Turner syndrome and anesthesia

Abstracts

JUSTIFICATIVA E OBJETIVOS: A síndrome de Turner é uma anormalidade genética freqüente e complexa, que afeta mulheres e está associada a uma grande variedade de alterações anatômicas e fisiológicas, em especial relacionadas com as vias aéreas e o sistema cardiovascular. Foi objetivo deste artigo fazer uma revisão das alterações anatomofisiológicas da síndrome de Turner de maior interesse para o anestesiologista, discutir o manuseio perioperatório e fazer uma revisão da literatura a respeito da conduta anestésica nesses pacientes. CONTEÚDO: A síndrome de Turner é uma doença genética caracterizada por anormalidade no número ou morfologia do cromossomo sexual. Com mais freqüência o cromossomo sexual é ausente, resultando em cariótipo 45,X e um fenótipo de disgenesia gonadal. As principais alterações anatomofisiológicas de interesse para o anestesiologista incluem pescoço curto e hipoplasias maxilar e mandibular, o que pode provocar uma via aérea difícil. O menor comprimento da traquéia, bem como sua bifurcação mais superior, pode facilitar a intubação endobrônquica e extubação traqueal acidental quando houver tração da cânula traqueal. Cardiopatias, doenças endócrinas e gastrintestinais, alterações hepáticas e renais, comprometimento osteoarticular, bem como alterações oftálmicas e auditivas, são freqüentes, devendo ser detectados durante a avaliação pré-anestésica. As técnicas de anestesia geral ou regional parecem ser seguras nesse tipo de paciente. CONCLUSÕES: A síndrome de Turner é uma anormalidade genética que apresenta importantes alterações anatomofisiológicas de interesse para o anestesiologista. O conhecimento dessas alterações permite manuseio anestésico seguro com baixa morbimortalidade perioperatória.

COMPLICAÇÕES; DOENÇAS, Genética

JUSTIFICATIVA Y OBJETIVOS: El síndrome de Turner es una anormalidad genética frecuente y compleja que afecta a las mujeres y que está asociada a una gran variedad de alteraciones anatómicas y fisiológicas en especial relacionadas con las vías aéreas y el sistema cardiovascular. Fue objeto de este artículo hacer una revisión de las alteraciones anátomo-fisiológicas del síndrome de Turner de mayor interés para el anestesiólogo, discutir el manoseo perioperatorio y hacer una revisión de la literatura respecto de la conducta anestésica en esos pacientes. CONTENIDO: El síndrome de Turner es una enfermedad genética caracterizada por una anormalidad en el número o en la morfología del cromosoma sexual. Frecuentemente el cromosoma sexual falta, resultando en cariótipo 45,X y un fenotipo de disgenesia gonadal. Las principales alteraciones anatomo-fisiológicas de interés para el anestesiólogo incluyen cuello corto, hipoplasia maxilar y mandibular lo que puede provocar una vía aérea difícil. La extensión más corta de la tráquea como su bifurcación más superior, puede facilitar la intubación endobrónquica y la extubación traqueal accidental cuando haya una tracción de la cánula traqueal. La presencia de cardiopatías, enfermedades endocrinas y gastrointestinales, alteraciones hepáticas y renales como también la extensión ósteo-articular además de las alteraciones oftálmicas y auditivas son frecuentes debiendo ser detectadas durante la evaluación preanestésica. Las técnicas de anestesia general o regional parecen ser seguras en este tipo de pacientes ³. CONCLUSIONES: El síndrome de Turner es una anormalidad genética que presenta importantes alteraciones anátomo-fisiológicas de interés para el anestesiólogo. El conocimiento de esas alteraciones permite el manejo anestésico seguro con una baja morbi-mortalidad perioperatoria.

MISCELLANEOUS

Turner syndrome and anesthesia^*

Síndrome de turner y anestesia

Marcius Vinícius M. Maranhão, TSA

Professor de Farmacologia do Instituto de Ciências Biológicas da Universidade de Pernambuco; Chefe do Serviço de Anestesiologia do Pronto-Socorro Cardiológico de Pernambuco, Universidade de Pernambuco; Co-Responsável pelo CET/SBA do Hospital da Restauração e Hospital Getúlio Vargas; Anestesiologista do NCT – Hospital da Real Beneficência Portuguesa e Hospital São Marcos

^{Correspondence to}

SUMMARY

BACKGROUND AND OBJECTIVES: Turner syndrome is a frequent and complex genetic abnormality affecting women, being associated with a wide variety of anatomical and physiological changes, especially related with the airways and cardiovascular system. The objective of this report was to review the anatomopathologic changes of this syndrome that concern the anesthesiologist the most, discuss the perioperative management and review the literature regarding the anesthetic conduct in those patients.

CONTENTS: Turner syndrome is a genetic disorder characterized by an abnormality in the number or morphology of the sex chromosome. The most frequent abnormality is the absence of a sex chromosome, resulting in the 45X karyotype and a phenotype composed of gonadal dysgenesis. The main anatomo-physiological changes pertaining the anesthesiologist include a short neck, and maxillary and mandibular hipoplasia, which might be responsible for difficult airways. The shorter length of the trachea, as well as the higher location of its bifurcation, can predispose to bronchial intubation and accidental endotracheal extubation when the tracheal cannula is under traction. The presence of cardiopathies, endocrine and gastrointestinal disorders, liver and kidney changes, as well as osteoarticular involvement, besides ophthalmologic and hearing impairments, are very frequent, and should be detected during the pre-anesthetic evaluation. General or regional anesthesia seems to be safe for those patients.

CONCLUSIONS: Turner syndrome is a genetic abnormality with important anatomo-physiological abnormalities important to the anesthesiologist. The knowledge of this disorder allows for a safer anesthetic management with low perioperative morbimortality.

Key Words: COMPLICATIONS: intubation; DISEASES, Genetic: Turner syndrome.

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: El síndrome de Turner es una anormalidad genética frecuente y compleja que afecta a las mujeres y que está asociada a una gran variedad de alteraciones anatómicas y fisiológicas en especial relacionadas con las vías aéreas y el sistema cardiovascular. Fue objeto de este artículo hacer una revisión de las alteraciones anátomo-fisiológicas del síndrome de Turner de mayor interés para el anestesiólogo, discutir el manoseo perioperatorio y hacer una revisión de la literatura respecto de la conducta anestésica en esos pacientes.

CONTENIDO: El síndrome de Turner es una enfermedad genética caracterizada por una anormalidad en el número o en la morfología del cromosoma sexual. Frecuentemente el cromosoma sexual falta, resultando en cariótipo 45,X y un fenotipo de disgenesia gonadal. Las principales alteraciones anatomo-fisiológicas de interés para el anestesiólogo incluyen cuello corto, hipoplasia maxilar y mandibular lo que puede provocar una vía aérea difícil. La extensión más corta de la tráquea como su bifurcación más superior, puede facilitar la intubación endobrónquica y la extubación traqueal accidental cuando haya una tracción de la cánula traqueal. La presencia de cardiopatías, enfermedades endocrinas y gastrointestinales, alteraciones hepáticas y renales como también la extensión ósteo-articular además de las alteraciones oftálmicas y auditivas son frecuentes debiendo ser detectadas durante la evaluación preanestésica. Las técnicas de anestesia general o regional parecen ser seguras en este tipo de pacientes ³.

CONCLUSIONES: El síndrome de Turner es una anormalidad genética que presenta importantes alteraciones anátomo-fisiológicas de interés para el anestesiólogo. El conocimiento de esas alteraciones permite el manejo anestésico seguro con una baja morbi-mortalidad perioperatoria.

INTRODUCTION

Turner syndrome (TS) was first described in 1938 by the American physician Henry Turner. It is characterized by changes in the sex chromosomes, affecting females. Most patients present the 45X karyotype, although other karyotypes might be present, indicating the presence of structural changes in the second X chromosome. The 45X karyotype is almost always secondary to a lack of paternal disjunction during meiosis, since the X chromosome is usually of maternal origin ¹.

Turner syndrome is the most common chromosomal abnormality, however it has an incidence of only 1 in 2,500 to 3,000 live females due to the high frequency of spontaneous miscarriages ^2,3. In Brazil, according to the data of the IBGE (for Brazilian Institute of Statistical Geography) there are approximately 16,000 women with this syndrome.

Turner syndrome is associated with wide anatomical and physiological changes that are important for the anesthesiologist. The objective of this report was to review those changes, discuss the perioperative management and review the literature regarding the anesthetic conduct in those patients in order to decrease perioperative morbimortality.

ANATOMOPATHOLOGICAL CHANGES IN TURNER SYNDROME

Development

A short stature is the most common characteristic of women with Turner syndrome ^1,4,5. Turner syndrome is characterized by slow intrauterine growth, normal growth during the first years of life, progressive growth deceleration later in childhood and absence of the marked pubertal growth ⁶. To minimize the short stature, women with Turner syndrome frequently use hormone-based treatments, such as oxandrozone, growth hormone and estrogen ¹. It is important to emphasize that the effects of the prolonged treatment with growth hormone may cause an increase in insulin resistance and blood pressure ³.

Head and Neck Abnormalities

Patients with Turner syndrome have a short and wide neck, webbed neck, severe limitation in neck mobility, high arched palate, prominent low-set ears and maxillary and mandibular hipoplasia ^1,3-5,7. Multiple arthrogryposis, a genetic disorder characterized by contracture of several joints is more frequent in TS patients ⁸ and may affect the temporomandibular joint, which limits mouth opening.

Cardiovascular System

Cardiac abnormalities, such as coarctation of the aorta, bicuspid aortic valve and aortic stenosis are present in 17% to 45% of the patients ^1-4,6. It should be noted that patients with coarctation of the aorta can develop severe perioperative hypertension ⁷. Hypertension, mitral valve prolapse, anomalous drainage of the pulmonary veins and cardiac conduction defects may also be present ^2,6. Hypercholesterolemia is frequent, although the risk of coronary artery disease in patients with Turner syndrome is unknown ². There are more than 80 cases reported in the literature of aortic dissection in TS patients. Coarctation of the aorta, bicuspid aortic valve, hypertension or a combination of those factors represent the risk for aortic dissection ².

Respiratory System

The trachea of patients with TS is smaller than in the general population. The tracheal bifurcation can be at the level of the sternoclavicular joint instead of at the level of the second thoracic vertebra ¹⁴.

Nervous System

Most patients with Turner syndrome have a normal IQ. Approximately 10% might present important mental retardation. Depression and seizures may also be present. Anxiety during adolescence is a common feature ^2,3-7.

Gastrointestinal and Hepatic Systems

Gastroesophageal reflux is common, as well as inflammatory bowel disease (Crohn's disease, ulcerative colitis, and chronic diarrhea of unknown etiology). The incidence of celiac disease is increased in TS patients. The incidence of gall bladder disease might be elevated without association with diabetes mellitus or obesity. Hepatic steatosis, reduction in hepatic metabolism, bleeding disorders and elevation in liver enzymes may be present ^2,3.

Endocrine and Reproductive Systems

Hypothyroidism affects 15% to 30% of patients with Turner syndrome, being more frequent in the third decade of life although 5% to 10% of the cases occur before adolescence. Patients might present autoimmune diseases, such as Hashimoto's thyroiditis. Patients with TS can also present increased insulin resistance resulting in diabetes mellitus ^1,3-6. Gonadal dysgenesis with absence of secondary sexual characteristics is a typical sign of TS. Approximately 90% of the patients need hormone replacement therapy to begin puberty and complete their growth. The effects of hormonal replacement therapy on liver function and bone density are unknown, although there are reports of liver dysfunction with elevation of hepatic enzymes. The breasts are usually underdeveloped. The vagina and uterus may be absent, hypodeveloped or ill-developed ^1,2-4. Primary amenorrhea and sterility are characteristic in those patients ⁴. Obesity is a frequent feature ².

Kidneys

Kidney changes include horseshoe kidneys and duplication of the renal collecting system, which might affect 40% of the patients. However, most of those structural changes do not hinder kidney function. Hydronephrosis secondary to obstruction of the duplicated collecting system may be present ^1-4.

Eyes and Ears

Epicanthic folders, strabismus, palpebral ptosis, cataract and nystagmus are not uncommon ^1,2,5,6. Recurring ear infections and deafness might be present in those patients ^1,2,5,6.

Osteoarticular and Muscular Systems

Common abnormalities in TS include cubitus valgus, dislocation of the patella, chronic knee pain, congenital dislocation of the hips, scoliosis, osteoporosis, disseminated idiopathic skeletal hyperostosis, shortened 4^th metacarpus or metatarsus, decrease in carpal angle (Madlung's deformity), lowered medial femoral condyle (Kosonicz sign), temporary congenital lymphedema of feet and hands and spina bifida.

ANESTHETIC CONDUCT

The anesthesiologist should be aware of the most frequent anatomo-physiological changes in Turner syndrome and their repercussions in the anesthetic-surgical procedure.

Although most patients with Turner syndrome have normal intelligence, a small percentage might present mental retardation which, if associated with hearing deficits, can limit physician-patient relationship. In those cases, it is important that parents or legal guardians be present during the pre-anesthetic evaluation and discuss with the anesthesiologist the proposed anesthetic technique. An informed consent should be obtained from the patient, parents, or legal guardians ³.

Maxillary and mandibular hipoplasia, associated with a short and wide neck, may impose difficulties to tracheal intubation. It is important to remind that the contracture of the temporomandibular joint in patients with multiple congenital arthrogryposis might be responsible for difficult intubation in TS patients ⁸. Therefore, it can be considered that those patients have difficult airways, which should be carefully evaluated. Laryngeal mask, fiberoptic endoscope and material for the surgical approach of the airways should be readily available during tracheal intubation maneuvers. Tracheal intubation should be done preferentially on the awake patient, under topical anesthesia of the oropharynx and laryngeal or transtracheal nerve block, with the patient mildly sedated with low doses of benzodiazepines and opioids. The trachea in those patients is shorter and the tracheal bifurcation is higher favoring endobronchial intubation and accidental extubation whenever the tube is under traction ^3-4. One should suspect of endobronchial intubation in the presence of a sudden increase in airway pressure, absence of breath sounds on auscultation and decreased peripheral oxygen saturation ⁹.

The increased incidence of cardiopathies requires a preoperative echocardiogram and in the presence of possible ischemic cardiopathy a stress test should be done to rule out the presence of changes in the cardiovascular system. Strict blood pressure control is mandatory in patients with coarctation of the aorta.

The presence of hypothyroidism could slow gastric emptying. Hypothermia and hypotension caused by the anesthetic agents may delay recovery from anesthesia. It is important to establish a preoperative euthyroid condition. In those patients and in patients with gastroesophageal reflux, pre-anesthetic medication should include drugs that increase gastric pH (sodium citrate, H₂ antagonists, inhibitors of gastric proton pump) and gastro kinetic agents (metoclopramide). One should keep in mind that those patients have an increased incidence of diabetes mellitus requiring adequate intraoperative control of glucose levels, avoiding severe hyperglycemia and, especially, hypoglycemia ³.

In cases with liver and kidney diseases, one should be cautious when using drugs metabolized by the liver and excreted by the kidneys ³. The clotting system should be evaluated preoperativelly and, if necessary, vitamin K should be administered ³.

Preoperative exams should be done according to the anatomo-physiological changes of the patients and the type of procedure.

Those patients might be taking growth hormone, estrogens, thyroid hormone, insulin, oral hypoglycemic agents and drugs for the treatment of hypertension, and the anesthesiologist should be aware of the pharmacological profile of these drugs.

In the rare reports of anesthetic procedures in patients with Turner syndrome, anesthetics and adjuvant drugs like atropine, thiopental, succinylcholine, nitrous oxide, meperidine, prometazine, midazolam, fentanyl, propofol, cisatracurium and isoflurane have been safely used ^3-4. In patients with coarctation of the aorta, one should avoid using ketamine and pancuronium due to the risk of severe hypertension ¹.

Regional blocks (neuro axis and peripheral blocks) are excellent choices for patients with TS. However, due to their short stature, the doses of the local anesthetics should be individualized. It should be mentioned that the incidence of scoliosis is increased in those patients, which might hinder subarachnoid or epidural punctures.

Turner syndrome is a genetic disorder characterized by an abnormality in the number or morphology of the sex chromosome. In the most common presentation the sex chromosome is absent, resulting on a 45X karyotype and a phenotype of gonadal dysgenesis ³. The main anatomo-pathological changes concerning the anesthesiologist include a short neck, and maxillary and mandibular hipoplasia, which might be responsible for a difficult airway. The shorter trachea, as well as its higher bifurcation, may predispose to endobronchial intubation and accidental endotracheal extubation when the tracheal tube is under traction. The presence of cardiopathies, endocrine and gastrointestinal disorders, liver and kidney abnormalities, as well as osteoarticular changes, besides ophthalmologic and hearing deficits, are frequent and should be detected during the pre-anesthetic evaluation. Techniques of general or regional blocks seem safe in those patients ³.

REFERENCES

Submitted em 6 de janeiro de 2007

Accepted para publicação em 9 de outubro de 2007

• 01. Weinberg GL Genetics in Anesthesiology: Syndromes and Science. Boston, Butterworth Heinemann, 1996;206-208.
• 02. Sybert VP, McCauley E Medical progress: Turner's syndrome. N Engl J Med, 2004;351;1227-1233.
• 03. Mashour GA, Surder N, Acquadro MA Anesthetic management of Turner syndrome: a systematic approach. J Clin Anesth, 2005;17:128-130.
• 04. Divekar VM, Kothari MD, Kamdar BM Anaesthesia in Turner's syndrome. Can Anaesth Soc J, 1983;30:417-418.
• 05. Silva EO, Duarte AR Genética Médica: Uma Visão Panorâmica, em: Alves JGB, Ferreira OS, Maggi RS Pediatria, 3Ş Ed, Rio de Janeiro, Guanabara Koogan, 2004;180.
• 06. Llerena Jr JC Anomalias dos Cromossomas Sexuais, em: Garakushansky G Doenças Genéticas em Pediatria. Rio de Janeiro, Guanabara Koogan, 2001;133-136.
• 07. France NK Ophthalmological Disease, em: Katz J, Steward DJ Anesthesia and Uncommon Pediatric Diseases. 2^nd Ed, Philadelphia, WB Saunders, 1993;367.
• 08. Martin S, Tobias JD Perioperative care of the child with arthrogryposis. Paediatr Anaesth, 2006;16:31-37.
• 09. Liu WC, Hwang CB, Cheng RK et al. Unexpected left endobronchial intubation in case of Turner's syndrome. Acta Anaesthesiol Scand, 1997,35:253-256.

*

Received from Disciplina de Farmacologia do Instituto de Ciências Biológicas da Universidade de Pernambuco, Recife, PE

Publication Dates

• Publication in this collection
  17 Jan 2008
• Date of issue
  Feb 2008

History

• Received
  06 Jan 2007
• Accepted
  09 Oct 2007