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Leopard syndrome with manic psychosis
CASE REPORT
DOYNE W. LOYD, M.D. MING T. TSUANG, M.D., Ph.D.
Leopard syndrome with manic psychosis Multiple lentigines (or leopard) syndrome is a complex developmental disorder with defects in a variety of organ $)'stems. Gortin and associatesl suggested in 1969 that inultiple lentigines (freckles) accompanied by developnient~1 defects constituted a hereditary syndrome, for which they coined the mnemonic term "Leopard": L-Ientigines (multiple); E-electrocardiographic abnormalities; O-ocular hypertelorism; P-pulmonary stenosis; A-abnormalities of genitalia; R-retardation of growth; and D-deafness (sensori-neural)-the central features of this syndrome. Voron and associates2 reviewed 80 cases presented in the literature prior to 1976. They reported no psychiatric disorders with the exception of mental retardation. Kuhn and associates3 described a patient with intermittent depression. Galaction-Nitelea and Dociu4 found a family with multiple lentigines syndrome, psychopathy, alcoholism, and mental retardation. We observed a patient with multiple lentigines syndrome who also had mitral valve prolapse, Gilbert's disease (a benign hereditary hyperbilirubinemia), and a mania-like psychosis-three disorders that have not been previously associated with leopard syndrome. Dr. Loyd is a resident in psychiatry and Dr. Tsuang is prOfessor ofpsychiatry at the University of Iowa College of Medicine; Dr. Tsuang is also chiefstaffpsychiatrist, East Ward Inpatient Service, University of Iowa Psychiatric Hospital. Reprint requests to Dr. Tsuang at the Hospital, 500 Newton Road. Iowa City. fA 52242. OCTOBERI~'VOL21'NOIO
Case report A 26-year-old man was referred to the University of Iowa Psychiatric Hospital because of "confusion." He had been hospitalized twice for psychiatric illness. His first psychiatric hospitalization, at age 18, followed an episode during which he seemed disoriented to person and place and was unable to identify family members. The family described him then as nervous and pacing. Hospital records indicate that on admission he was mute and negativistic. He was incontinent at times during the hospitalization. Psychological testing revealed an 10 of 64. At discharge six weeks later, all these symptoms were absent and he was pleasant and sociable. He returned to his special education classes and was able to complete high school. His second episode occurred one year later, at age 19. Several days before hospitalization he became talkative and nervous. Just prior to admission he claimed to be lost and could not find his bed at home. He was agitated, hyperactive, and destructive to Objects during his hospitalization, and believed that everyone was against him. He recovered from these symptoms in two months and was able to attend job training courses, work as a custodian for three years, and live independently. Two weeks before the current admission, he became more talkative. Three. days prior to admission, he complained of becoming lost in a familiar part of town. Subsequently he seemed disoriented from time to time. During the initial interview the patient grinned broadly and laughed at most of the examiner's questions. He knew who he was but misstated the date by 17 months and said that he was in Mexico. At times, however, he would respond appropriately to questions on orientation. At the end of the examination he was also able to recall parts of the exami-
Case report nation that occurred earlier while he had been apparently disoriented. After a lengthy interview it appeared to us that he was not confused. The first night on the ward the patient slept only one hour, threw objects, ripped a bulletin board off a wall, paced, banged on walls, and laughed inappropriately. He did not become lost on the ward like a typical delirious patient. He remained hyperactive, distractible, and destructive for several days. Once he began taking haloperidol and lithium carbonate, he became cooperative and sociable, and remained consistently oriented to person, place, and time. Then he admitted to having had an elevated mood and racing thoughts on admission. Physical examination revealed a 187 em, 79.5 kg male with hundreds of dark brown 3- to 4-mm macules over most of his body. A few were several em in size. Mucous membranes were spared. The skin was hyperelastic. The patient had ptosis on the left, pectus excavatum, a broad nasal root, and a grade 4 to 6 systolic ejection murmur heard best at the apex with a thrill. He also had pes cavus and hyperkeratotic areas on the plantar surfaces of his feet. Biceps, triceps, brachioradial, and Achilles reflexes were equivocally trace. Knee jerks were 1 + bilaterally. The patient had difficulty with tandem walk and a mildly unsteady gate, but according to his father he had always walked that way. Total bilirubin was mildly elevated with a normal direct fraction. Reticulocyte count was normal. Radiologic findings on PA and lateral chest 1ilms were pectus excavatum and pulmonary vascular prominence at the hila. ECG abnormalities were first degree A-V block, left axis deviation with left anterior hemiblock, and incomplete right bundlebranch block. These findings were essentially the same as those of an ECG done eight years earlier. Biopsy of one of the brown macules showed lentigo simplex with giant melanosomes; dermatology consultants diagnosed leopard syndrome. Medicine consultants noted a grade 2 to 4 systolic murmur with midsystolic click. An echocardiogram showed mitral valve prolapse but otherwise was normal. Radionuclide angiogram and ventriculogram were both normal. The increased total bilirubin with a normal direct fraction was felt to be consistent with Gilbert's disease. The family history was positive for mental disorder. An older brother, age 28, had been hospitalized seven times for episodes of euphoria, hyperactivity, decreased sleep, aggressiveness, incoherent and increased verbalization, and disorientation. In each episode, all of the symptoms resolved after two to four months of hospitalization. The patient's half-brother, age 38, had been hospitalized for a similar psychosis.
Discussion Precise psychiatric diagnosis is difficult in the presence of mental retardation. Elevated mood. hyperactivity.
decreased sleep. distractibility. and racing thoughts are consisient with mania. Furthermore. the patient's previous psychiatric illnesses were also suggestive of affective disorder. And because he seemed confused. organic brain syndrome could not be immediately ruled out. Several things suggested that this patient did not have clouded consciousness: he was able to recall parts of the psychiatric examination that occurred while he was disoriented. he played cards appropriately with his family. and he did not become lost on the ward. These observations revealed a more intact intellect than the initial examination demonstrated. History. physical examination. and laboratory work did not indicate evidence of organic mental disorder. When the manic symptoms were completely resolved with antipsychotic treatment. we concluded that the psychiatric illness was not an organic mental disorder. The presence of mitral valve prolapse. Gilbert's disease. and mania with multiple lentigines syndrome may be coincidental. Gilbert's disease has been found in approximately 5% of healthy college students.s Mitral valve prolapse is also quite common; Devereux and associates6 report an incidence of approximately 6% in normal females. The incidence is somewhat less in males. The incidence of mania is probably about 0.8%.7 The coincidental occurrence of four apparently unrelated familial disorders in one patient is unlikely. If the brothers with symptoms of psychiatric disorders had been evaluated for multiple lentigines syndrome. mitral valve prolapse. and Gilbert's disease. ihe link between the four abnormalities would perhaps have been clarified. The family denied freckling on any of the other family members. Small numbers oflentigines and other nondisabling abnormalities in this syndrome may not have been noticed. however. so the family's statement was inconclusive. It would therefore have been worthwhile to conduct a personal examination of these family members. 0
REFERENCES 1. Gorlin RJ, Anderson RC, Blaw M: Multiple lentigines syndrome: Complex comprising multiple lentigines, electrocardiograph conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalilies of genitalia, retardation of growth, sensorineural deafness and autosomal dominant hereditary pattern. Am J Dis Child 117:652-662.1969. 2. Voron DA. Hatfield HH, Kalkhoff RK: Multiple lentigines syndrome: Case report and review of the literature. Am J Mad 80:447-456.1976. 3. Kuhn H, Haensch R, Losse B, et al: Hypertrophischobstruktive Kardiomopalhie und Lentiginosis. Dtsch Mad Wochenschr 102:679-683, 1977. 4. Galaction-Nitelea 0, Dociu I: Lentiginoses et anomalies de developpement. Dermafologica 148:108-115.1974. 5. Bark PD. Wolkoff AW, Berlin Nt: Inborn errors of bilirubin metabolism. Med Clin North Am 51:803-816, 1975. 6. Devereux RB. Perloff JK, Reichek N. et al: Mitral valve prolapse. Circulation
54:13-14,1976. 7. Winokur G: Types of affective disorders. J NaN Mant Dis 158:82-96, 1973.
PSYCHOSOMATICS
DOYNE W. LOYD, M.D. MING T. TSUANG, M.D., Ph.D.
Leopard syndrome with manic psychosis Multiple lentigines (or leopard) syndrome is a complex developmental disorder with defects in a variety of organ $)'stems. Gortin and associatesl suggested in 1969 that inultiple lentigines (freckles) accompanied by developnient~1 defects constituted a hereditary syndrome, for which they coined the mnemonic term "Leopard": L-Ientigines (multiple); E-electrocardiographic abnormalities; O-ocular hypertelorism; P-pulmonary stenosis; A-abnormalities of genitalia; R-retardation of growth; and D-deafness (sensori-neural)-the central features of this syndrome. Voron and associates2 reviewed 80 cases presented in the literature prior to 1976. They reported no psychiatric disorders with the exception of mental retardation. Kuhn and associates3 described a patient with intermittent depression. Galaction-Nitelea and Dociu4 found a family with multiple lentigines syndrome, psychopathy, alcoholism, and mental retardation. We observed a patient with multiple lentigines syndrome who also had mitral valve prolapse, Gilbert's disease (a benign hereditary hyperbilirubinemia), and a mania-like psychosis-three disorders that have not been previously associated with leopard syndrome. Dr. Loyd is a resident in psychiatry and Dr. Tsuang is prOfessor ofpsychiatry at the University of Iowa College of Medicine; Dr. Tsuang is also chiefstaffpsychiatrist, East Ward Inpatient Service, University of Iowa Psychiatric Hospital. Reprint requests to Dr. Tsuang at the Hospital, 500 Newton Road. Iowa City. fA 52242. OCTOBERI~'VOL21'NOIO
Case report A 26-year-old man was referred to the University of Iowa Psychiatric Hospital because of "confusion." He had been hospitalized twice for psychiatric illness. His first psychiatric hospitalization, at age 18, followed an episode during which he seemed disoriented to person and place and was unable to identify family members. The family described him then as nervous and pacing. Hospital records indicate that on admission he was mute and negativistic. He was incontinent at times during the hospitalization. Psychological testing revealed an 10 of 64. At discharge six weeks later, all these symptoms were absent and he was pleasant and sociable. He returned to his special education classes and was able to complete high school. His second episode occurred one year later, at age 19. Several days before hospitalization he became talkative and nervous. Just prior to admission he claimed to be lost and could not find his bed at home. He was agitated, hyperactive, and destructive to Objects during his hospitalization, and believed that everyone was against him. He recovered from these symptoms in two months and was able to attend job training courses, work as a custodian for three years, and live independently. Two weeks before the current admission, he became more talkative. Three. days prior to admission, he complained of becoming lost in a familiar part of town. Subsequently he seemed disoriented from time to time. During the initial interview the patient grinned broadly and laughed at most of the examiner's questions. He knew who he was but misstated the date by 17 months and said that he was in Mexico. At times, however, he would respond appropriately to questions on orientation. At the end of the examination he was also able to recall parts of the exami-
Case report nation that occurred earlier while he had been apparently disoriented. After a lengthy interview it appeared to us that he was not confused. The first night on the ward the patient slept only one hour, threw objects, ripped a bulletin board off a wall, paced, banged on walls, and laughed inappropriately. He did not become lost on the ward like a typical delirious patient. He remained hyperactive, distractible, and destructive for several days. Once he began taking haloperidol and lithium carbonate, he became cooperative and sociable, and remained consistently oriented to person, place, and time. Then he admitted to having had an elevated mood and racing thoughts on admission. Physical examination revealed a 187 em, 79.5 kg male with hundreds of dark brown 3- to 4-mm macules over most of his body. A few were several em in size. Mucous membranes were spared. The skin was hyperelastic. The patient had ptosis on the left, pectus excavatum, a broad nasal root, and a grade 4 to 6 systolic ejection murmur heard best at the apex with a thrill. He also had pes cavus and hyperkeratotic areas on the plantar surfaces of his feet. Biceps, triceps, brachioradial, and Achilles reflexes were equivocally trace. Knee jerks were 1 + bilaterally. The patient had difficulty with tandem walk and a mildly unsteady gate, but according to his father he had always walked that way. Total bilirubin was mildly elevated with a normal direct fraction. Reticulocyte count was normal. Radiologic findings on PA and lateral chest 1ilms were pectus excavatum and pulmonary vascular prominence at the hila. ECG abnormalities were first degree A-V block, left axis deviation with left anterior hemiblock, and incomplete right bundlebranch block. These findings were essentially the same as those of an ECG done eight years earlier. Biopsy of one of the brown macules showed lentigo simplex with giant melanosomes; dermatology consultants diagnosed leopard syndrome. Medicine consultants noted a grade 2 to 4 systolic murmur with midsystolic click. An echocardiogram showed mitral valve prolapse but otherwise was normal. Radionuclide angiogram and ventriculogram were both normal. The increased total bilirubin with a normal direct fraction was felt to be consistent with Gilbert's disease. The family history was positive for mental disorder. An older brother, age 28, had been hospitalized seven times for episodes of euphoria, hyperactivity, decreased sleep, aggressiveness, incoherent and increased verbalization, and disorientation. In each episode, all of the symptoms resolved after two to four months of hospitalization. The patient's half-brother, age 38, had been hospitalized for a similar psychosis.
Discussion Precise psychiatric diagnosis is difficult in the presence of mental retardation. Elevated mood. hyperactivity.
decreased sleep. distractibility. and racing thoughts are consisient with mania. Furthermore. the patient's previous psychiatric illnesses were also suggestive of affective disorder. And because he seemed confused. organic brain syndrome could not be immediately ruled out. Several things suggested that this patient did not have clouded consciousness: he was able to recall parts of the psychiatric examination that occurred while he was disoriented. he played cards appropriately with his family. and he did not become lost on the ward. These observations revealed a more intact intellect than the initial examination demonstrated. History. physical examination. and laboratory work did not indicate evidence of organic mental disorder. When the manic symptoms were completely resolved with antipsychotic treatment. we concluded that the psychiatric illness was not an organic mental disorder. The presence of mitral valve prolapse. Gilbert's disease. and mania with multiple lentigines syndrome may be coincidental. Gilbert's disease has been found in approximately 5% of healthy college students.s Mitral valve prolapse is also quite common; Devereux and associates6 report an incidence of approximately 6% in normal females. The incidence is somewhat less in males. The incidence of mania is probably about 0.8%.7 The coincidental occurrence of four apparently unrelated familial disorders in one patient is unlikely. If the brothers with symptoms of psychiatric disorders had been evaluated for multiple lentigines syndrome. mitral valve prolapse. and Gilbert's disease. ihe link between the four abnormalities would perhaps have been clarified. The family denied freckling on any of the other family members. Small numbers oflentigines and other nondisabling abnormalities in this syndrome may not have been noticed. however. so the family's statement was inconclusive. It would therefore have been worthwhile to conduct a personal examination of these family members. 0
REFERENCES 1. Gorlin RJ, Anderson RC, Blaw M: Multiple lentigines syndrome: Complex comprising multiple lentigines, electrocardiograph conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalilies of genitalia, retardation of growth, sensorineural deafness and autosomal dominant hereditary pattern. Am J Dis Child 117:652-662.1969. 2. Voron DA. Hatfield HH, Kalkhoff RK: Multiple lentigines syndrome: Case report and review of the literature. Am J Mad 80:447-456.1976. 3. Kuhn H, Haensch R, Losse B, et al: Hypertrophischobstruktive Kardiomopalhie und Lentiginosis. Dtsch Mad Wochenschr 102:679-683, 1977. 4. Galaction-Nitelea 0, Dociu I: Lentiginoses et anomalies de developpement. Dermafologica 148:108-115.1974. 5. Bark PD. Wolkoff AW, Berlin Nt: Inborn errors of bilirubin metabolism. Med Clin North Am 51:803-816, 1975. 6. Devereux RB. Perloff JK, Reichek N. et al: Mitral valve prolapse. Circulation
54:13-14,1976. 7. Winokur G: Types of affective disorders. J NaN Mant Dis 158:82-96, 1973.
PSYCHOSOMATICS