valve prolapse,  A ortic dilation,  S kin, and  S keletal (MASS) phenotype  </li></ul><ul><ul><li>Many eva...
<ul><li>Familial Marfanlike (marfanoid) habitus </li></ul><ul><li>Familial Ectopia Lentis  </li></ul><ul><li>Weill-Marches...
<ul><li>MASS phenotype </li></ul>
<ul><li>Treatment of Mitral Valve Prolapse (MVP) </li></ul><ul><ul><li>No major symptoms –Echocardiographic monitoring. </...
 
<ul><li>Whatz new.. </li></ul><ul><li>AT1 receptor Signaling contributes to pathogenesis </li></ul><ul><li>ARBs –  </li></...
 
 
<ul><li>Cardiac evaluation in all Marfanoid patients </li></ul><ul><li>Diagnosis of MFS is made only by Ghent criteria </l...
 
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A Case of MASS phenotype

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A Case of MASS phenotype

  1. 1. Dr Prasanth Sankar Prof. E. Dhandapani’s Unit Stanley Medical College
  2. 2. <ul><li>Faiyaz </li></ul><ul><li>22y male D.O.A:7-3-10 ;9.30 pm </li></ul><ul><li>Chennai </li></ul><ul><ul><li>Admitted to toxiclogy ward with h/o </li></ul></ul><ul><ul><ul><li>Alcohol intoxication </li></ul></ul></ul><ul><ul><ul><li>Hypoglycemia – CBG - 41mg % </li></ul></ul></ul><ul><ul><li>No clinically relevant past history </li></ul></ul><ul><ul><li>Smoker, Alcoholic - 2yrs </li></ul></ul><ul><ul><li>Shopkeeper/labourer </li></ul></ul><ul><li>Treated with Inj. Thiamine, Dextrose, IVF </li></ul><ul><li>Shifted to male medical ward at 8pm on 8-3-10 </li></ul>
  3. 3. <ul><li>O/E </li></ul><ul><li>Patient conscious, oriented, cooperative </li></ul><ul><li>No pallor, icterus, cyanosis, clubbing, </li></ul><ul><li>No pedal edema, lymph nodes </li></ul><ul><li>Tobacco staining of tooth, caries tooth + </li></ul><ul><li>Temp -98.6 f </li></ul><ul><li>RR – 16/min </li></ul><ul><li>Pulse – 78/min regular, nl volume and character </li></ul><ul><li>BP – 120/80 mm hg </li></ul>
  4. 4. <ul><li>Anthropometry </li></ul><ul><li>Height – 180 cm </li></ul><ul><li>Weight – 60 kg </li></ul><ul><li>BMI – 18.50 </li></ul><ul><li>Head Circumference – 53 cm </li></ul><ul><li>Arm span – 192 cm </li></ul><ul><li>Arm span/Height ratio – 1.066 </li></ul><ul><li>Upper Segment – 80 cm </li></ul><ul><li>Lower Segment – 100 cm </li></ul><ul><li>US/LS ratio – 0.80 </li></ul>
  5. 9. <ul><li>CBC, RFT, RUE, LFT – WNL </li></ul><ul><li>Ecg – NSR, WNL </li></ul><ul><li>X –Ray Chest </li></ul><ul><li>X–Ray Pelvis-wnl </li></ul><ul><li>USG abdomen - WNL </li></ul>
  6. 10. <ul><li>Echo </li></ul><ul><ul><li>Bicuspid aortic valve </li></ul></ul><ul><ul><li>No AS/AR </li></ul></ul><ul><ul><li>Aortic annulus – 26mm </li></ul></ul><ul><ul><li>Aortic Sinus – 45 mm </li></ul></ul><ul><ul><li>Ascending Aorta – 36mm </li></ul></ul><ul><ul><li>Distal Aorta normal </li></ul></ul><ul><ul><li>No evidence of CoA </li></ul></ul><ul><ul><li>MVP-AML; no MR </li></ul></ul><ul><ul><li>Normal LV fn-EF – 67 % </li></ul></ul><ul><li>Adv- </li></ul><ul><ul><li>T. Atenolol 50 mg OD </li></ul></ul><ul><ul><li>Follow – up yearly </li></ul></ul>
  7. 11. <ul><li>Ophthalmology evaluation </li></ul><ul><ul><li>Lids, cornea, conjunctiva – normal </li></ul></ul><ul><ul><li>Ant chamber – normal depth </li></ul></ul><ul><ul><li>Iris, Pupil – normal </li></ul></ul><ul><ul><li>Lens normally placed; clear </li></ul></ul><ul><ul><li>F/s –disc, macula, vessels - normal </li></ul></ul><ul><ul><li>Visual acuity – 6/60 b/l </li></ul></ul>
  8. 12. <ul><li>DIAGNOSIS </li></ul><ul><ul><li>ALCOHOL INTOXICATION/ HYPOGLYCEMIA/ </li></ul></ul><ul><ul><li>MARFAN SYNDROME </li></ul></ul><ul><ul><li>or is it something else ?? </li></ul></ul>
  9. 13. <ul><li>AD- mutations in fbn1 gene on chromosome 15 </li></ul><ul><li>Abnormalities in TGF β -signaling – new culprit </li></ul><ul><li>New group of Marfan – related connective-tissue disorders - TGF β signalopathies </li></ul><ul><li>The diagnosis cannot be based on molecular analysis alone because </li></ul><ul><ul><li>molecular diagnosis is not generally available, </li></ul></ul><ul><ul><li>mutation detection is imperfect, and </li></ul></ul><ul><ul><li>not all FBN1 mutations are associated with MFS </li></ul></ul>
  10. 14. <ul><li>Index case: </li></ul><ul><ul><li>If the family/genetic history is not contributory, major criteria in ≥2 different organ systems and involvement of a third organ system. </li></ul></ul><ul><ul><li>If a mutation known to cause Marfan syndrome in others is detected, 1 major criterion in an organ system and involvement of a second organ system. </li></ul></ul><ul><li>Relative of an index case: </li></ul><ul><ul><li>Presence of a major criterion in the family history, 1 major criterion in an organ system, and involvement of a second organ system. </li></ul></ul>
  11. 15. <ul><li>Major criteria: </li></ul><ul><ul><li>At least 4 of the following - a major criterion in the skeletal system. </li></ul></ul><ul><ul><li>Pectus carinatum </li></ul></ul><ul><ul><li>Pectus excavatum requiring surgery </li></ul></ul><ul><ul><li>Reduced US-LS ratio or arm span–to–height ratio > 1.05 </li></ul></ul><ul><ul><li>Wrist and thumb signs </li></ul></ul><ul><ul><li>Scoliosis of > 20 ◦ or spondylolisthesis (displacement of vertebra, usually in lumbar spine) </li></ul></ul><ul><ul><li>Reduced extension at the elbows ( < 170◦) </li></ul></ul><ul><ul><li>Medial displacement of the medial malleolus causing pes planus </li></ul></ul><ul><ul><li>Protrusio acetabulae (protrusion of femoral head into the pelvis) of any degree (ascertained on radiographs) </li></ul></ul>
  12. 16. <ul><li>Minor criteria: </li></ul><ul><ul><li>Pectus excavatum of moderate severity </li></ul></ul><ul><ul><li>Joint hypermobility </li></ul></ul><ul><ul><li>Highly arched palate with crowding of teeth </li></ul></ul><ul><ul><li>Facial appearance </li></ul></ul><ul><ul><ul><li>dolichocephaly , </li></ul></ul></ul><ul><ul><ul><li>malar hypoplasia, </li></ul></ul></ul><ul><ul><ul><li>enophthalmos (deeply set eyes), </li></ul></ul></ul><ul><ul><ul><li>retrognathia (receding chin), </li></ul></ul></ul><ul><ul><ul><li>down-slanting palpebral fissures </li></ul></ul></ul><ul><li>For involvement of the skeletal system, at least </li></ul><ul><ul><li>2 features contributing to major criteria, </li></ul></ul><ul><ul><li>1 major criterion and 2 minor criteria must be present. </li></ul></ul>
  13. 17. <ul><li>Major criterion: </li></ul><ul><ul><li>Ectopia lentis </li></ul></ul><ul><li>Minor criteria: </li></ul><ul><ul><li>Abnormally flat cornea </li></ul></ul><ul><ul><li>Increased axial length of globe (myopia) </li></ul></ul><ul><ul><li>Hypoplastic iris or hypoplastic ciliary muscle causing decreased miosis </li></ul></ul><ul><li>For involvement of the ocular system, at least 2 of the minor criteria must be present. </li></ul>
  14. 18. <ul><li>Major criteria: </li></ul><ul><ul><li>Dilation of ascending aorta, with or without AR, and involving at least the sinuses of Valsalva </li></ul></ul><ul><ul><li>Dissection of the ascending aorta </li></ul></ul><ul><li>Minor criteria: </li></ul><ul><ul><li>MVP with or without MR </li></ul></ul><ul><ul><li>Dilatation of the main PA, in the absence of valvular or peripheral PS or any other obvious cause, <age 40 </li></ul></ul><ul><ul><li>Calcification of the mitral annulus <age 40 </li></ul></ul><ul><ul><li>Dilatation or dissection of the descending thoracic or abdominal aorta <age 50 </li></ul></ul><ul><li>For involvement of the cardiovascular system, only 1 of the minor criteria must be present. </li></ul>
  15. 19. <ul><li>Pulmonary system </li></ul><ul><li>Major criteria: none </li></ul><ul><li>Minor criteria: </li></ul><ul><ul><li>Spontaneous pneumothorax </li></ul></ul><ul><ul><li>Apical blebs </li></ul></ul><ul><li>For involvement of pulmonary system, only 1 of the minor criteria must be present </li></ul><ul><li>Skin and integument </li></ul><ul><li>Major criteria: none </li></ul><ul><li>Minor criteria: </li></ul><ul><ul><li>Striae atrophicae (stretch marks) without marked weight gain, pregnancy, or repetitive stress </li></ul></ul><ul><ul><li>Recurrent or incisional herniae </li></ul></ul><ul><li>For involvement of skin and integument, only 1 of the minor criteria must be present </li></ul>
  16. 20. <ul><li>Dura </li></ul><ul><li>Major criterion: </li></ul><ul><ul><li>Lumbosacral dural ectasia (widening of the dural sac) </li></ul></ul><ul><li>Minor criteria: none </li></ul><ul><li>Family/genetic history </li></ul><ul><li>Major criteria: </li></ul><ul><ul><li>Having a parent, child, or sibling who meets these diagnostic criteria independently </li></ul></ul><ul><ul><li>Presence of a mutation in FBN1 that is known to cause MFS </li></ul></ul><ul><ul><li>Presence of a haplotype around FBN1 , inherited by descent, associated with unequivocally diagnosed MFS in the family </li></ul></ul><ul><li>Minor criteria: none </li></ul>
  17. 21. <ul><li>1 major system criteria – CVS </li></ul><ul><li>2 system involvement – skeletal & skin </li></ul><ul><li>If not Marfan, then what?? </li></ul>
  18. 22. <ul><li>Loeys-Dietz syndrome type I </li></ul><ul><ul><li>Aortic aneurysm, Craniofacial anomalies </li></ul></ul><ul><ul><li>Absence of long bone overgrowth or lens dislocation </li></ul></ul><ul><li>Loeys-Dietz syndrome type II </li></ul><ul><ul><li>Reminiscent of vascular EDS. </li></ul></ul><ul><ul><li>Uterine rupture, peripartal bleedings, skin bleeds </li></ul></ul><ul><ul><li>Arterial aneurysm/dissections throughout arterial circulation. </li></ul></ul><ul><li>TGFβR1/2 mutations - mean age at death of 26.1 y. </li></ul><ul><li>Aortic dissections at smaller aortic dimensions (<40 mm) </li></ul><ul><li>High incidence of pregnancy-related complications. </li></ul>
  19. 23. <ul><li>Beals Syndrome (CCA) – FBN2 </li></ul><ul><ul><li>Crumpled ears, Arachnodactyly, contractures, scoliosis </li></ul></ul><ul><li>Bicuspid Aortic Valve </li></ul><ul><ul><li>Most common cardiac malformation </li></ul></ul><ul><ul><li>Aortic root dilation that often occurs above sinuses. </li></ul></ul><ul><li>Familial thoracic aortic aneurysm/dissection </li></ul><ul><ul><li>Progressive; no or minor systemic involvement </li></ul></ul><ul><ul><li>FBN1/ TGFβR2 mutations identified </li></ul></ul><ul><li>Homocystinuria </li></ul><ul><ul><li>Ectopia lentis, long bone overgrowth, mental retardation. </li></ul></ul><ul><ul><li>Thromboembolism and CAD without root dilatation. </li></ul></ul><ul><ul><li>Elevated homocystine in urine or plasma. </li></ul></ul>
  20. 24. <ul><li>M itral valve prolapse, A ortic dilation, S kin, and S keletal (MASS) phenotype </li></ul><ul><ul><li>Many evaluated for Marfan syndrome who do not meet diagnostic criteria, have a varying constellation of </li></ul></ul><ul><ul><ul><li>M ITRAL VALVE PROLAPSE; M YOPIA; </li></ul></ul></ul><ul><ul><ul><li>A ORTIC ROOT DILATION-MILD, NONPROGRESSIVE </li></ul></ul></ul><ul><ul><ul><li>S KELETAL AND </li></ul></ul></ul><ul><ul><ul><li>S KIN FEATURES. </li></ul></ul></ul><ul><ul><li>This phenotype may segregate as a dominant trait and remain stable over time. </li></ul></ul><ul><ul><li>In some instances, FBN1 mutations have been identified.  </li></ul></ul>
  21. 25. <ul><li>Familial Marfanlike (marfanoid) habitus </li></ul><ul><li>Familial Ectopia Lentis </li></ul><ul><li>Weill-Marchesani syndrome </li></ul><ul><li>Stickler syndrome </li></ul><ul><li>Shprintzen-Goldberg syndrome </li></ul><ul><li>Ehlers-Danlos Syndrome </li></ul><ul><li>Familial aortic dissection </li></ul><ul><li>Familial arachnodactyly </li></ul><ul><li>Familial mitral valve prolapse syndrome </li></ul><ul><li>XYY syndrome </li></ul><ul><li>… </li></ul>
  22. 26. <ul><li>MASS phenotype </li></ul>
  23. 27. <ul><li>Treatment of Mitral Valve Prolapse (MVP) </li></ul><ul><ul><li>No major symptoms –Echocardiographic monitoring. </li></ul></ul><ul><ul><li>IE prophylaxis, Beta-blockers. </li></ul></ul><ul><ul><li>Severe symptoms- MVP/MR – surgery. </li></ul></ul><ul><li>Treatment of the Aortic Aneurysm </li></ul><ul><ul><li>Ascending aorta - upper limits of normal. </li></ul></ul><ul><ul><li>Progression of aneurysm or dissection unusual </li></ul></ul><ul><ul><li>Yearly echocardiograpic monitoring </li></ul></ul><ul><li>Treatment of Skeletal Conditions </li></ul><ul><ul><li>Scoliosis – surgery if curve is 40-50 degrees or greater </li></ul></ul><ul><ul><li>Annual spinal exams if there is a significant curvature or pain </li></ul></ul><ul><ul><li>Chest Wall Deformities – severe pectus excavatum – surgery </li></ul></ul><ul><li>Treatment of the Skin </li></ul><ul><ul><li>Stretch marks require no medical treatment </li></ul></ul>
  24. 29. <ul><li>Whatz new.. </li></ul><ul><li>AT1 receptor Signaling contributes to pathogenesis </li></ul><ul><li>ARBs – </li></ul><ul><ul><li> expression of TGFβ ligands and their receptors </li></ul></ul><ul><ul><li>Limit production of activators of TGFβ </li></ul></ul><ul><li>In murine models of Marfan syndrome ARBs </li></ul><ul><ul><li>Prevent pathologic aortic root growth. </li></ul></ul><ul><ul><li>Normalize aortic wall architecture and thickness. </li></ul></ul><ul><ul><li>Improve non- cardiovascular manifestations such as pulmonary and skeletal muscle pathology </li></ul></ul>
  25. 32. <ul><li>Cardiac evaluation in all Marfanoid patients </li></ul><ul><li>Diagnosis of MFS is made only by Ghent criteria </li></ul><ul><li>Progession of dilatation is rare in MASS phenotype </li></ul><ul><li>Increased activation of and signaling by TGFβ. </li></ul><ul><li>Lifelong Beta-blockers </li></ul><ul><li>ARBs– future perspective. </li></ul><ul><li>Moderation in activity, lifestyle, Pregnancy </li></ul><ul><li>Elective repair if aortic root ≥ 5 cm in adults. </li></ul><ul><li>IE prophylaxis </li></ul>

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