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!

1. GENETICS RELEVANT
TO
ANAESTHESIA

2. Dr. MRIDUL M. PANDITRAO
Consultant
Department of Anesthesiology
Rand Memorial Hospital
FREEPORT, BAHAMAS

3. Introduction
• “ All humans are born Equal ”
• Irrespective of our Color, Creed, & Race, we all
share 99.9% genetic material.
• 0.1% variability: Polymorphisms
• Polymorphisms differentiate us
• Phenotypically these are expressed as
genetically transmitted diseases
• Polymorphisms play role pharmacodynamically/
kinetically through biologically active substances

4. Introduction
• Via functioning of various
enzymes, neurotransmitters / modulators
• Polymorphisms: May occur at single or multiple
nucleotides , as insertions or deletions
• May be of importance for anaesthestic practice
• A wide spectrum From mild influence to life
threatening consequences
• Well acquainting by anaesthesiologist is must

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, sex
etc, genetic profile is also assuming utmost
importance

6. Types of Genetic disorders
• Single gene disorders : Mendelian/ monogenic
• Polygenic disorders
• Multi Factorial Problems
• Chromosomal Abnormalities

7. Single gene disorders
• Autosomal : Achodroplasia
• Autosomal Recessive: Sickle Cell
disease, Cystic Fibrosis
• X linked Disorders: Mother to offspring
e.g. hemophilia
• Y linked Disorders: father to son

8. Polygenic disorders
By combination of 2 or more genes
e.g.
• Coronary Artery Disease
• Diabetes Mellitus
• Hypertension
• Peptic Ulcer

9. Multi Factorial Problems
Combination of Polygenic and environmental
factors
e.g.
• Asthma
• Autism
• Mental Retardation
• Cleft Palate

10. Chromosomal Abnormalities
• Due to abnormalities of Number or structure of
chromosomes
• Chromosomal sequence – deletions, inversions
or translocations
e.g.
• 21 Trisomy- Down’s Syndrome
• Turner’s Syndrome

11. Mitochondrial Mutations
• Exclusively through mitochondrial DNA
• Mitochondria are kept in egg cells during
fertilization
• So always inherited from female pattern
e.g.
• Leber’s Hereditary Optic neuropathy
• MERRF (type of epilepsy)

12. Genetics and Anaesthesia
• What do genetic variations do to
Pre-operative assessment/ Preparation,
anaesthetic/ Intra-operative management &
Post operative Care
• How do the anaesthtic agents/ management
influence the genetic make up of the humans

13. Influence of Genetic Expression/
Disorders on Anaesthetic Management
• Developmental anomalies
• Affect anaesthetic management
• Anatomic / physiologic changes
• Challenges from
pharmacological, biochemical, structural, func
tional and procedural point of view
• Specific problems must be considered

14. Problems
• Airway Abnormailities / difficulties
• Micrognathia and relative macroglossa
• Congenital / developmental cardiac defects
• Renal / Hepatic
• CNS / Mental Retardation

15. Airway Abnormalities/difficulties
• Major concern for Anaesthesiologist
• Anatomical/ developmental defects (Cranio-facial)
• Anomalies of airway
e.g.
 Cleft Lip/ palate
 Developmental Tumors ; Neuromas
 Choanal atresia
 Tracheo-oesophagial fistula

16. Micrognathia and
relative macroglossa
• Difficult airway: intra as well as post –operative
e.g.
 Achondrogenesis I & II
 Pierre- Robin
 WAGR
 Noonan’s, Fryn’s
 Brachio-Occulo- Facial

17. Congenital/ developmental
cardiac defects
• Second most common set of anomalies
• Usually in association with other
developmental anomalies
especially
 Cranio-facial, vertebro-skeletal, thoracic
 many examples

18. Congenital/ developmental
cardiac defects
• Antley- Bexeler
• Klippel Feil, PKU, Fryn’s
• Goldenhar
• Trisomies 8 & 9
• Turner’s, WAGR
• Foetal diphenyl Hydantoin syndrome

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. CNS/ Mental Retardation
• Mental retardation, a common and classical
feature in syndromes:
 Down’s
 Acrodystosis
 Alpha thallasemia
 Watson, Angelman’s,
 Cowden’s, Costello’s

21. Turner’s Syndrome
• Genotype: XO, Phenotype: Female
• Broad chested, Web necked, Widely placed
nipples
• Female Genital tract abnormalities
• Anaesthetic Cosiderations : coexistance of
Micrognathia, Coarctation Of Aorta, Horse
shoe Kidney and Vertebro- thoracic anomalies

23. 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

24. Trisomies
• Anaesthetic consideration:
• Complete haematological work up,
• Radiological profile
• Anticipated difficult intubation
• Difficulties of co-existing other system
anomalies
• Post-op speciallized care

25. Sickle Cell Disease
• Autosomal recessive, haemoglobinopathy
• Altered RBC shape & increased viscosity of
blood secondary to hypoxemia
• Anaesthesia: Must avoid
Hypoxia, Hypercapnea, dehydration,
hypothermia and acidosis
G.A is preferred technique

26. 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 ( inhalational
avoided)

28. Goldenhar Syndrome
( Hemifacial microsomia)
• NMBDs to be avoided
• Smaller doses of Anti-cholinergics to be
used
• Post-operative care absolutely essential

29. Klippel- Feil Syndrome
• Extremely short neck
• Fusion of Cervical vertebrae
• Other vertebral and cardiac abnormalities
• Airway and neuraxial Block difficulties to
be anticipated

31. 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

33. Multiple Neuroma syndrome
(MEN Type II)
• As in Marfans; Tall stature with Multiple
neuromata of Facial structures ;
• lips, tongue, ganglia, oral & pharyngeal
structures
• Medullary Ca. Thyroid, Kypho-scoliosis/lordosis
• Difficult airway
• Phaeochromocytoma

35. Poly-cystic kidney Disease
• Auto-somal dominant
• Presents in 5th decade of life,
• Cysts in
Kidney, Lungs, liver, pancreas, spleen, thyroid
etc.
• Leading to slow but progressive failure of
organs involved
• ESRDS, pneumothorax, Hypertension
• Other systemic problems

36. Polycystic Kidneys

37. Osteogenesis imperfecta Type I &
II, Arthrogryposis Multiplex congenita
and others
• Autosomal Dominant
• Defect in Type I collagen synthesis
• Resulting in defective connective tissue
synthesis and bone formation
• Fragile, abnormal bones, growth and dental
anomalies
• Blue sclera
• Easy brusing and vertebral anomalies

38. Osteogenesis imperfecta
Arthrogryposis Multiplex congenita

39. Osteogenesis imperfecta Type I &
II, Arthrogryposis Multiplex
congenita and others
• Pre-op airway , vertebro-skeletal
assessment
• Anticipated difficult airway
• Intra-op careful handling
• Post-op ventilatory support?

40. Noonan syndrome
• Short stature, Web neck & pectus excavatus
• Micrognathia, Cranio-facial
• Pulmonary stenosis and cardiac
• At very high risk of developing Malignant
Hyperpyrexia
• GA to be avoided
• Spinal is the technique of choice

42. Pierre Robin Syndrome
• Micrognathia, Macroglossa/ glossoptosis
• Cleft lip/ palate
• May have cardiac defects
• Airway difficulties anticipated
• Inhalational induction

44. Prader Willi
• Pronounced structural, truncal obesity
• Short stature, scoliosis
• Hypogonadism, mental defects
• Cardio-respiratory problems:
arrythmias, conduction defects, COPD
• Convulsions
• Diabetes

45. Prader Willi

46. 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

48. Neurofibromatosis
• Von Recklinghausen’s : Multiple
neurofibromata, café au lait spots,
• Airway major problem
• Inhalational induction recommended
• Pulm fibrosis; complicates, Higher FiO2,
• Enhanced sensitivity to NMBDs.

49. Achondrodysplasias
• Short limbed dwaqrfism, 1:15000-40000
• Autosomal Dominant, defect in fibroblast
growth factor receptor 3 gene(FGFR3)
• Short limbs, saddle nose, ant. epiglottis, small
chest, Pulmonary hypoplasia and Lordosis
• Spinal, renal, anomalies
• High anxiety and hydrocephalous
• Extensive Pre-op and intra op care

51. 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
•

53. TEF/ Esophagial Atresia/VATER
• Vertebral Anomalies, Traheo Esophgial Fitula
& radial dysplasia: singly or as Trisomy 18
• Laryngeal stenosis, pulmonary & Rib
defects, limb deficiencies,
• Hemorrhages and hyperbilirubinemia
• Detailed Radiological workup, systemic
evaluation

54. 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

55. Anaesthesia on Genetic Make up
• Controversial, delicate yet important topic
• No clear opinion: Mutagenecity/ teratogenecity
• Nitrous Oxide controversy
• Recent ‘evidence’:
• Prevention and precaution , prudent decision
making imperative

56. Recent: Pharmacogenomics
• Defn.
• Synchrony of two words: pharmacology and
genomics
• intersection of pharmaceuticals and genetics
• Of great importance from anaesthesia
• Customization as per pt’s genetic make
up, specific conditions
• tailor made applicability of anaesthesia

57. Pharmacogenomics: projected
benefits
• Better, safer, trial-error free drugs
• More appropriate methods for dosages
• Advanced screening for diseases
• Better vaccines
• Faster drug discovery and approval process

58. Pharmacogenomics
• Cytochrome P 450 genes used to screen/
monitor patients
• Still in the trial phases

59. Conclusion
• Advances in genetics: opening new
vistas,horizons of knowledge and
understanding
• Anaesthesiologists: peri-op physicians
• More and more challenges
• This is Future