GENETICS RELEVANTTOANAESTHESIA
Dr. MRIDUL M. PANDITRAOConsultantDepartment of AnesthesiologyRand Memorial HospitalFREEPORT, BAHAMAS
Introduction• “ All humans are born Equal ”• Irrespective of our Color, Creed, & Race, we allshare 99.9% genetic material....
Introduction• Via functioning of variousenzymes, neurotransmitters / modulators• Polymorphisms: May occur at single or mul...
Introduction• Some early examples, which made us aware: Prolonged apnea after Succynil Choline Thiopentone induced Porph...
Types of Genetic disorders• Single gene disorders : Mendelian/ monogenic• Polygenic disorders• Multi Factorial Problems• C...
Single gene disorders• Autosomal : Achodroplasia• Autosomal Recessive: Sickle Celldisease, Cystic Fibrosis• X linked Disor...
Polygenic disordersBy combination of 2 or more genese.g.• Coronary Artery Disease• Diabetes Mellitus• Hypertension• Peptic...
Multi Factorial ProblemsCombination of Polygenic and environmentalfactorse.g.• Asthma• Autism• Mental Retardation• Cleft P...
Chromosomal Abnormalities• Due to abnormalities of Number or structure ofchromosomes• Chromosomal sequence – deletions, in...
Mitochondrial Mutations• Exclusively through mitochondrial DNA• Mitochondria are kept in egg cells duringfertilization• So...
Genetics and Anaesthesia• What do genetic variations do toPre-operative assessment/ Preparation,anaesthetic/ Intra-operati...
Influence of Genetic Expression/Disorders on Anaesthetic Management• Developmental anomalies• Affect anaesthetic managemen...
Problems• Airway Abnormailities / difficulties• Micrognathia and relative macroglossa• Congenital / developmental cardiac ...
Airway Abnormalities/difficulties• Major concern for Anaesthesiologist• Anatomical/ developmental defects (Cranio-facial)•...
Micrognathia andrelative macroglossa• Difficult airway: intra as well as post –operativee.g. Achondrogenesis I & II Pier...
Congenital/ developmentalcardiac defects• Second most common set of anomalies• Usually in association with otherdevelopmen...
Congenital/ developmentalcardiac defects• Antley- Bexeler• Klippel Feil, PKU, Fryn’s• Goldenhar• Trisomies 8 & 9• Turner’s...
Renal/ Hepatic• Rarely singly, always in association• Always complicate post-operative mgt.e.g. Alpha Thallasemia Antley...
CNS/ Mental Retardation• Mental retardation, a common and classicalfeature in syndromes: Down’s Acrodystosis Alpha thal...
Turner’s Syndrome• Genotype: XO, Phenotype: Female• Broad chested, Web necked, Widely placednipples• Female Genital tract ...
Trisomies: 8, 8 mosaic, 9, 9 mosaic,13, 18, & 21• Variety of presentations• Common to all : Growth and Mental deficiencies...
Trisomies• Anaesthetic consideration:• Complete haematological work up,• Radiological profile• Anticipated difficult intub...
Sickle Cell Disease• Autosomal recessive, haemoglobinopathy• Altered RBC shape & increased viscosity ofblood secondary to ...
Goldenhar Syndrome(Hemifacial microsomia)• Defects in Facial structures• Mostly in first and second branchial arches• Vert...
Goldenhar Syndrome( Hemifacial microsomia)• NMBDs to be avoided• Smaller doses of Anti-cholinergics to beused• Post-operat...
Klippel- Feil Syndrome• Extremely short neck• Fusion of Cervical vertebrae• Other vertebral and cardiac abnormalities• Air...
Marfan’s Syndrome• Tall stature, archnodactyly &hyperextensibility• Aortic Dilatation and subluxation of Lens• Scoliosis a...
Multiple Neuroma syndrome(MEN Type II)• As in Marfans; Tall stature with Multipleneuromata of Facial structures ;• lips, t...
Poly-cystic kidney Disease• Auto-somal dominant• Presents in 5th decade of life,• Cysts inKidney, Lungs, liver, pancreas, ...
Polycystic Kidneys
Osteogenesis imperfecta Type I &II, Arthrogryposis Multiplex congenitaand others• Autosomal Dominant• Defect in Type I col...
Osteogenesis imperfectaArthrogryposis Multiplex congenita
Osteogenesis imperfecta Type I &II, Arthrogryposis Multiplexcongenita and others• Pre-op airway , vertebro-skeletalassessm...
Noonan syndrome• Short stature, Web neck & pectus excavatus• Micrognathia, Cranio-facial• Pulmonary stenosis and cardiac• ...
Pierre Robin Syndrome• Micrognathia, Macroglossa/ glossoptosis• Cleft lip/ palate• May have cardiac defects• Airway diffic...
Prader Willi• Pronounced structural, truncal obesity• Short stature, scoliosis• Hypogonadism, mental defects• Cardio-respi...
Prader Willi
Neurofibromatosis• Autosomal dominant, Multiple neufibromata• Not only in neuraxis, but in lx/ Nasophx• May have pulm. Fib...
Neurofibromatosis• Von Recklinghausen’s : Multipleneurofibromata, café au lait spots,• Airway major problem• Inhalational ...
Achondrodysplasias• Short limbed dwaqrfism, 1:15000-40000• Autosomal Dominant, defect in fibroblastgrowth factor receptor ...
Thalassemias α &β• Classical X linked recessive disorders• Severe form of mental retardation• Typical cranio-facial defect...
TEF/ Esophagial Atresia/VATER• Vertebral Anomalies, Traheo Esophgial Fitula& radial dysplasia: singly or as Trisomy 18• La...
Cystic Fibrosis• Autosomal recessive, mainly in Caucasian race• Chromosome 7 : gene mutation• New born; meconeum obstructi...
Anaesthesia on Genetic Make up• Controversial, delicate yet important topic• No clear opinion: Mutagenecity/ teratogenecit...
Recent: Pharmacogenomics• Defn.• Synchrony of two words: pharmacology andgenomics• intersection of pharmaceuticals and gen...
Pharmacogenomics: projectedbenefits• Better, safer, trial-error free drugs• More appropriate methods for dosages• Advanced...
Pharmacogenomics• Cytochrome P 450 genes used to screen/monitor patients• Still in the trial phases
Conclusion• Advances in genetics: opening newvistas,horizons of knowledge andunderstanding• Anaesthesiologists: peri-op ph...
Mridul panditrao genetics relevant to anesthesia
Mridul panditrao genetics relevant to anesthesia
Mridul panditrao genetics relevant to anesthesia
Mridul panditrao genetics relevant to anesthesia
Mridul panditrao genetics relevant to anesthesia
Mridul panditrao genetics relevant to anesthesia
Mridul panditrao genetics relevant to anesthesia
Mridul panditrao genetics relevant to anesthesia
Mridul panditrao genetics relevant to anesthesia
Mridul panditrao genetics relevant to anesthesia
Mridul panditrao genetics relevant to anesthesia
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Mridul panditrao genetics relevant to anesthesia

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Prof Mridul Panditrao puts forward his ideas about the correlation between Genetics and Anesthesia, the impact of them on each other and the concerns of the Anesthesiologists in dealing with these patients!

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Mridul panditrao genetics relevant to anesthesia

  1. 1. GENETICS RELEVANTTOANAESTHESIA
  2. 2. Dr. MRIDUL M. PANDITRAOConsultantDepartment of AnesthesiologyRand Memorial HospitalFREEPORT, BAHAMAS
  3. 3. Introduction• “ All humans are born Equal ”• Irrespective of our Color, Creed, & Race, we allshare 99.9% genetic material.• 0.1% variability: Polymorphisms• Polymorphisms differentiate us• Phenotypically these are expressed asgenetically transmitted diseases• Polymorphisms play role pharmacodynamically/kinetically through biologically active substances
  4. 4. Introduction• Via functioning of variousenzymes, neurotransmitters / modulators• Polymorphisms: May occur at single or multiplenucleotides , as insertions or deletions• May be of importance for anaesthestic practice• A wide spectrum From mild influence to lifethreatening consequences• Well acquainting by anaesthesiologist is must
  5. 5. Introduction• Some early examples, which made us aware: Prolonged apnea after Succynil Choline Thiopentone induced Porphyria Malignant Hyperthermia• In addition to Certain Factors like age, sexetc, genetic profile is also assuming utmostimportance
  6. 6. Types of Genetic disorders• Single gene disorders : Mendelian/ monogenic• Polygenic disorders• Multi Factorial Problems• Chromosomal Abnormalities
  7. 7. Single gene disorders• Autosomal : Achodroplasia• Autosomal Recessive: Sickle Celldisease, Cystic Fibrosis• X linked Disorders: Mother to offspringe.g. hemophilia• Y linked Disorders: father to son
  8. 8. Polygenic disordersBy combination of 2 or more genese.g.• Coronary Artery Disease• Diabetes Mellitus• Hypertension• Peptic Ulcer
  9. 9. Multi Factorial ProblemsCombination of Polygenic and environmentalfactorse.g.• Asthma• Autism• Mental Retardation• Cleft Palate
  10. 10. Chromosomal Abnormalities• Due to abnormalities of Number or structure ofchromosomes• Chromosomal sequence – deletions, inversionsor translocationse.g.• 21 Trisomy- Down’s Syndrome• Turner’s Syndrome
  11. 11. Mitochondrial Mutations• Exclusively through mitochondrial DNA• Mitochondria are kept in egg cells duringfertilization• So always inherited from female patterne.g.• Leber’s Hereditary Optic neuropathy• MERRF (type of epilepsy)
  12. 12. Genetics and Anaesthesia• What do genetic variations do toPre-operative assessment/ Preparation,anaesthetic/ Intra-operative management &Post operative Care• How do the anaesthtic agents/ managementinfluence the genetic make up of the humans
  13. 13. Influence of Genetic Expression/Disorders on Anaesthetic Management• Developmental anomalies• Affect anaesthetic management• Anatomic / physiologic changes• Challenges frompharmacological, biochemical, structural, functional and procedural point of view• Specific problems must be considered
  14. 14. Problems• Airway Abnormailities / difficulties• Micrognathia and relative macroglossa• Congenital / developmental cardiac defects• Renal / Hepatic• CNS / Mental Retardation
  15. 15. Airway Abnormalities/difficulties• Major concern for Anaesthesiologist• Anatomical/ developmental defects (Cranio-facial)• Anomalies of airwaye.g. Cleft Lip/ palate Developmental Tumors ; Neuromas Choanal atresia Tracheo-oesophagial fistula
  16. 16. Micrognathia andrelative macroglossa• Difficult airway: intra as well as post –operativee.g. Achondrogenesis I & II Pierre- Robin WAGR Noonan’s, Fryn’s Brachio-Occulo- Facial
  17. 17. Congenital/ developmentalcardiac defects• Second most common set of anomalies• Usually in association with otherdevelopmental anomaliesespecially Cranio-facial, vertebro-skeletal, thoracic many examples
  18. 18. Congenital/ developmentalcardiac defects• Antley- Bexeler• Klippel Feil, PKU, Fryn’s• Goldenhar• Trisomies 8 & 9• Turner’s, WAGR• Foetal diphenyl Hydantoin syndrome
  19. 19. Renal/ Hepatic• Rarely singly, always in association• Always complicate post-operative mgt.e.g. Alpha Thallasemia Antley-Bixler BOF, Foetal Diphenyl Gopldenhar, Klippel-Feil Turner, Miller, WAGR
  20. 20. CNS/ Mental Retardation• Mental retardation, a common and classicalfeature in syndromes: Down’s Acrodystosis Alpha thallasemia Watson, Angelman’s, Cowden’s, Costello’s
  21. 21. Turner’s Syndrome• Genotype: XO, Phenotype: Female• Broad chested, Web necked, Widely placednipples• Female Genital tract abnormalities• Anaesthetic Cosiderations : coexistance ofMicrognathia, Coarctation Of Aorta, Horseshoe Kidney and Vertebro- thoracic anomalies
  22. 22. Trisomies: 8, 8 mosaic, 9, 9 mosaic,13, 18, & 21• Variety of presentations• Common to all : Growth and Mental deficiencies/ retardation• Abnormal Facial features: difficult Airway• Cleft Lip/Palate, Micrognathia and Macroglossa• Cardio-thoracic defects,• Rarely, Cardiac and renal defects
  23. 23. Trisomies• Anaesthetic consideration:• Complete haematological work up,• Radiological profile• Anticipated difficult intubation• Difficulties of co-existing other systemanomalies• Post-op speciallized care
  24. 24. Sickle Cell Disease• Autosomal recessive, haemoglobinopathy• Altered RBC shape & increased viscosity ofblood secondary to hypoxemia• Anaesthesia: Must avoidHypoxia, Hypercapnea, dehydration,hypothermia and acidosisG.A is preferred technique
  25. 25. Goldenhar Syndrome(Hemifacial microsomia)• Defects in Facial structures• Mostly in first and second branchial arches• Vertebral and cardiac defects• Anaesthetic consideration• Pre-op: evaluation of upper and lower airway• Pulmonary, Hepatic and renal function tests• Intra op: I.V. Induction preferred ( inhalationalavoided)
  26. 26. Goldenhar Syndrome( Hemifacial microsomia)• NMBDs to be avoided• Smaller doses of Anti-cholinergics to beused• Post-operative care absolutely essential
  27. 27. Klippel- Feil Syndrome• Extremely short neck• Fusion of Cervical vertebrae• Other vertebral and cardiac abnormalities• Airway and neuraxial Block difficulties tobe anticipated
  28. 28. Marfan’s Syndrome• Tall stature, archnodactyly &hyperextensibility• Aortic Dilatation and subluxation of Lens• Scoliosis and Cleft Lip• Hypertensive response to Laryngoscopy• use of Beta Blockers recommended
  29. 29. Multiple Neuroma syndrome(MEN Type II)• As in Marfans; Tall stature with Multipleneuromata of Facial structures ;• lips, tongue, ganglia, oral & pharyngealstructures• Medullary Ca. Thyroid, Kypho-scoliosis/lordosis• Difficult airway• Phaeochromocytoma
  30. 30. Poly-cystic kidney Disease• Auto-somal dominant• Presents in 5th decade of life,• Cysts inKidney, Lungs, liver, pancreas, spleen, thyroidetc.• Leading to slow but progressive failure oforgans involved• ESRDS, pneumothorax, Hypertension• Other systemic problems
  31. 31. Polycystic Kidneys
  32. 32. Osteogenesis imperfecta Type I &II, Arthrogryposis Multiplex congenitaand others• Autosomal Dominant• Defect in Type I collagen synthesis• Resulting in defective connective tissuesynthesis and bone formation• Fragile, abnormal bones, growth and dentalanomalies• Blue sclera• Easy brusing and vertebral anomalies
  33. 33. Osteogenesis imperfectaArthrogryposis Multiplex congenita
  34. 34. Osteogenesis imperfecta Type I &II, Arthrogryposis Multiplexcongenita and others• Pre-op airway , vertebro-skeletalassessment• Anticipated difficult airway• Intra-op careful handling• Post-op ventilatory support?
  35. 35. Noonan syndrome• Short stature, Web neck & pectus excavatus• Micrognathia, Cranio-facial• Pulmonary stenosis and cardiac• At very high risk of developing MalignantHyperpyrexia• GA to be avoided• Spinal is the technique of choice
  36. 36. Pierre Robin Syndrome• Micrognathia, Macroglossa/ glossoptosis• Cleft lip/ palate• May have cardiac defects• Airway difficulties anticipated• Inhalational induction
  37. 37. Prader Willi• Pronounced structural, truncal obesity• Short stature, scoliosis• Hypogonadism, mental defects• Cardio-respiratory problems:arrythmias, conduction defects, COPD• Convulsions• Diabetes
  38. 38. Prader Willi
  39. 39. Neurofibromatosis• Autosomal dominant, Multiple neufibromata• Not only in neuraxis, but in lx/ Nasophx• May have pulm. Fibrosis, Pheochromocytoma• Renal artery stenosis & hypertension• Carcinoids• Type I: von Recklinghausen• Type II: Bilateral Acoustic Neurofibroma
  40. 40. Neurofibromatosis• Von Recklinghausen’s : Multipleneurofibromata, café au lait spots,• Airway major problem• Inhalational induction recommended• Pulm fibrosis; complicates, Higher FiO2,• Enhanced sensitivity to NMBDs.
  41. 41. Achondrodysplasias• Short limbed dwaqrfism, 1:15000-40000• Autosomal Dominant, defect in fibroblastgrowth factor receptor 3 gene(FGFR3)• Short limbs, saddle nose, ant. epiglottis, smallchest, Pulmonary hypoplasia and Lordosis• Spinal, renal, anomalies• High anxiety and hydrocephalous• Extensive Pre-op and intra op care
  42. 42. Thalassemias α &β• Classical X linked recessive disorders• Severe form of mental retardation• Typical cranio-facial defects, macroglossa• CNS, Vertebral and genital anomalies• Renal agenesis• & haemolytic anaemia•
  43. 43. TEF/ Esophagial Atresia/VATER• Vertebral Anomalies, Traheo Esophgial Fitula& radial dysplasia: singly or as Trisomy 18• Laryngeal stenosis, pulmonary & Ribdefects, limb deficiencies,• Hemorrhages and hyperbilirubinemia• Detailed Radiological workup, systemicevaluation
  44. 44. Cystic Fibrosis• Autosomal recessive, mainly in Caucasian race• Chromosome 7 : gene mutation• New born; meconeum obstruction in 1st 24 hrs.• GI malabsorption, recurrent Pulm infection• Failure to thrive, late puberty, infertility• Coagulation defects : Vit K absorption deficient• Thorough work up
  45. 45. Anaesthesia on Genetic Make up• Controversial, delicate yet important topic• No clear opinion: Mutagenecity/ teratogenecity• Nitrous Oxide controversy• Recent ‘evidence’:• Prevention and precaution , prudent decisionmaking imperative
  46. 46. Recent: Pharmacogenomics• Defn.• Synchrony of two words: pharmacology andgenomics• intersection of pharmaceuticals and genetics• Of great importance from anaesthesia• Customization as per pt’s genetic makeup, specific conditions• tailor made applicability of anaesthesia
  47. 47. Pharmacogenomics: projectedbenefits• Better, safer, trial-error free drugs• More appropriate methods for dosages• Advanced screening for diseases• Better vaccines• Faster drug discovery and approval process
  48. 48. Pharmacogenomics• Cytochrome P 450 genes used to screen/monitor patients• Still in the trial phases
  49. 49. Conclusion• Advances in genetics: opening newvistas,horizons of knowledge andunderstanding• Anaesthesiologists: peri-op physicians• More and more challenges• This is Future

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