Esotropia

Abstract

Marfan syndrome can reduce life expectancy and quality of life because of cardiac, orthopedic, ocular, and other system impairments. This article describes the syndrome from infancy through adolescence and our role in its identification and management.

In 1986, Flo Hyman, an Olympic silver medalist in volleyball, died suddenly during a championship match. In 1996, Jonathan Larson, a Broadway composer, died following his last trip to the emergency department where clinicians improperly diagnosed gastroenteritis. Both of these people died from an aortic rupture secondary to undiagnosed Marfan syndrome, a somewhat rare connective tissue disorder in which cardiac and other complications can cause sudden death (especially from physical exertion) or greatly impair quality of life.1

With the increasing emphasis on physical fitness and sports participation, ensuring that all children can safely engage in vigorous activity is crucial. Timely diagnosis and appropriate interdisciplinary management of Marfan syndrome are vital in preventing early deaths, unnecessary disabilities, and poor adjustment to this chronic condition.

Identifying the Disorder

Marfan syndrome, a heritable connective tissue disorder, affects between 1 in 5,000 to 1 in 10,000 Americans.2,3 It transmits through an autosomal dominant gene, but it may also occur spontaneously through a genetic mutation. It affects all races and both genders with equal frequency.1 When the syndrome occurs as a genetic mutation, patients sometimes may not receive a diagnosis until later in life or after an early, sudden death.

Cardiac complications from undiagnosed Marfan syndrome can reduce life expectancy, making it a leading cause of sudden death in young athletes.4 Major impairments in other systems, especially the skeletal and ocular systems, also occur. Patients may experience psychosocial issues relating to appearance (tall stature, long arms, pectus deformities, scoliosis, and flat feet), adaptation to a chronic condition, lifestyle restrictions, and future reproductive choices.

Children who inherit Marfan syndrome receive a dominant gene for the disorder from one parent and have a 50-50 chance of transmitting the disorder to their child. Because Marfan syndrome is transmitted as a dominant mode of inheritance, it doesn't skip generations. However, a wide spectrum of clinical expression exists among family members.5

About 25% of affected individuals acquire the disorder through a genetic mutation, and they may have more severe manifestations in multiple organ systems than those who acquire the syndrome through mendelian inheritance.5,6 Children who acquire Marfan syndrome through a genetic mutation can later transmit the gene to their children.

In the early 1990s, researchers isolated a gene (FBN-1) on the long arm of chromosome 15. This gene revealed a defect in the protein fibrillin, which is a major component of microfibrils, found in the body's connective tissue.2 The most serious manifestations of Marfan syndrome are defects of the connective tissue in the cardiovascular system, especially in the aorta. Cardiovascular manifestations may lead to aortic insufficiency, aortic aneurysm, or dissection of the aortic root. Abnormal connective tissue in the spine may cause curvatures. Abnormal connective tissue in the eye may affect the position of the lens and vision. Other manifestations of weak connective tissue are hernias, striae, and the tendency to have pneumothoraces.5

Diagnosing the Disorder

Marfan syndrome can present at any time and has a variety of signs and symptoms. Management options are available for its complications, so early diagnosis is valuable. Early detection has tremendously increased the average life span. Early detection and medical and surgical management have increased the average life span by more than 25% from 48 years in 1972 to 72 years in 1993.7

Clinical diagnosis of Marfan syndrome should involve variety of specialists including cardiologists, geneticists, and orthopedists using well-delineated major and minor criteria. Diagnostic criteria involve stringent requirements for physical findings in the patient and for diagnosing it in relatives (see Table 1, "Physical Criteria for Diagnosis").8 Despite much work in the area of molecular diagnosis, the great number of mutations prevent the creation of a reliable test with the sensitivity and specificity to identify the condition solely on a molecular basis.9

The keys to accurate diagnosis of Marfan syndrome are still family history, meticulous physical examination, awareness of the criteria for diagnosis, and a high level of suspicion to ensure appropriate referrals to specialists.10,11 If a patient receives a diagnosis early in childhood, the primary care clinician has the unique opportunity to follow the patient over time, be alert for variations that require further evaluation, and ensure appropriate follow-up with specialists.

How the Disorder Presents from Infancy to Adulthood

Infancy

Because the presentation of Marfan syndrome in infancy is often very distinctive, some researchers consider infantile Marfan syndrome a distinct clinical entity.12 Early diagnosis is important for appropriate and perhaps lifesaving management. When Marfan syndrome presents in infancy, as opposed to later childhood, serious cardiac pathology is more likely.13

If a positive family history exists, examine a newborn for clinical features of Marfan syndrome and obtain an electrocardiogram and echocardiogram.13 If a family history doesn't exist, be alert for any physical variations during the newborn assessment (see Table 2, "Possible Physical Findings in Infants").6,12-14

Marfan syndrome-related cardiac abnormalities that most commonly occur in infancy include mitral valve prolapse (MVP) and regurgitation.15 You may discover an MVP as a midsystolic click and hear a systolic murmur. MVP and regurgitation occasionally progress to produce symptoms such as shortness of breath and fatigue.15 An echocardiogram provides a definitive diagnosis.6 Rarely, pulmonary symptoms are the first indication of Marfan syndrome in infancy. In one case of infantile Marfan syndrome with the initial presentation of respiratory distress, clinicians eventually attributed the condition to a diaphragmatic hernia. This child also manifested cardiac symptoms of mitral and tricuspid valve prolapse and aortic root effacement.16

Ocular findings in the newborn may include dislocated lenses, megalocornea, and iridodonesis, but not all ophthalmologic abnormalities present during the newborn period.

Childhood

Although it's possible to diagnose Marfan syndrome in infancy, it often takes years for the full phenotype to develop.12 Performing regular, thorough examinations, especially of the cardiovascular, ocular, and musculoskeletal systems, is imperative in all children (ages 1 to 12). In a young child, the most common features of the disorder are abnormalities in the skeletal system (see Table 3, "Possible Physical Findings in Children" and Figures, "Long Fingers and Loose Joints").11,12,17

An eye specialist should always evaluate a child suspected of having Marfan syndrome. Slit lamp examination is necessary to document dislocated lenses. Esotropia, exophoria, and myopia are more frequent in people with Marfan syndrome than in the general population. A patient may avoid amblyopia, which sometimes doesn't present until the preschool years, with early diagnosis and management.18

Adolescence

Because many of the features associated with Marfan syndrome progress through a person's life span, adolescence (ages 13 to 19) presents another opportunity for diagnosis. The body habitus that Dr. Marfan initially described often prompts a clinician to look closely at tall, lanky adolescents.8,12,17 In adolescent patients, follow up on any new cardiac findings or symptoms, including murmurs, arrhythmias, shortness of breath, and chest pain with exertion or fatigue. Base referrals on any other positive presentations or findings (see Table 1, "Physical Criteria for Diagnosis" and Figure, "Pectus Deformity").8

Because Marian syndrome may present at any time across a person's life span, obtaining an updated family history at each well-child visit is critical. A family member with a new diagnosis of Marfan syndrome or the occurrence of a sudden death should alert the clinician to look more carefully at adolescents in the family for possible signs of the disorder.

Managing Your Patient's Care

After a patient receives a Marfan syndrome diagnosis, our role is critical in its ongoing management. Different management issues occur during each stage of life for the child and family. We can help ensure coordination of all aspects of care.

Infancy

Infants with Marfan syndrome often have severe complications, and parents must face caring for an infant who may have serious health problems. Because parents require a tremendous degree of emotional support throughout this time, help the family maneuver through the maze of specialists that a newly diagnosed infant will need.

Parents often have feelings of extreme guilt from the possibility of having passed on the disorder. A geneticist should see the family to answer their questions and arrange for testing of other family members. Parents need to learn about their genetic risks of passing on this disorder to future children.5

Dealing with extended family members presents another difficult issue. Grandparents may blame the "other side" of the family for the appearance of the disorder.5 Siblings may worry that they, too, have the disorder. After normal cardiac and genetic evaluations, siblings may also feel guilty that they escaped the condition. Discussions among parents, grandparents, and siblings and a knowledgeable counselor can help. Support groups and literature from the National Marfan Foundation (http://www.marfan.org or 1-800-8-MARFAN) can help families in the early stages of adjustment.

Seriously affected infants with MVP and regurgitation may require management for heart failure with digoxin, diuretics, or other drugs. Sometimes valve replacement is necessary.15 Parents need education about the larger issues of the syndrome and the daily issues of drug administration and possible surgery.

Developmental assessment can reassure parents during their child's early years. Although their child may have important medical needs, parents can expect to observe normal language and cognitive development. Joint laxity may mildly delay motor milestones, but the child will achieve them. Encourage parents to treat their child as normally as possible with regard to discipline and behavioral expectations. Affected children require the same preventive care, immunizations, and anticipatory guidance as all other infants.

Childhood

Management issues during childhood are the same as during infancy. These include routine primary care services, parental and family support, and the arrangement of appropriate follow-up with specialists. At each routine well-child visit, children with Marfan syndrome need a thorough evaluation of their affected systems. Skeletal examinations include measurement of linear growth, condition of the spine, and evaluation of joints for laxity, especially flat feet and the need for orthotics. Pectus conditions occasionally interfere with both cardiac and respiratory function and may need surgical intervention.19

Children with the syndrome need a yearly cardiac evaluation that includes an echocardiogram to assess the condition of the aorta. According to one estimate, severe aortic insufficiency, a ruptured aortic aneurysm, or aortic dissection account for 90% of deaths in people with Marfan syndrome.20

Later childhood years (ages 5 to 13) may bring increasing cardiac risk from an enlarging aortic root, which continues to enlarge into adolescence and adulthood. Both parents and children need to be aware of the types of activities that increase both stroke volume and cardiac output and are therefore potentially damaging. Likely triggers are strenuous activities with sudden bursts of exertion, such as weight lifting and contact sports (soccer, field hockey, football, wrestling, and basketball).1 Children should also learn to recognize cardiac symptoms, such as chest pain and syncope.21 Educate the child and the parents about appropriate, nonstrenuous forms of activity, such as walking, swimming, golf, and noncompetitive biking.22

To help delay or prevent widening of the aorta, patients, especially those in late childhood, often take betaadrenergic blockers, such as propranolol and atenolol. These drugs decrease the contractility of the heart, slow the heart rate, and reduce blood pressure." Look for adverse effects, such as fatigue in the first few months, sleep disturbance, and night terrors.19

If a child has valve function abnormalities, subacute bacterial endocarditis prophylaxis is necessary for all invasive medical and dental procedures. Before such procedures, children should take amoxicillin, or in penicillin-allergic people, clindamycin, cephalexin, or azithromycin.24

Children should also receive annual vision examinations by an ophthalmologist. Detached retinas and cataracts sometimes occur as a result of myopia and dislocated lenses. Review the symptoms of retinal detachment with children and parents:22 loss of vision, secondary strabismus, and nystagmus or leukokoria.25

Much research exists about the incidence of learning disorders and attention deficit hyperactivity disorder (ADHD) in children with Marfan syndrome. One study indicates that 50% of children with Marfan syndrome have at least one neuropsychological deficit in attention or learning.21 Other research indicates that school-aged children might have a higher incidence of learning difficulties, especially in the area of sustained visual attention, which is unrelated to the visual acuity problems common in Marfan syndrome.27 If learning and attention problems develop, help the family get appropriate psychoeducational evaluations and services. A child with the syndrome who also has ADHD shouldn't receive stimulant drugs because of potential increased stress on the heart from elevated blood pressure and increased heart rate. For this comorbid disorder, the patient needs alternative management approaches, such as cognitive and behavioral therapy, educational modifications, and individual, family, and group counseling.

Educate school personnel about the disorder so they can address the many physical, medical, and social issues that will arise during the school years. Physical education teachers and coaches must be aware of an affected child's appropriate activities and expectations.28 School social workers should support the child and educate classmates about the disorder.

Adolescence

Adolescents with Marfan syndrome may face myriad adjustment issues such as an uncertain future, disrupted body image, social and interpersonal difficulties, and limited job opportunities.3 Added to the normal teenage concerns about their appearance, teens with Marfan syndrome also worry about their height and difficulty finding clothes, the presence of chest deformities, and the possible need to wear thick, corrective eye glasses. The need for daily beta-blockers and the restriction of some activities may affect an adolescent's self-esteem and confidence. They may be angry, rebellious, shy, or withdrawn. Support groups and coping skills training often help teenagers.19

Managing adolescents with Marfan syndrome is similar to managing children with the condition. Obtain a bone age study to determine where the adolescent is in puberty and expected further growth. Annual cardiology visits with echocardiograms are essential because problems with the aorta may begin to develop during the adolescent years. Cardiologists generally recommend surgery to replace an enlarged aorta when it reaches 5 cm to 5.5 cm.15 Treatment with beta-blockers is very common during adolescence.

About one-third of adolescents with Marfan syndrome who have scoliosis will require active treatment with bracing or surgery.11 Review appropriate and safe physical activities with patients and stress the importance of nonstrenuous, noncontact activities. Adolescents need particular counseling about weight lifting, climbing steep inclines, moving furniture, and other forms of activity that increase the stress on the aorta.30

Ophthalmology follow-up is important as well as periodically reviewing the signs of retinal detachment with patients and parents. If a patient's ocular problems are extensive with minimized vision, an adolescent needs a referral to a program for the visually impaired.

The defect in connective tissue of the lung makes individuals with Marfan syndrome more susceptible to emphysema than unaffected individuals. This decrease in elasticity doesn't often cause problems until adulthood, but give an emphatic message about the importance of not smoking. Teens with the disorder are many times more likely to experience a pneumothorax than adolescents in the general population.2 Adolescents and even younger children need to know the signs of pneumothorax, which include shortness of breath and abrupt onset of chest pain.25 Activities such as scuba diving and flying in unpressurized aircraft increase the risk of injury to the lungs due to pressure changes, so people with Marfan syndrome should avoid them.22

Review reproductive health issues with adolescent patients. They should know about their 50% chance of passing on Marfan syndrome. Birth control is critical because the stress of pregnancy poses serious physical risks, especially to the cardiovascular system. An obstetrician specializing in high-risk pregnancies and a cardiologist should carefully follow young, pregnant women because of these additional stresses.

REFERENCES

1. Manusov EG, Martucci E: The Marfansyndrome: An undiagnosed killer Arch Fam Med 1994; 3(9):822-26

2. Delong N: Marfan sayndrome. NurseWeek, (California Statewide Edition) 1995;8:8-9.

3. Van Tongerloo A, De Paepe A: Psychosocial adaptation in adolescents and

young adults with Marfan syndrome: an exploratory study. J Med Genet 1998;35(5):405-09.

4. Vaska PL: Sudden cardiac death in young athletes: A review for nurses. AACN Clin Issues Crit Care Nuts 1992;3(1):243-54.

5. Pyeritz R, Gasner C: The Marfan syndrome, 4th edition. New York, N.Y.: National Marfan Foundation, 1994.

6. Fourie D, Colyn E, Van der Vyver J, et al.: Picture of the month-infantile Marfan syndrome. Am J Dis Child 1993;147(6):313-14.

7. Silverman D, Burton K, Gray J, et al.: Life expectancy in the Marfan syndrome. Am J Cardiol 1995;75(l):157-60.

8. De Paepe A, Devereaux R, Dietz H. et al.: Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet 1996;62(4):417-26.

9. Deitz H: Marfan syndrome. In: GeneReviews at GeneTest.

www.geneclinics.org/> [ 19 August 2002.1

10. Van Karnebeek C, Naeff M, Mulder, B, et al.: Natural history of cardiovascular manifestations in Marfan syndrome. Arch Dis Child 2001;84(2):129-37.

11. Professional Advisory Board: Orthopedic concerns. New York, N.Y.: National Marfan Foundation, 1998;1-7.

12. Lipscomb K, Clayton-Smith J, Harris R: Evolving phenotype of Marfan syndrome. Arch Dis Child 1997;76(l):41-46.

13. Morse R, Rockenmacher S, Pyeritz R: Diagnosis and management of infantile Marfan syndrome. Pediatrics 1990;86(6):888-95.

14. Sponseller P, Tomek 1, Pyertitz RE: Developmental dysplasia of the hip in Marfan syndrome. I Pediatr Orthop 1997;6:255-59.

15. Gillinov A, Zehr K, Redmond J, et al.: Cardiac operations in children with Marfan's syndrome: Indications and results. Ann Thorac Surg 1997;64 (10):1140-45.

16. Calaman S, Jacobs A, Crooke G, et al.: Infantile Marfan syndrome-a 5 week old with unusual pulmonary manifestations. Chest 2000;118(4 suppl):297S298S.

17. Moodie DS: Diagnosing Marfan syndrome is still based on clinical characteristics. Cleve Clin J Med 1998;65(4):179-81.

18. Izquierdo NJ, Traboulsi E, Enger C, et al.: Strabismus in the Marfan syndrome. Am J Ophthalmol 1994; 117(5):632-35.

19. Child A: Marian syndrome-Current medical and genetic knowledge: How to treat and when. J Card Surg 1997;12(2 suppl):131-36.

20. Del Rosario JD: Sudden cardiac death in young athletes: How to identify patients at risk. Consultant 1996;36(10):2280-84.

21. Committee on Genetics, American Academy of Pediatrics: Health supervision for children with Marfan syndrome. Pediatrics 1996;98(5):978-82.

22. Professional Advisory Board: Physical education and activity guidelines. New York, N.Y.: National Marfan Foundation, 1998.

23. Shares J, Berger L, Murphy E, et al.: Progression of aortic root dilatation and the benefit of long-term beta adrenergic blockade in Marfan's syndrome. N Engl J Med 1994;330:1335-41.

24. American Academy of Pediatrics: Prevention of bacterial endocarditis. In: Redbook: Report on the committee on infectious diseases. Elk Grove Village, Ill.: American Academy of Pediatrics, 2000;737-39.

25. Behrman RE, Kleigman, RM, Jenson, HB: Nelson textbook of pediatrics, 16th edition. Philadelphia, Pa.: W.B. Saunders Co., 2000;1331-928.

26. Hofman KJ, Bernhardt BA, Pyeritz RE: Marfan syndrome: Neuropsychological aspects. Am J Med Genet 1988;31(10):331-38.

27. Lannon E, DePaepe A, Leroy B, et al.: Neuropsychological aspects of Marfan syndrome. Chin Genet 1996;49(2):65-69.

28. Braverman A: Exercise and the Marfan syndrome. Med Sci Sports Exerc 1998;30(10 suppl):5387-5395.

29. Grey M, Boland E, Davidson, M, et al.: Coping skills training for youths with diabetes mellitus on intensive therapy. Appl Nurs Res 1999;12(2):3-12.

30. Baumgartner F, Omari B, Robertson J: Weight lifting, Marfan syndrome and acute aortic dissection. Ann Thorac Surg 1997;64(6):1871-72.

Patricia Ryan-Krause

RN, CPNP, MS, MSN

ABOUT THE AUTHOR

Patricia Ryan-Krause is assistant professor, Yale University School of Nursing, New Haven, Conn., and a pediatric NP, Children's Medical Group, Hamden, Conn.

Copyright Springhouse Corporation Oct 2002
Provided by ProQuest Information and Learning Company. All rights Reserved