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Laurence-Moon Syndrome?: Dr. Whitaker replies
Letters Laurence-Moon Syndrome?
Dr. Whitaker replies
I read with interest the case report entitled "The Pituitary Gland in the Laurence-Moon Syndrome," which was written by Whitaker and associates and published in the March 1987 issue of the Proceedings (pages 216 to 222). The patient described was a 17-yearold boy who had had the onset of ptosis in childhood, progressive external ophthalmoplegia, progressive sensorineural hearing loss, gait disturbance (was this ataxia?), learning disabilities, and possibly a cardiac conduction defect (given his history of syncopal episodes and sudden death from cardiac arrest). Pigmentary disturbance of the retina was noted, but no data on vision, visual fields, or electroretinography were mentioned. This patient's clinical course is characteristic of the "Kearns-Sayre syndrome"; in fact, the authors indicated that certain aspects of this case had previously been reported by Kearns and Sayre. 1 The Kearns-Sayre syndrome is now recognized as one of the mitochondrial myopathies, 2 in which characteristic changes of mitochondria are observed by electron microscopy.
Dr. Pagon has raised an important issue about the nosology of the Laurence-Moon syndrome. Much confusion has arisen as a result of various phenotypic additions to the original Laurence-Moon description; in our article, my coauthors and I carefully attempted to avoid some of this confusion. Dr. Pagon has correctly described the Laurence-Moon-Biedl syndrome; we do not believe that our patient had this disorder. As indicated in the first paragraph of our report, we were describing a patient with the Laurence-Moon syndrome only; obesity and digital anomalies are not part of the original Laurence-Moon description. Data on the patient's vision were included in the article. As indicated, visual acuity was decreased bilaterally at 20/60 for the left eye and 20/40 for the right eye. Bilateral temporal visual field defects were present; visual field assessment was undertaken with use of Goldmann perimetry, and the loss of fields was thought to be characteristic of pigmentary degeneration of the retina. No data on electroretinography were available. There was no question that this patient had a pigmentary retinopathy. Although the funduscopic examination suggested that retinitis pigmentosa was present, histologic review showed a posterior pigment epitheliopathy, the features of which were not those of retinitis pigmentosa. Pigmentary retinopathy is of itself nonspecific; the diagnosis depends on the ophthalmologic findings considered together with other phenotypic manifestations. As a result, we believe that the patient had the Laurence-Moon syndrome; however, several features, including progressive external ophthalmoplegia and likely cardiac conduction abnormalities, are suggestive of the Kearns-Sayre syndrome. As emphasized by Eagle and associates, 1 the retinal changes of the Kearns-Sayre syndrome are those of a pigmentary retinopathy that typically involves the posterior fundus; indeed, in the case we described, the alterations involved the posterior fundus. Because of the constellation of abnormalities in this patient, we suggest that our case represents an overlap of the Laurence-Moon and Kearns-Sayre syndromes.
In contrast, the Laurence-Moon-Biedl syndrome is an autosomal recessive disorder characterized by (1) postaxial polydactyly, (2) mental retardation, (3) obesity, (4) a retinitis pigmentosa-like retinal dystrophy, (5) hypogonadism, and (6) interstitial nephritis. Ptosis, progressive external ophthalmoplegia, progressive sensorineural hearing loss, and cardiac conduction defects are not a part of this syndrome. None of the data presented on this patient suggests the diagnosis of the Laurence-Moon-Biedl syndrome. Perhaps if muscle tissue is available, it would be possible to do light microscopy or electron microscopy to evaluate for a mitochondrial myopathy. Roberta A. Pagon, M.D. Department of Pediatrics University of Washington School of Medicine Children's Orthopedic Hospital and Medical Center Seattle, Washington REFERENCES 1. Kearns TP, Sayre GP: Retinitis pigmentosa, external ophthalmoplegia, and complete heart block: unusual syndrome with histologic study in one of two cases. Arch Ophthalmol 60:280-289,1958 2. DiMauro S, Bonilla E, Zeviani M, Nakagawa M, DeVivo DC: Mitochondrial myopathies. Ann Neurol 17:521-538, 1985 Mayo Clin Proc 63:209-211,1988
The extraocular muscle tissues obtained at autopsy were reviewed by both light and electron microscopy. Because of autolytic changes, it was not possible to evaluate the specimens for the presence of a mitochondrial myopathy. Michael D. Whitaker, M.D.
209
210
LETTERS
REFERENCE 1. Eagle RC Jr, Hedges TR, Yanoff M: The atypical pigmentary retinopathy of Kearns-Sayre syndrome: a light and electron microscopic study. Ophthalmology 89:1433-1440, 1982
Amiodarone-Related Optic Neuropathy On reading Feiner and co-worker's description of 13 patients who had optic neuropathy during amiodarone therapy (reported in the August 1987 issue of the Proceedings, pages 702 to 717), we were surprised to encounter, in reference to our prior report of two similar patients, 1 the statement, "We disagree with their conclusions and believe that the disorder could be due to chance alone." In our article, we supported our assertion that the swelling of the optic disk and hemorrhages observed in three eyes of our two patients were a side effect of amiodarone, rather than coincidental ischemic optic neuropathy, with several arguments. First, although atypical cases have been reported, most recently by Slavin, 2 most patients with anterior ischemic optic neuropathy have at least arcuate field defects, which were absent in two of the three involved eyes in our patients. Also, the edema of the optic disk associated with anterior ischemic optic neuropathy rarely persists for as long as 3 months, as it did in our second patient, whose findings resolved only after the dosage of amiodarone had been decreased. Furthermore, other amphiphilic (or amphipathic) drugs (the class to which amiodarone belongs) have been implicated in optic neuropathies; the findings observed in patients receiving perhexiline are especially similar to those in our patients. The mechanism of the optic neuropathy remains to be determined. We propose the appellation "amiodarone papillopathy," because swelling of the optic disk has been present in all but one case (case 13 in the report by Feiner and colleagues) and because this designation leaves open the question about whether this is a toxic or an ischemic manifestation. Investigators have also noted some clinical similarities to the disk swelling observed in patients with juvenile diabetes, which has been termed "diabetic papillopathy." 3 The additional cases reported by Feiner and associates confirm the importance of the association between the administration of amiodarone and the occurrence of papillopathy and add to the clinical
Mayo Clin Proc, February 1988, Vol 63
spectrum patients with progressive and apparently permanent loss of vision. Both of our publications lend credence to the prediction by Morowitz4 that amphiphilic compounds such as amiodarone will be mentioned increasingly in the biomedical literature: "If you have not been informed of them before, ignore that journalistic omission; you will hear much of amphiphiles in years to come." John W. Gittinger, Jr., M.D. George K. Asdourian, M.D. University of Massachusetts Medical Center Worcester, Massachusetts REFERENCES 1. Gittinger JW Jr, Asdourian GK: Papillopathy caused by amiodarone. Arch Ophthalmol 105:349-351, 1987 2. Slavin ML: Chronic asymptomatic ischemic optic neuropathy: a report of two cases in adults with diabetes mellitus. J Clin Neuro Ophthalmol 7:198-201,1987 3. Appen RE, Chandra SR, Klein R, Myers FL: Diabetic papillopathy. Am J Ophthalmol 90:203-209, 1980 4. Morowitz HJ: Mayonnaise and the Origin of Life: Thoughts of Minds and Molecules. New York, Charles Scribner's Sons, 1985, p 30
Antimicrobial Agents Several points are worth clarifying in the article, "Tetracyclines, Chloramphenicol, Erythromycin, and Clindamycin," by Wilson and Cockerill in the October 1987 issue of the Proceedings (pages 906 to 915), because it is part of an excellent symposium on antimicrobial agents that will likely be quoted often. The dosages recommended for erythromycin in Table 3 (1 to 4 g every 6 hours orally and 1 to 2 g every 6 hours intravenously) are toxic and intolerable. The correct doses are 250 mg to 1 g and 500 mg to 1 g, respectively. The authors state that chancroid may be treated with tetracycline. The Centers for Disease Control no longer recommends this treatment, as most strains of Haemophilus ducreyi are resistant to tetracycline; 1,2 erythromycin, trimethoprim-sulfamethoxazole, or ceftriaxone, among other drugs, is acceptable therapy. The authors also suggest that "tetracycline may also be used in the treatment of gonococcal infections in patients unable to tolerate penicillin." Stamm and
Dr. Whitaker replies
I read with interest the case report entitled "The Pituitary Gland in the Laurence-Moon Syndrome," which was written by Whitaker and associates and published in the March 1987 issue of the Proceedings (pages 216 to 222). The patient described was a 17-yearold boy who had had the onset of ptosis in childhood, progressive external ophthalmoplegia, progressive sensorineural hearing loss, gait disturbance (was this ataxia?), learning disabilities, and possibly a cardiac conduction defect (given his history of syncopal episodes and sudden death from cardiac arrest). Pigmentary disturbance of the retina was noted, but no data on vision, visual fields, or electroretinography were mentioned. This patient's clinical course is characteristic of the "Kearns-Sayre syndrome"; in fact, the authors indicated that certain aspects of this case had previously been reported by Kearns and Sayre. 1 The Kearns-Sayre syndrome is now recognized as one of the mitochondrial myopathies, 2 in which characteristic changes of mitochondria are observed by electron microscopy.
Dr. Pagon has raised an important issue about the nosology of the Laurence-Moon syndrome. Much confusion has arisen as a result of various phenotypic additions to the original Laurence-Moon description; in our article, my coauthors and I carefully attempted to avoid some of this confusion. Dr. Pagon has correctly described the Laurence-Moon-Biedl syndrome; we do not believe that our patient had this disorder. As indicated in the first paragraph of our report, we were describing a patient with the Laurence-Moon syndrome only; obesity and digital anomalies are not part of the original Laurence-Moon description. Data on the patient's vision were included in the article. As indicated, visual acuity was decreased bilaterally at 20/60 for the left eye and 20/40 for the right eye. Bilateral temporal visual field defects were present; visual field assessment was undertaken with use of Goldmann perimetry, and the loss of fields was thought to be characteristic of pigmentary degeneration of the retina. No data on electroretinography were available. There was no question that this patient had a pigmentary retinopathy. Although the funduscopic examination suggested that retinitis pigmentosa was present, histologic review showed a posterior pigment epitheliopathy, the features of which were not those of retinitis pigmentosa. Pigmentary retinopathy is of itself nonspecific; the diagnosis depends on the ophthalmologic findings considered together with other phenotypic manifestations. As a result, we believe that the patient had the Laurence-Moon syndrome; however, several features, including progressive external ophthalmoplegia and likely cardiac conduction abnormalities, are suggestive of the Kearns-Sayre syndrome. As emphasized by Eagle and associates, 1 the retinal changes of the Kearns-Sayre syndrome are those of a pigmentary retinopathy that typically involves the posterior fundus; indeed, in the case we described, the alterations involved the posterior fundus. Because of the constellation of abnormalities in this patient, we suggest that our case represents an overlap of the Laurence-Moon and Kearns-Sayre syndromes.
In contrast, the Laurence-Moon-Biedl syndrome is an autosomal recessive disorder characterized by (1) postaxial polydactyly, (2) mental retardation, (3) obesity, (4) a retinitis pigmentosa-like retinal dystrophy, (5) hypogonadism, and (6) interstitial nephritis. Ptosis, progressive external ophthalmoplegia, progressive sensorineural hearing loss, and cardiac conduction defects are not a part of this syndrome. None of the data presented on this patient suggests the diagnosis of the Laurence-Moon-Biedl syndrome. Perhaps if muscle tissue is available, it would be possible to do light microscopy or electron microscopy to evaluate for a mitochondrial myopathy. Roberta A. Pagon, M.D. Department of Pediatrics University of Washington School of Medicine Children's Orthopedic Hospital and Medical Center Seattle, Washington REFERENCES 1. Kearns TP, Sayre GP: Retinitis pigmentosa, external ophthalmoplegia, and complete heart block: unusual syndrome with histologic study in one of two cases. Arch Ophthalmol 60:280-289,1958 2. DiMauro S, Bonilla E, Zeviani M, Nakagawa M, DeVivo DC: Mitochondrial myopathies. Ann Neurol 17:521-538, 1985 Mayo Clin Proc 63:209-211,1988
The extraocular muscle tissues obtained at autopsy were reviewed by both light and electron microscopy. Because of autolytic changes, it was not possible to evaluate the specimens for the presence of a mitochondrial myopathy. Michael D. Whitaker, M.D.
209
210
LETTERS
REFERENCE 1. Eagle RC Jr, Hedges TR, Yanoff M: The atypical pigmentary retinopathy of Kearns-Sayre syndrome: a light and electron microscopic study. Ophthalmology 89:1433-1440, 1982
Amiodarone-Related Optic Neuropathy On reading Feiner and co-worker's description of 13 patients who had optic neuropathy during amiodarone therapy (reported in the August 1987 issue of the Proceedings, pages 702 to 717), we were surprised to encounter, in reference to our prior report of two similar patients, 1 the statement, "We disagree with their conclusions and believe that the disorder could be due to chance alone." In our article, we supported our assertion that the swelling of the optic disk and hemorrhages observed in three eyes of our two patients were a side effect of amiodarone, rather than coincidental ischemic optic neuropathy, with several arguments. First, although atypical cases have been reported, most recently by Slavin, 2 most patients with anterior ischemic optic neuropathy have at least arcuate field defects, which were absent in two of the three involved eyes in our patients. Also, the edema of the optic disk associated with anterior ischemic optic neuropathy rarely persists for as long as 3 months, as it did in our second patient, whose findings resolved only after the dosage of amiodarone had been decreased. Furthermore, other amphiphilic (or amphipathic) drugs (the class to which amiodarone belongs) have been implicated in optic neuropathies; the findings observed in patients receiving perhexiline are especially similar to those in our patients. The mechanism of the optic neuropathy remains to be determined. We propose the appellation "amiodarone papillopathy," because swelling of the optic disk has been present in all but one case (case 13 in the report by Feiner and colleagues) and because this designation leaves open the question about whether this is a toxic or an ischemic manifestation. Investigators have also noted some clinical similarities to the disk swelling observed in patients with juvenile diabetes, which has been termed "diabetic papillopathy." 3 The additional cases reported by Feiner and associates confirm the importance of the association between the administration of amiodarone and the occurrence of papillopathy and add to the clinical
Mayo Clin Proc, February 1988, Vol 63
spectrum patients with progressive and apparently permanent loss of vision. Both of our publications lend credence to the prediction by Morowitz4 that amphiphilic compounds such as amiodarone will be mentioned increasingly in the biomedical literature: "If you have not been informed of them before, ignore that journalistic omission; you will hear much of amphiphiles in years to come." John W. Gittinger, Jr., M.D. George K. Asdourian, M.D. University of Massachusetts Medical Center Worcester, Massachusetts REFERENCES 1. Gittinger JW Jr, Asdourian GK: Papillopathy caused by amiodarone. Arch Ophthalmol 105:349-351, 1987 2. Slavin ML: Chronic asymptomatic ischemic optic neuropathy: a report of two cases in adults with diabetes mellitus. J Clin Neuro Ophthalmol 7:198-201,1987 3. Appen RE, Chandra SR, Klein R, Myers FL: Diabetic papillopathy. Am J Ophthalmol 90:203-209, 1980 4. Morowitz HJ: Mayonnaise and the Origin of Life: Thoughts of Minds and Molecules. New York, Charles Scribner's Sons, 1985, p 30
Antimicrobial Agents Several points are worth clarifying in the article, "Tetracyclines, Chloramphenicol, Erythromycin, and Clindamycin," by Wilson and Cockerill in the October 1987 issue of the Proceedings (pages 906 to 915), because it is part of an excellent symposium on antimicrobial agents that will likely be quoted often. The dosages recommended for erythromycin in Table 3 (1 to 4 g every 6 hours orally and 1 to 2 g every 6 hours intravenously) are toxic and intolerable. The correct doses are 250 mg to 1 g and 500 mg to 1 g, respectively. The authors state that chancroid may be treated with tetracycline. The Centers for Disease Control no longer recommends this treatment, as most strains of Haemophilus ducreyi are resistant to tetracycline; 1,2 erythromycin, trimethoprim-sulfamethoxazole, or ceftriaxone, among other drugs, is acceptable therapy. The authors also suggest that "tetracycline may also be used in the treatment of gonococcal infections in patients unable to tolerate penicillin." Stamm and