Anesthesia and Analgesia
Volume 91 Number 4 October 2000
Copyright 2000 Association for Professionals in Infection Control and Epidemiology, Inc.



Specific Genetic Diseases at Risk for Sedation/Anesthesia Complications

Merlin G. Butler MD, PhD, FACMG
Blaine G. Hayes BS
Melanie M. Hathaway BA, BS
Michael L. Begleiter MS, CGC

Section of Medical Genetics and Molecular Medicine, Children's Mercy Hospitals and Clinics, Kansas City, Missouri

June 9, 2000.

Address correspondence and reprint requests to Merlin G. Butler, MD, PhD, Section of Medical Genetics and Molecular Medicine, Children's Mercy Hospitals and Clinics, 2401 Gillham Rd., Kansas City, MO 64108. Address e-mail to

We reviewed of a number of genetic diseases known or at risk for sedation or anesthesia complications. Some of these conditions are relatively common (e.g., Down's syndrome) whereas others are rare or present with multiple congenital anomalies that have an impact on health care delivery. We listed complications, recommended presedation evaluations, and included checklist items to assist the health care provider administering sedation and anesthesia. A better recognition and awareness of risk factors associated with specific genetic diseases should lessen the likelihood of complications during these procedures.


This article provides a brief description of potential problematic genetic disorders and associated complications that may manifest during sedation or anesthesia. Recommendations for presedation evaluation and checklist items are given that may impact on the delivery of care for these patients.


Patients with common or uncommon genetic disorders, with or without multiple congenital anomalies, present unique challenges to the health care provider responsible for administering sedation and anesthesia during surgical or technical procedures. Patients affected with heritable diseases often have special health-related needs requiring attention before successful sedation or anesthesia. It is important for health care providers, including nurses and physicians treating these patients, to recognize risk factors and potential complications before sedation or anesthesia.

A brief description of potential problematic genetic disorders and associated complications is presented that may manifest during sedation or anesthesia. Recommendations for presedation evaluation and checklist items are given that may have an impact on the delivery of care for these patients. This review is not intended as a comprehensive survey of all genetic diseases with possible complications relating to anesthesia, but it does list specific conditions with known or potential risks for complications. In addition, specific recommendations are given to provide strategies to alleviate possible problems.



The genetic diseases described in this report were chosen by five selection processes: 1) searching for potential risk factors (e.g., severe hypotonia, airway obstruction, vertebral anomalies) for sedation and/or anesthesia in the 15 most common genetic disorders from a Canadian population survey of genetic diseases reported by Baird et al.; this survey identified the most common genetic disorders in specific etiologic categories, including single gene (autosomal dominant, autosomal recessive, and X-linked), chromosomal and multifactorial; 2) by personal experience or verbal communication with health care providers from major medical centers providing care for patients with genetic conditions; 3) searching for potential risk factors for sedation and/or anesthesia in the ten most common genetic diseases referred for genetic services reported from a major medical center in the United States ; 4) reviewing the most current edition of Smith's Recognizable Patterns of Human Malformation , a principle textbook used in the clinical practice of genetics, and identifying those diseases with features (e.g., anatomic airway obstruction) that may complicate sedation/anesthesia procedures; and 5) an online computer search of the medical literature by using Medline and other computer health databases searching for reported sedation/anesthesia complications in patients with genetic diseases. One hundred sixty-three conditions were identified and summarized in tabular form in this article.




The results of this survey, including sedation and anesthesia considerations/complications for patients with selected genetic disorders, are summarized in table 1, table 1A, table 1B, table 1C, table 1D, table 1E, table 1F, table 1G, table 1H, table 1I, table 1J, table 1K, table 1L, table 1M, table 1O, which is arranged alphabetically by disease. The disorder and its etiology are listed in table 1, table 1A, table 1B, table 1C, table 1D, table 1E, table 1F, table 1G, table 1H, table 1I, table 1J, table 1K, table 1L, table 1M, table 1O. A brief description of each condition is given along with potential sedation and anesthesia complications. Recommendations for presedation evaluation are also given, and references are cited. Items that may have an impact on the delivery of care to the patient include a difficult airway as a result of upper or lower airway obstruction or defects (e.g., cleft lip/palate, small chin or mouth, macroglossia, choanal stenosis/atresia, tracheomalacia, tracheoesophageal fistula, craniofacial deformities); altered respiratory mechanisms caused by skeletal anomalies (e.g., small chest, rib, sternal, or vertebral anomalies); bronchopulmonary hypoplasia or altered respiratory drive; gastric reflux; cardiovascular disorder (arrhythmia or structural defect); neuromuscular problems (e.g., myotonia, muscular dystrophy or weakness; central nervous system defects); and liver and kidney disease. Comments are made regarding adverse effects of opioids, neuromuscular drugs and succinylcholine reported in the literature. Caution should be taken with the use of specific drugs in patients with liver disease (e.g., liver is the major site for biotransformation for most opioids) and at risk for decreased drug clearance. Adverse reactions to succinylcholine consist primarily of an extension of its pharmacological action and can cause prolonged muscle relaxation. Adverse reactions may include cardiac arrhythmias, malignant hyperthermia, hyper/hypotension, hyperkalemia, respiratory depression, muscle fasciculation and pain, joint rigidity, acute renal failure, excessive salivation, and rash. Therefore, patients with genetic conditions affecting certain organ systems (e.g., heart, liver, kidney) should be monitored more closely for these reactions. Drugs that may enhance the neuromuscular blocking action of succinylcholine should be noted, including several medications that may be prescribed for patients with genetic disorders. These may include nonpenicillin antibiotics, beta-blockers, procainamide, lithium carbonate, glucocorticoids, metoclopromide, terbutaline, and monoamine oxidase inhibitors.


This study gives a brief overview of potential sedation and anesthesia complications with recommendations for presedation evaluation that health care providers may encounter when administering anesthesia or sedation to patients with specific genetic disorders. Checklist items are given involving several major organ systems that have a direct impact on the administration of anesthesia or sedation for each genetic condition described. This review should allow the anesthesiologists to be alerted to potential risk factors and recommendations for presedation evaluation for each patient with the specific genetic condition listed. Special attention should be given to the checklist items (particularly liver and renal problems) when sedation/anesthetics are used that require normal liver function and renal clearance for optimal use and how the organ system involvement may have an impact on their drug selection and administration. Those patients with muscular dystrophies (e.g., Duchenne's), myotonic dystrophy, or central cord disease may be at risk for developing malignant hyperthermia. This listing is not intended to be a comprehensive review of all genetic diseases, but it focuses attention on conditions with known risk factors identified through personal experience/communication and a review of medical reports, textbooks, and surveys of rare and more common genetic conditions that may be encountered by the health care providers administering sedation or anesthesia.

The most prevalent concern is airway obstruction/defects and management issues followed by altered respiratory mechanisms (see table 1, table 1A, table 1B, table 1C, table 1D, table 1E, table 1F, table 1G, table 1H, table 1I, table 1J, table 1K, table 1L, table 1M, table 1O). Careful intubation and close monitoring of the airway are necessary to guard against serious complications or obstructions in several diseases as a result of anatomic problems or neurologic impairment. Other major factors encountered are vertebral and rib abnormalities, craniofacial anomalies, and/or increased hyperextensibility caused by skeletal or connective tissue disorders. Proper positioning and supportive care of the patient's head during intubation and surgical or invasive procedures should prevent most spinal nerve injuries and possible paralysis in these patients. Hypertension is also noted as a risk factor for a number of genetic disorders, caused by metabolic conditions, adverse effects of anesthesia medications. or congenital anatomical problems (e.g., cardiovascular or renal). When dealing with hypertensive patients, the standard protocol of monitoring cardiovascular, renal, and pulmonary function on a continuing basis should be closely followed. In addition, possible adverse reactions to certain medications that may cause cardiac arrhythmias, rigidity, hypertension, prolonged sedation, acute renal failure, and respiratory distress must be monitored in patients with specific genetic diseases. As indicated in table 1, table 1A, table 1B, table 1C, table 1D, table 1E, table 1F, table 1G, table 1H, table 1I, table 1J, table 1K, table 1L, table 1M, table 1O, several conditions with multiple organ system involvement may present with early death (e.g., trisomy 13 and 18).

The uncooperative patient can also be a challenge, specifically, those with mental deficiency, psychiatric diagnoses, or aberrant behavior. Special attention must be given to make the patient feel as comfortable

as possible. Special behavior assessments may be required before sedation or anesthesia administration to meet or gain the trust of the patient and family and to alleviate problems. Exaggerated anxiety may lead to further tactile defensiveness, hyperactivity, attention deficits, psychomotor disturbances, and uncooperativeness. Desensitization and allaying anxiety are important key points to remember before successful sedation or anesthesia administration in patients with special needs. This is particularly important for patients with genetic diseases with neurologic involvement [approximately 60% of the reported 10,000 genetic conditions have central or peripheral nervous system abnormalities]. In addition, hearing impairment and blindness are recognized features of several genetic diseases that raise additional problems for the health care provider.



Table 1

Sedation and Anesthesia Considerations/Complications for Patients with Selected Genetic Disorders


Brief Description

Potential Sedation and Anesthesia Complications

Recommendations for Presedation Evaluation

Checklist Items

Difficult airway

Altered respiratory mechanics

Gastric reflux

Cardio- vascular disorder

Neuro- muscular problems

Liver disease

Renal disorder

Kabuki Make-Up Syndrome: sporadic

Growth and mental deficiency, long palpebral fissures, epicanthal folds, tooth abnormalities

Structural: Cleft palate, scoliosis, cardiac and urogenital defects, joint hyperextensibility, sagittal cleft of vertebral body, pectus, diaphragmatic eventration Neuro: Hypotonia, seizures

Radiologic evaluation for vertebral defects; evaluate for upper airway obstruction or defects and cardiac function





{tabft}Neuro = neurological, CNS = central nervous system, PEEP = positive end-expiratory pressure, Misc = miscellaneous, ECG = electrocardiogram, cAMP = cyclic adenosine monophosphate, GE = gastroesophageal.

Genetic disorders pose a significant challenge to health care providers. The recognition of genetic conditions is increasing in the United States, with many patients not previously encountered requiring surgical procedures and intervention with anesthesia. This is a result of changing medical practice, growing awareness and recognition of genetic diseases, modern medical advances, and increased longevity of patients with many genetic conditions. With increased prevalence (and incidence) of genetic diseases and with better recognition comes the need for comprehensive efforts of health care providers to meet the growing special needs of each patient. Acknowledging unique anesthesia considerations is an essential part of providing adequate health care for patients with genetic diseases and can serve as a means of avoiding morbidity and mortality.


1.Baird P, Anderson T, Newcombe H, Lowry R. Genetic disorders in children and young adults: a population study. Am J Hum Genet 1988; 42: 677-93.
2. Woodward A, Alves S, Butler MG. Genetic conditions among patients receiving genetic services in middle Tennessee. So Med J 1993; 86: 42-5.
3. Jones, K. Smith's recognizable patterns of human malformation. 5th ed. Philadelphia: WB Saunders, 1997.
4. Online Mendelian Inheritance in Man, OMIM. Center for Medical Genetics, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Med (Bethesda, MD). Available at Accessed April 14, 1999.
5. Montogama E, Davis P. Smith's anesthesia for infants and children. [Not Available] 6th ed. St. Louis: Mosby-Year Book, 1996: 953-61.
6. Nargozian C. Anesthetic management. Clin Plas Surg 1991; 18: 227-30.
7. Katz J, Steward D. Anesthesia and uncommon pediatric diseases. [Not Available] 2nd ed. Philadelphia: WB Saunders, 1993: 467-8.
8. Bevan J. Congenital syndromes in pediatric anesthesia: what is important to know. Can J Anaesth 1998; 45: R3-9.
9. Sculerati N, Gottlieb M, Zimbler M, et al. Airway management in children with major craniofacial anomalies. Laryngoscope 1998; 108: 1806-12.
10. Vaughan C. Anesthetic management of children with craniofacial anomalies. CRNA 1997; 8: 123-34.
11. Kalla G, Fening E, Obiaya M. Anaesthetic management of achondroplasia. Br J Anaesth 1986; 58: 117-9.
12. Stiles C. Anesthesia for the mentally retarded patient. Ortho Clin North Am 1981; 12: 45-56.
13. Vas L, Naregal P, Karmarkar S. Maxillary hypoplasia with unsuspected choanal atresia. Ped Anaesth 1997; 7: 465-7.
14. LeBard S, Thiemann L. Antley-Bixler syndrome: a case report and discussion. Ped Anaesth 1998; 8: 89-91.
15. Shiraishi N, Nakamura T, Saito H, et al. Anesthetic management of a patient with Cowden syndrome. Masui 1995:282-5.
16. Kim Y, Shibutani T, Hirota Y, et al. Anesthetic considerations of two sisters with Beckwith-Wiedemann syndrome. Anesth Prog 1996; 43: 24-8.
17. Suan C, Ojeda R, Garcia-Perla J, Perez-Torres M. Anaesthesia and the Beckwith Wiedemann syndrome. Paediatr Anaesth 1996; 6: 231-3.
18. Schulte D, Kasperbauer J. Safety of paranasal sinus surgery in patients with cystic fibrosis. Laryngoscope 1998; 108: 1813-5.
19. Poussa M, Merikanto J, Ryoppy S, et al. The spine in diastrophic dysplasia. Spine 1991; 16: 881-7.
20. Fox H, Thomas C, Thompson A. Spinal instrumentation for Duchenne's muscular dystrophy: experience of hypotensive anaesthesia to minimize blood loss. J Paediatr Ortho 1997; 17: 750-753.
21. Brighouse D, Guard B. Anaesthesia for caesarian section in a patient with Ehlers-Danlos syndrome type IV. Br J Anaesth 1992; 69: 517-9.

22. Woolley M, Morgan S, Hays D. Heritable disorders of connective tissue surgical and anesthetic problems. J Pediatr Surg 1967; 2: 325-31.
23. Goldring S. Pediatric epilepsy surgery. Epliepsia 1987; 28: 82-102.
24. Louhhimo I, Lindahl H. Esophageal atresia, primary results of 500 consecutively treated patients. J Pediatr Surg 1983; 18: 217-29.
25. Nussbaum BL, Ohara I, Kaplan FS. Fibrodysplasia ossificans progressiva: report of a case with guidelines for pediatric dental and anesthetic management. ASDC J Dent Child 1996; 63: 448-50.
26. Casamassimo P, Mcllvaine W, Hagerman R, Shellhart W. General anesthesia and fragile X syndrome: report of a case. Anesth Prog 1985; 32: 104-6.
27. Madan R, Trikha A, Venkataraman RK, et al. Goldenhar's syndrome: an analysis of anaesthetic management. Anaesth 1990; 45: 49-52.
28. Borland L. Anesthesia for children with Jeune's syndrome (asphyxiating thoracic dystrophy). Anaesth 1987; 66: 86-8.
29. Tritapepe L, Voci P, Pinto G, et al. Anaesthesia for caesarian section in a Marfan patient with recurrent aortic dissention. Can J Anaesth 1996; 43: 1153-5.
30. Wells D, Podolakin W. Anaesthesia and Marfan's syndrome: case report. Can J Anaesth 1987; 34: 311-4.
31. Tobias J. Anaesthetic considerations in the child with Menkes' syndrome. Can J Anaesth 1992; 39: 712-5.
32. Busoni P, Fognani G. Failure of the laryngeal mask to secure the airway in a patient with Hunter's syndrome. Ped Anaesth 1999; 9: 153-5.
33. Baines D, Keneally J. Anaesthetic implications of the mucopolysaccharideoses: a fifteen year experience in a children's hospital. Anaesth Intensive Care 1983; 11: 198-202.
34. Hopkins R, Watson J, Jones J, Walker M. Two cases of Hunter's syndrome: the anaesthetic and operative difficulties in oral surgery. Br J Oral Surg 1973; 10: 286-99.
35. Moores C, Rogers JG, McKenzie M, Brown TCK. Anaesthesia for children with mucopolysaccharidoses. Anaesth Intensive Care 1996; 24: 459-63.
36. Walker R, Darowski M, Morris P, Wraith J. Anaesthesia and mucopolysaccharidoses. Anaesthesia 1994; 49: 1078-84.
37. Kuzma PJ, Calkins MD, Kline MD, et al. The anesthetic management of patients with multiple pterygium syndrome. Anesth Analg 1996; 83: 430-2.
38. Naguib M, Al-Rajeh S, Abdulatif M, Abatin W. The response of a patient with Von Recklinghausen's disease to succinylcholine and atracurium. MEJ Anesth 1988; 9: 429-34.
39. Fisher M. Anaesthetic difficulties in neurofibromatosis. Anaesthesia 1975; 30: 648-50.
40. Ransom D, Leicht C. Continuous spinal analgesia with Sufentanil for labor and delivery in a parturient with severe pulmonary stenosis. Anesth Analg 1995; 80: 418-21.
41. Bolsin S, Gilbe C. Opitz-Frias syndrome. Anaesthesia 1985; 40: 1189-93.
42. Jones S, Derrick G. Difficult intubation in an infant with Pierre Robin syndrome and concomitant tongue tie. Pediatr Anaesth 1998; 8: 510-1.
43. Silverstein K, Adams M, Fonseca R. Evaluation and management of the renal failure and dialysis patient. Oral Maxillofac Surg Clin North Am 1998; 10: 417-27.
44. Dearlove O, Dobson A, Super M. Anaesthesia and Prader-Willi syndrome. Pediatr Anaesth 1998; 8: 267-71.
45. Makenzie JW. Anaesthesia and the Prader-Willi syndrome. J Roy Soc Med 1991; 84: 239.
46. Chapin JW, Kahre J. Progeria and anesthesia. Anesth Analg 1979; 58: 424-5.
47. Macdonald I, Dearlove OR. Anaesthesia and Robinow syndrome [letter]. Anaesthesia 1995; 50: 1097.
48. Dinner M, Goldin E, Ward R, et al. Russell-Silver syndrome: anesthetic implications. Anesth Analg 1994; 78: 1197-9.
49. Vipond AJ, Caldioctt LD ,. Major vascular surgery in a patient with sickle cell disease. Anesth 1998; 53: 1204-6.
50. Peterson W, Crouch E. Anesthesia-induced rigidity, unrelated to succinylcholine, associated with Smith-Lemli-Opitz syndrome and malignant hyperthermia. Anesth Analg 1995; 80: 606-8.
51. Batra RK, Veena G, Madan R, Trikha A. Anesthesia and the Sturge-Weber syndrome. Can J Anaesth 1994; 41: 133-6.
52. Lee J, Imrie M, Taylor V. Anaesthesia and tuberous sclerosis. Br J Anaesth 1994; 73: 421-5.
53. Conway J, Posner M. Anaesthesia for caesarian section in a patient with Watson's syndrome. Can J Anaesth 1998; 41: 1113-6.
54. Carter G, Bonekat H, Milio L. Successful pregnancies in the presence of spinal muscular atrophy: two case reports. Arch Phys Med Rehabil 1994; 75: 229-31.
55. Patel J, Harrison M. Williams syndrome: masseter spasm during anesthesia. Anaesthesia 1991; 46: 115-6.

We thank Karen Henrion for expert preparation of the manuscript. We thank William Daniels, DO, pediatric anesthesiologist, for his critical reading of the manuscript and helpful suggestions.