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Lentiginosis associated with a left atrial myxoma
II
IIIII
II Illl
Lentiginosis associated with a left atrial myxoma Lata3~ Len Peterson, M.D., and W. Scott Serrill, M.D.
Portland and Albany, OR A 14-year-old white male patient with lentiginosis was in congestive heart failure. He was noted to be redheaded, and the lentigines were especially concentrated on the face, including the lips. A two-dimensional echocardiogram revealed an orange-sized mobile mass in the left atrium. Cardiac surgery for removal of the left atrial myxoma was successful, and a complete recovery was made. This is the second report of lentiginosis associated with'a left atrial myxoma and the first in which the immediate family did not have similar pigmentary changes. Lentiginosis and associated cardiac manifestations are briefly reviewed. (J AM ACAD DERMATOL10: 337-340, 1984.)
Cardiocutaneous syndromes were first noted by Lamy et al 1 in 1957, when they reported an association of abnormal pigmentation, congenital heart disease, and deafness in reviewing 1,188 cases of congenital heart disease in children. Forney et al 2 in 1966 reported a similar syndrome that also included multiple osseous defects. Two years later Walther 3 coined the term "cardioeutaneous syndrome," which included lentiginosis profusa with numerous cardiac abnormalities. Finally, in 1969, Gorlin et al a proposed the term "leopard syndrome" for a complex of congenital malformations including lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis and other cardiac abnormalities, abnormal genitalia, retardation of growth, and deafness. The association of lentiginosis and left atrial myxoma was made by Rees et al 5 in 1973 in an 18-year-old redheaded male patient whose initial presentation was loss of consciousness and left From the Department of Dermatology, The Oregon Health Sciences University, Portland. Reprint requests to: Dr. Larry Len Peterson, The Oregon Health Sciences University, Department of Dermatology, 3181 S.W. Sam Jackson Park Rd., Portland, OR 97201.
hemiparesis. He had previously been in good health with normal development. His mother and maternal uncle shared a similar pattern of lentigines with him. This is the second report of lentiginosis and left atrial myxoma and the first in which no positive family history for lentiginosis was obtainable. CASE REPORT The patient was a 14-year-old white boy with an unremarkable past history. Specifically, the patient's growth and his mental and sexual development appeared normal. He stated that his "freckles" had been present as long as he could remember and were present all year around. The time of admission to the hospital was February. He had been well until 4 weeks prior to admission, when he experienced pounding of the chest and dyspnea after running half of a lap in the gymnasium. Two weeks prior to admission he had acquired influenza-like symptoms, including malaise, fatigue, sore throat, a mildly productive cough, and a temperature elevated to 390 C. Later, myalgias, chest pain, and vomiting after meals ensued. He was seen by his family practitioner, and a hematocrit of 31% was noted. Iron supplementation was initiated, and a referral to a dermatologist for the numerous pigmented spots on his face was made. The dermatologist made the possible 337
338
Peterson and Serrill
Journal of the American Academy of Dermatology
Fig. 2. Two-dimensional echocardiogram demonstrating prolapse of left atrial myxoma (M) through the mitral valve (my) into the left ventricle (Iv). rv: Right ventricle; ra: right atrium; la: left atrium.
Fig. 1. Face showing numerous lentigines. association between the patient's lentigines and a cardiac abnormality after a murmur was auscultated. The patient was admitted to the university hospital. Physical examination revealed an ill-appearing youth with congestive heart failure. Pulse was 104 beats/min, respiratory rate 18/min, and blood pressure 110/64 mm Hg, and the patient was afebrile. Red hair, fair skin, and abundant lentigines were present on the face and lips (Fig. 1), upper back, chest, and arms. The lesions were brown to very brown. The remainder of the physical examination was noteworthy for a decrease in resonance on percussion and a decrease in breath sounds on auscultation in both bases. A hyperdynamic precordium was visible, with the point of maximal impulse at the sixth intercostal space, 11 cm lateral to the left sternal border. Cardiac examination revealed a grade 3/6 holosystolic murmur, +2 pitting edema to the knees, and jugular venous distension. The liver was tender and was determined to be 6 cm below the right costal margin. The remainder of the physical examinatibn was normal. The patient was not hyperteloric by facial measurement, and there was no apparent hearing loss, although audiometric testing was not done. No hypospadias was noted.
An electrocardiogram showed left atrial enlargement and sinus tachycardia. The chest x-ray film was consistent with congestive heart failure with bilateral pulmonary effusions and cardiomegaly. Laboratory data included normal serum chemistry except the following: blood urea nitrogen, 35 mg/dl; total bilirubin, 3.9 mg/dl; direct bilimbin, 2.1 mg/dl; alkaline phosphatase, 234 [U/liter; lactate dehydrogenase, 538%; and serum glutamic-oxaloacetic transaminase, 1,128 U/ml. Other abnormal values were as follows: prothrombin time, 25.4; partial thromboplastin time, 66.8; white blood cell count, 11,800; hematocrit, 37.6% with microcytic indices; polymorphonuclear neutrophils, 79; lymphocytes, 14; bands, 10; monocytes, 3; erythrocyte sedimentation rate, 1; platelets, 377,000; iron, 15 p.g/dl; iron-binding capacity, 307 ~g/dl; fibrinogen, 88 mg/dl; urinalysis with 1 + bilirubin and 30 mg/dl protein; elevated antistreptolysin O (ASO), 1:480; negative antinuclear antibody; and negative blood cultures. A two-dimensional echocardiogram revealed an orange-sized tumor located in the left atrium and freely falling into the left ventricle (Fig. 2). The patient underwent open-heart surgery in which an atrial myxoma was successfully removed, and a mitral valve annuloplasty was subsequently performed. The patient made a successful, uneventful recovery. Multiple skin biopsies examined postoperatively were consistent with lentiginosis (Fig. 3). The patient's mother was examined for any manifestations of the leopard syndrome, and none were apparent. The patient was an only child. When he was born, his mother was 35 years old and his father was 40 years
Volume 10 Number 2, Part 2 February, 1984
Lentiginosis associated with atrial myxoma
339
Fig. 3. Skin biopsy of lentigo, showing epidermal hyperplasia with thin, elongated rete ridges and hyperpigmentation of basal layer. (Hematoxylin-eosin stain; original magnification, • old. The father died of undiagnosed "heart trouble" 3 years after our patient was born. No autopsy was performed. DISCUSSION
The association between lentiginosis and cardiac abnormalities has been well established2 -14 These abnormalities are listed in Table I. This is only the second report involving an atrial myxoma. Our case is strikingly similar to the first case reported. Similarities include (1) redheadedness, (2) fair skin, (3) diagnosis of myxoma in teenage years, (4) normal growth and development, and (5) heavy facial involvement of lentigines. Conversely, no positive family history of lentigines was obtainable in this patient. This is puzzling because the mode of inheritance of the leopard syndrome has been reported to be autosomal dominant with variable expressivity. 1'~ Whether this syndrome was present in our patient is uncertain. His case may represent a form of spontaneous mutation, since both parents were relatively old at the time of his birth. Other alternative explanations include a failure to diagnose the syndrome in the parents because of mild expression (the father's
Table I. Cardiac abnormalities associated with lentiginosis 1. 2. 3. 4. 5. 6. 7. 8.
Axis deviations G Unilateral or bilateral hypertrophy 7"~ Prolonged PR interval s Left anterior hemiblock 1~ Bundle-branch block 1~ Complete heart block t2 Valvular disease r'la Endomyocardial fibroelastosis and obstructive cardiomyopathy~4 9. Left atrial myxorna ~
"heart condition" may have been the only sign), nonpaternity, a nongenetic disorder (phenocopy), and an association with a different genetic disorder (genocopy). It is likely that with an elevated ASO titer and elevated temperature, the patient probably had a concurrent streptococcal infection exacerbating his congestive heart failure. Liver congestion would be one way of explaining his abnormal liver functions. Why is there an association of lentigines and cardiac abnormalities? Selmanowitz et al ~ have suggested a possibie mutation in the embryonic
340
Peterson and Serrill
neural crest that c o u l d account for melanocytic ~ilterations and cardiac abnormalities. Alternatively, Polani and M o y n a h a n s h a v e proposed that the profuse lentigines might release pressor amines., which could result in cardiomyopathy. Similarly, peptide release b y the lentigines could stimulate m y x o m a growth. To date, though, no peptide has b e e n identified. Thorough assessment o f a patient with profuse lentigines should be carried out even when there is no positi~,e f a m i l y or personal history. The report of this patient e m p h a s i z e s the need for giving special attention to the cardiovascular system, REFERENCES
1. Lamy M, De Grouchy J, Schweisguth O: Genetic and non-genetic factors in the etiology of congenital heart disease: A study of 1188 cases. Am J Hum Genet 9:1741, 1957, 2. Fomey WR, Robinson SJ, Pascoe DJ: Congenital heart disease, deafness and skeletal malformations: A new syndrome? J Pediatr 68:14-28, 1966. 3. Walther RJ: Cardiocutaneous syndrome. N Engl J Med 278:1127, 1968. 4. Gorlin RJ, Anderson RC, Blaw M: Multiple lentigines syndrome. Am J Dis Child 117:652-662, 1969.
Journal of the American Academy of Dermatology 5. Rees JR, Ross FGM, Keen G: Lentiginosis and left atrial myxoma. Br Heart J 35:874-876, 1973. 6. Selmanowitz VJ, Orentreich N, Felsestein JM: Lentiginosis profusa syndrome (multiple lentigines syndrome). Arch Dermatol 104:393-401, 1971. 7. Picketing D, Laski B, MacMillan DC, Rose V: "Little leopard" syndrome: Description of three cases and review of 24. Arch Dis Child 46:85-90, 1971. 8. Polani PE, Moynahan EJ: Progressive cardiomyopathic lentiginosis. Q J Med 41:205-225, !972. 9. Matthews NL: Lentige and electrocardiographic changes. N Engl J Med 278:780-781, 1968. 10. Norlund JJ, Lerner AB, Braverman IM, McGuire JS: The multiple lentigines syndrome. Arch Dermatol 107: 259-261, i973. 11. Walther RJ, Polanski B J, Grots IA: Electrocardiographic abnormalities in a family with generalized lentigo, N Engl J Med 275:1220-1225, 1966. 12. Smith RF, Pulicicchio LU, Holmes AV: Generalized lentigo: Electrocardiographic abnormalities, conduction disorders and arrhythmia in three cases. Am J Cardiol 25:501-506, 1970. 13. Lynch PJ: Leopard syndrome. Arch Dermatol 101:119, 1970. 14. Moynahan EJ: Multiple symmetrical moles with psychic and somatic infantilism and genital hypoplasia. Proc R Soc Med 55:959-960, 1962. 15. Pipkin AC, Pipkin SB: A pedigree of generalized lentigo. J Hered 41:79-83, 1950.
IIIII
II Illl
Lentiginosis associated with a left atrial myxoma Lata3~ Len Peterson, M.D., and W. Scott Serrill, M.D.
Portland and Albany, OR A 14-year-old white male patient with lentiginosis was in congestive heart failure. He was noted to be redheaded, and the lentigines were especially concentrated on the face, including the lips. A two-dimensional echocardiogram revealed an orange-sized mobile mass in the left atrium. Cardiac surgery for removal of the left atrial myxoma was successful, and a complete recovery was made. This is the second report of lentiginosis associated with'a left atrial myxoma and the first in which the immediate family did not have similar pigmentary changes. Lentiginosis and associated cardiac manifestations are briefly reviewed. (J AM ACAD DERMATOL10: 337-340, 1984.)
Cardiocutaneous syndromes were first noted by Lamy et al 1 in 1957, when they reported an association of abnormal pigmentation, congenital heart disease, and deafness in reviewing 1,188 cases of congenital heart disease in children. Forney et al 2 in 1966 reported a similar syndrome that also included multiple osseous defects. Two years later Walther 3 coined the term "cardioeutaneous syndrome," which included lentiginosis profusa with numerous cardiac abnormalities. Finally, in 1969, Gorlin et al a proposed the term "leopard syndrome" for a complex of congenital malformations including lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis and other cardiac abnormalities, abnormal genitalia, retardation of growth, and deafness. The association of lentiginosis and left atrial myxoma was made by Rees et al 5 in 1973 in an 18-year-old redheaded male patient whose initial presentation was loss of consciousness and left From the Department of Dermatology, The Oregon Health Sciences University, Portland. Reprint requests to: Dr. Larry Len Peterson, The Oregon Health Sciences University, Department of Dermatology, 3181 S.W. Sam Jackson Park Rd., Portland, OR 97201.
hemiparesis. He had previously been in good health with normal development. His mother and maternal uncle shared a similar pattern of lentigines with him. This is the second report of lentiginosis and left atrial myxoma and the first in which no positive family history for lentiginosis was obtainable. CASE REPORT The patient was a 14-year-old white boy with an unremarkable past history. Specifically, the patient's growth and his mental and sexual development appeared normal. He stated that his "freckles" had been present as long as he could remember and were present all year around. The time of admission to the hospital was February. He had been well until 4 weeks prior to admission, when he experienced pounding of the chest and dyspnea after running half of a lap in the gymnasium. Two weeks prior to admission he had acquired influenza-like symptoms, including malaise, fatigue, sore throat, a mildly productive cough, and a temperature elevated to 390 C. Later, myalgias, chest pain, and vomiting after meals ensued. He was seen by his family practitioner, and a hematocrit of 31% was noted. Iron supplementation was initiated, and a referral to a dermatologist for the numerous pigmented spots on his face was made. The dermatologist made the possible 337
338
Peterson and Serrill
Journal of the American Academy of Dermatology
Fig. 2. Two-dimensional echocardiogram demonstrating prolapse of left atrial myxoma (M) through the mitral valve (my) into the left ventricle (Iv). rv: Right ventricle; ra: right atrium; la: left atrium.
Fig. 1. Face showing numerous lentigines. association between the patient's lentigines and a cardiac abnormality after a murmur was auscultated. The patient was admitted to the university hospital. Physical examination revealed an ill-appearing youth with congestive heart failure. Pulse was 104 beats/min, respiratory rate 18/min, and blood pressure 110/64 mm Hg, and the patient was afebrile. Red hair, fair skin, and abundant lentigines were present on the face and lips (Fig. 1), upper back, chest, and arms. The lesions were brown to very brown. The remainder of the physical examination was noteworthy for a decrease in resonance on percussion and a decrease in breath sounds on auscultation in both bases. A hyperdynamic precordium was visible, with the point of maximal impulse at the sixth intercostal space, 11 cm lateral to the left sternal border. Cardiac examination revealed a grade 3/6 holosystolic murmur, +2 pitting edema to the knees, and jugular venous distension. The liver was tender and was determined to be 6 cm below the right costal margin. The remainder of the physical examinatibn was normal. The patient was not hyperteloric by facial measurement, and there was no apparent hearing loss, although audiometric testing was not done. No hypospadias was noted.
An electrocardiogram showed left atrial enlargement and sinus tachycardia. The chest x-ray film was consistent with congestive heart failure with bilateral pulmonary effusions and cardiomegaly. Laboratory data included normal serum chemistry except the following: blood urea nitrogen, 35 mg/dl; total bilirubin, 3.9 mg/dl; direct bilimbin, 2.1 mg/dl; alkaline phosphatase, 234 [U/liter; lactate dehydrogenase, 538%; and serum glutamic-oxaloacetic transaminase, 1,128 U/ml. Other abnormal values were as follows: prothrombin time, 25.4; partial thromboplastin time, 66.8; white blood cell count, 11,800; hematocrit, 37.6% with microcytic indices; polymorphonuclear neutrophils, 79; lymphocytes, 14; bands, 10; monocytes, 3; erythrocyte sedimentation rate, 1; platelets, 377,000; iron, 15 p.g/dl; iron-binding capacity, 307 ~g/dl; fibrinogen, 88 mg/dl; urinalysis with 1 + bilirubin and 30 mg/dl protein; elevated antistreptolysin O (ASO), 1:480; negative antinuclear antibody; and negative blood cultures. A two-dimensional echocardiogram revealed an orange-sized tumor located in the left atrium and freely falling into the left ventricle (Fig. 2). The patient underwent open-heart surgery in which an atrial myxoma was successfully removed, and a mitral valve annuloplasty was subsequently performed. The patient made a successful, uneventful recovery. Multiple skin biopsies examined postoperatively were consistent with lentiginosis (Fig. 3). The patient's mother was examined for any manifestations of the leopard syndrome, and none were apparent. The patient was an only child. When he was born, his mother was 35 years old and his father was 40 years
Volume 10 Number 2, Part 2 February, 1984
Lentiginosis associated with atrial myxoma
339
Fig. 3. Skin biopsy of lentigo, showing epidermal hyperplasia with thin, elongated rete ridges and hyperpigmentation of basal layer. (Hematoxylin-eosin stain; original magnification, • old. The father died of undiagnosed "heart trouble" 3 years after our patient was born. No autopsy was performed. DISCUSSION
The association between lentiginosis and cardiac abnormalities has been well established2 -14 These abnormalities are listed in Table I. This is only the second report involving an atrial myxoma. Our case is strikingly similar to the first case reported. Similarities include (1) redheadedness, (2) fair skin, (3) diagnosis of myxoma in teenage years, (4) normal growth and development, and (5) heavy facial involvement of lentigines. Conversely, no positive family history of lentigines was obtainable in this patient. This is puzzling because the mode of inheritance of the leopard syndrome has been reported to be autosomal dominant with variable expressivity. 1'~ Whether this syndrome was present in our patient is uncertain. His case may represent a form of spontaneous mutation, since both parents were relatively old at the time of his birth. Other alternative explanations include a failure to diagnose the syndrome in the parents because of mild expression (the father's
Table I. Cardiac abnormalities associated with lentiginosis 1. 2. 3. 4. 5. 6. 7. 8.
Axis deviations G Unilateral or bilateral hypertrophy 7"~ Prolonged PR interval s Left anterior hemiblock 1~ Bundle-branch block 1~ Complete heart block t2 Valvular disease r'la Endomyocardial fibroelastosis and obstructive cardiomyopathy~4 9. Left atrial myxorna ~
"heart condition" may have been the only sign), nonpaternity, a nongenetic disorder (phenocopy), and an association with a different genetic disorder (genocopy). It is likely that with an elevated ASO titer and elevated temperature, the patient probably had a concurrent streptococcal infection exacerbating his congestive heart failure. Liver congestion would be one way of explaining his abnormal liver functions. Why is there an association of lentigines and cardiac abnormalities? Selmanowitz et al ~ have suggested a possibie mutation in the embryonic
340
Peterson and Serrill
neural crest that c o u l d account for melanocytic ~ilterations and cardiac abnormalities. Alternatively, Polani and M o y n a h a n s h a v e proposed that the profuse lentigines might release pressor amines., which could result in cardiomyopathy. Similarly, peptide release b y the lentigines could stimulate m y x o m a growth. To date, though, no peptide has b e e n identified. Thorough assessment o f a patient with profuse lentigines should be carried out even when there is no positi~,e f a m i l y or personal history. The report of this patient e m p h a s i z e s the need for giving special attention to the cardiovascular system, REFERENCES
1. Lamy M, De Grouchy J, Schweisguth O: Genetic and non-genetic factors in the etiology of congenital heart disease: A study of 1188 cases. Am J Hum Genet 9:1741, 1957, 2. Fomey WR, Robinson SJ, Pascoe DJ: Congenital heart disease, deafness and skeletal malformations: A new syndrome? J Pediatr 68:14-28, 1966. 3. Walther RJ: Cardiocutaneous syndrome. N Engl J Med 278:1127, 1968. 4. Gorlin RJ, Anderson RC, Blaw M: Multiple lentigines syndrome. Am J Dis Child 117:652-662, 1969.
Journal of the American Academy of Dermatology 5. Rees JR, Ross FGM, Keen G: Lentiginosis and left atrial myxoma. Br Heart J 35:874-876, 1973. 6. Selmanowitz VJ, Orentreich N, Felsestein JM: Lentiginosis profusa syndrome (multiple lentigines syndrome). Arch Dermatol 104:393-401, 1971. 7. Picketing D, Laski B, MacMillan DC, Rose V: "Little leopard" syndrome: Description of three cases and review of 24. Arch Dis Child 46:85-90, 1971. 8. Polani PE, Moynahan EJ: Progressive cardiomyopathic lentiginosis. Q J Med 41:205-225, !972. 9. Matthews NL: Lentige and electrocardiographic changes. N Engl J Med 278:780-781, 1968. 10. Norlund JJ, Lerner AB, Braverman IM, McGuire JS: The multiple lentigines syndrome. Arch Dermatol 107: 259-261, i973. 11. Walther RJ, Polanski B J, Grots IA: Electrocardiographic abnormalities in a family with generalized lentigo, N Engl J Med 275:1220-1225, 1966. 12. Smith RF, Pulicicchio LU, Holmes AV: Generalized lentigo: Electrocardiographic abnormalities, conduction disorders and arrhythmia in three cases. Am J Cardiol 25:501-506, 1970. 13. Lynch PJ: Leopard syndrome. Arch Dermatol 101:119, 1970. 14. Moynahan EJ: Multiple symmetrical moles with psychic and somatic infantilism and genital hypoplasia. Proc R Soc Med 55:959-960, 1962. 15. Pipkin AC, Pipkin SB: A pedigree of generalized lentigo. J Hered 41:79-83, 1950.