Ocular Findings in Turcot Syndrome (glioma-polyposis) PAUL M. MUNDEN, MD, WARREN M. SOBOL, MD, THOMAS A. WEINGEIST, MD, PhD
Abstract: Turcot syndrome is a hereditary condition characterized by multiple, adenomatous gastrointestinal polyps associated with neuroepithelial tumors of the central nervous system. The authors examined a patient with Turcot syndrome who had multiple regions of congenital hypertrophy of the retinal pigment epithelium (CHRPE) with areas of surrounding hypopigmentation in the fundi of both eyes. Multiple, bilateral patches of CHRPE have been reported in patients with familial adenomatous polyposis and Gardner syndrome. This finding is thought to be a sensitive and specific clinical marker for these conditions and useful for predicting the presence and development of colorectal polyposis. Our findings provide further evidence that familial adenomatous polyposis, Gardner syndrome, and Turcot syndrome may be related conditions representing the variable phenotypic expression of a single, autosomal dominant genetic disorder. Children and young adults with multiple patches of CHRPE and a family history of adenomatous polyposis may be at increased risk for the development of central nervous system tumors as well as gastrointestinal polyps. Ophthalmology 1991; 98: 111-114
The Turcot syndrome is a rare, hereditary condition in which there is an association between multiple adenomatous gastrointestinal polyps and neuroepithelial tumors of the central nervous system. 1 The mode of inheritance of Turcot syndrome has been debated and its distinction from the other hereditary gastrointestinal polyposis syndromes is not well defined. 2,3 Most authors consider Turcot syndrome, familial adenomatous polyposis, and Gardner syndrome to be common entities representing a variable phenotypic expression of a single, autosomal dominant genetic disorder. 4 - 7 Congenital hypertrophy of the retinal pigment epithelium (CHRPE) has been reported in association with familial adenomatous
Originally received: July 12, 1990. Revision accepted: October 9, 1990. From the Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City. Supported in part by an unrestricted grant from Research to Prevent Blindness, Inc, New York, New York. Reprint requests to Warren M. Sobol, MD, C. S. O'Brien Library, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA 52246.
polyposis8,9 and Gardner syndrome, 10-12 and the presence of multiple CHRPE lesions has been correlated with the presence and development of polyposis in these conditions. 4 ,13 We examined a patient with the clinical and histopathologic findings of Turcot syndrome. Results of his ocular examination showed multiple, bilateral CHRPE lesions of the fundus, a previously unreported finding.
CASE REPORT A 20-year-old white man presented to the Emergency Room at the University of Iowa Hospitals and Clinics with a 2-day history of headaches, nausea, and vomiting following closed head trauma with a brief period of loss of consciousness. His parents had noted increasing dysarthria, ataxia, and frequent falls over a period of several months prior to this accident. His past medical history was significant for an episode of lower gastrointestinal bleeding of uncertain etiology I year previously. His father and half-sister were affected with multiple polyps of the colon and both had undergone complete resection of the colon. There was no history of consanguinity between the parents. Physical examination results at the time of admission were remarkable for stable vital signs, equal and reactive pupils, and absence of papilledema. There were no cutaneous nodules noted on examination of the skin, however, a cafe-au-Iait spot was
111
OPHTHALMOLOGY
•
JANUARY 1991
noted over the left flank. Multiple rectal polyps were palpable on digital examination. Results of his neurologic examination showed an ataxic gait, and on Romberg testing he consistently fell to the left. Horizontal jerk nystagmus to the left was noted and horizontal saccades were hypermetric. Results of admission laboratory studies were significant for a hypochromic, microcytic anemia. Magnetic resonance imaging (Fig 1) and computed tomography (Fig 2) of the brain showed a large, left-sided cerebellar tumor that enhanced with contrast and gadolinium. A total-body bone scan gave negative results. Plain film radiographs of the teeth, mandible, and facial bones showed no caries, osteomas, or bony defects. A cerebrospinal fluid sample was positive for tumor cells. No evidence of metastatic tumor was found with bone marrow aspirate and biopsy. The patient underwent a posterior fossa craniotomy with complete resection of the tumor. Histopathologic examination results were consistent with a diagnosis of medulloblastoma (Fig 3). The postoperative course was uneventful and the patient recovered without development of additional neurologic deficits. He subsequently received·a full course of external beam radiotherapy to the craniospinal axis. After recovery from his surgery the patient underwent upper gastrointestinal endoscopy and flexible sigmoidoscopy. Numerous, small polyps were seen in the gastric fundus and throughout the duodenum. There were more than 1000 polyps scattered throughout the colon, ranging in size from 5 mm to 4 em (Fig 4). Two large, polypoid masses greater than 5 em in diameter were noted in the descending colon (Fig 5). Biopsies were taken at multiple sites. Results of histopathologic examination of the lesions showed tubular adenomas of the duodenum (Fig 6) and colon, as well as fundic gland polyps of the stomach. There was no evidence of carcinoma on any of the tissue sections. The patient presented to the General Ophthalmology clinic 4 months after his tumor resection for a routine ocular examination. His past ocular history was significant for a "scar" in the macula of the left eye, noted at age 11 during an optometric examination. Ocular examination results showed a best corrected visual acuity of 20/20 in each eye (Rx: -4.25 +4.00 X 105, right eye, and -5.00 +4.25 X 90, left eye). There was no afferent pupillary defect. Results of anterior segment examination and intraocular pressures were normal. Visual fields were full to confrontation. Ocular versions were full. Horizontal saccades were hypermetric and horizontal jerk nystagmus was noted on lateral gaze. Results of dilated fundus examination showed enlarged cup-to-disc ratios with healthy rims in both optic nerves. Numerous patches of typical CHRPE lesions with surrounding retinal pigment epithelium hypopigmentation were noted in both eyes (Figs 7, 9). These lesions were posterior in location, with one area ofCHRPE located in the central portion of the macula of the left eye (Fig 8).
DISCUSSION In 1959 Turcot and colleagues 1 reported two siblings with polyposis of the colon and central nervous system tumors. This association subsequently has become known as Turcot syndrome or the glioma-polyposis syndrome. 14 This is a rare condition; fewer than 60 cases have been reported, and only 34 (including the current case) have histopathologic confirmation of the diagnosis. 15 Specific descriptions of the ocular findings in Turcot syndrome are not given in the ophthalmic literature. We believe this constitutes the first case report of CHRPE 112
•
VOLUME 98
•
NUMBER 1
lesions in a patient with histopathologically confirmed Turcot syndrome. Our patient's findings included multiple CHRPE lesions in both fundi, as well as horizontal jerk nystagmus in lateral gaze and hypermetric saccades attributable to his posterior fossa tumor. Previous reports have noted the sequelae of the effects of an intracranial mass lesion, including papilledema,3,4.14,16,17 nystagmus,6 diplopia,14 dilated, nonreactive pupils,18 absent corneal reflex,18 decreased visual acuity, and ptosis. 3 Numerous, typical patches of CHRPE have been briefly described in a 15-year-old girl with glioblastoma of the brain "at risk for Gardner's syndrome.,,7 Familial adenomatous polyposis is an autosomal dominant condition in which multiple, adenomatous polyps develop throughout the gastrointestinal tract early in life. Adenomas of the colon and rectum are common, with an extremely high incidence (up to 100%) of malignant transformation. Fundic gland polyps of the stomach and adenomas of the small intestine also occur. 2 Gardner syndrome is characterized by a similar degree and distribution of gastrointestinal polyposis in association with extracoIonic manifestations. These manifestations include benign soft-tissue or bone tumors (specifically osteomas of the skull and mandible), abnormal dentition, epidermal inclusion cysts, and desmoid tumors. 2 Other syndromes with gastrointestinal polyposis and associated malignancies are summarized in Table I. Multiple, bilateral CHRPE lesions have been reported in patients with both familial adenomatous polyposis4,8 and Gardner syndrome. lO,11 The finding of multiple CHRPE lesions in patients with a positive family history is thought to be a useful congenital phenotypic marker for the presence or development of colorectal adenomatous polyposis. 4,13 Our findings of multiple, bilateral CHRPE lesions in association with gastric fundus polyps and multiple adenomatous polyps in the small intestine and colon in this patient support the hypothesis that Turcot syndrome may be a related phenotypic manifestation of the same gene responsible for familial adenomatous polyposis and Gardner syndrome. Ophthalmologists should be aware of Turcot syndrome as it relates to multiple, bilateral CHRPE fundus lesions and the spectrum of familial adenomatous polyposis and Gardner syndrome. The presence of bilateral, multiple CHRPE lesions is known to be a congenital phenotypic marker for these conditions and may be useful for predicting the development or presence of their colonic or extracolonic manifestations. Children and young adults with multiple patches of CHRPE and a family history of familial adenomatous polyposis may be at increased risk for the development of central nervous system tumors as well as gastrointestinal polyps. The ophthalmologist is in a unique position to seek out specific neuro-ophthalmic signs of an intracranial tumor when multiple CHRPE lesions are noted in association with a hereditary gastrointestinal polyposis syndrome. The embryonal brainstem malignancies, glioblastoma and medulloblastoma, may occur either as new genetic mutations or in conjunction with a family history of familial adenomatous polyposis or Gardner syndrome. Because of the poor survival associated with these brainstem
MUNDEN et al
•
OCULAR FINDINGS IN TURCOT SYNDROME
Fig 1. Top left, sagittal section magnetic resonance image demonstrates large, well-delineated, enhancing cerebellar tumor. Fig 2. Top right, computed tomography shows an enhancing posterior fossa mass centered over the cerebellar vermis with compression of the fourth ventrical. Partial calcification is evident within the mass. Fig 3. Second row left, photomicrograph shows neoplastic medulloblastoma cells with oval, dark-staining nuclei. Individual cell necrosis is prominent and mitotic figures are seen (hematoxylineosin; original magnification, X100). Fig 4. Second row right, endoscopic photograph of multiple colonic polyps. Fig 5. Third row left, endoscopic photograph of large polyps in descending colon at 40 cm. Fig 6. Third row right, photomicrograph of duodenal polyp biopsy showing a tubular adenoma without evidence of malignant transformation (hematoxylineosin, original magnification, X I00). Fig 7. Fourth row left, posterior retina showing triangular patch of CHRPE with surrounding hypopigmentation. Fig 8. Fourth row right, hypopigmented CHRPE lesion in the macula of the left eye. Fig 9. Bottom, mid periphery of retina showing small, oval patch of CHRPE and adjacent "comet-tail" hypopigmented lesion.
113
OPHTHALMOLOGY
•
JANUARY 1991
•
VOLUME 98
•
NUMBER 1
Table 1. Clinical Characteristics and Ocular Findings in the Inherited Gastrointestinal Polyposis Syndromes Gastrointestinal Lesions
Extraintestinal Lesions
Ocular Findings
Predisposition to Cancer
Adenomatous Polyposis Syndromes Familial adenomatous polyposis (AD)
Multiple (> 100) gastrointestinal polyps mainly in colon and rectum
None
CHRPE
Colon adenocarcinoma in all untreated patients2
Gardner syndrome (AD)
Same as familial adenomatous polyposis
Osteomas of the skull and mandible, epidermoid and dentigerous cysts, lipomas, fibromas, and desmoid tumors
CHRPE
Colon adenocarcinoma in all untreated patients, other cancers also reported (e.g., thyroid, liver, brain)2.5
Turcot's syndrome (considered AD by most authors, AR by otherst4,6
Same as familial adenomatous polyposis
Neuroepithelial brain tumors (medulloblastoma, glioblastoma)
CHRPE, neuroophthalmic signs of intracranial tumor
Colon adenocarcinoma, ileal reticulum cell sarcoma, and thyroid papillary carcinoma have been reported in association .15,18
Hamartomatous PolYPOSis Syndromes Peutz-Jeghers syndrome (AD)
Multiple (few to hundreds) gastrointestinal polyps, most frequently in small bowel
Melanin spots on lips, buccal mucosa, and digits. Hamartomas of other mucosal surfaces (nose, esophagus, bronchus)
Pigmentation of lids and conjunctiva
GI tract and other cancers in up to 48% of cases 2
Familial juvenile polyposis (AD)
Multiple gastrointestinal polyps, most frequently in colon and rectum
None
None
Probable, but magnitude of risk unknown 2
AD
=
autosomal dominant; CHRPE
=
congenital hypertrophy of the retinal pigment epithelium; AR
tumors, some individuals may not survive to the development of polyposis or any of the extracolonic manifestations of these inherited conditions. Consequently, all individuals with these central nervous system malignancies and any history suggestive of familial adenomatous polyposis should have a complete ophthalmic examination.
REFERENCES 1. Turcot J, Despres J-P, St. Pierre F. Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases. Dis Colon Rectum 1959; 2:465-8. 2. Haggitt RC, Reid BJ. Hereditary gastrOintestinal polyposis syndromes. Am J Surg Patho11986; 10:871-87. 3. Itoh H, Ohsato K, Yao T, et al. Turcot's syndrome and its mode of inheritance. Gut 1979; 20:414-9. 4. Romania A, lakov IN, McGannon E, et al. Congenital hypertrophy of the retinal pigment epithelium in familial adenomatous polyposis. Ophthalmology 1989; 96:879-84. 5. Smith WG, Kem BB. The nature of the mutation in familial multiple polyposis: papillary carcinoma of the thyroid, brain tumors, and familial multiple polyposis. Dis Colon Rectum 1973; 16:264-71. 6. Jarvis L, Bathurst N, Mohan D, Beckly D. Turcot's syndrome: a review. Dis Colon Rectum 1988; 31:907-14. 7. Traboulsi EI, Maumenee IH, Krush AJ, et al. Pigmented ocular fundus lesions in the inherited gastrointestinal polyposis syndromes and in hereditary non polyposis colorectal cancer. Ophthalmology 1988; 95: 964-9.
114
=
autosomal recessive.
8. Berk T, Cohen l, McLeod RS, Parker JA. Congenital hypertrophy of the retinal pigment epithelium as a marker for familial adenomatous polyposiS. Dis Colon Rectum. 1988; 31 :253-7. 9. Diaz-Llopis M, Menezo JL. Congenital hypertrophy of the retinal pigment epithelium in familial adenomatous polyposiS. Arch Ophthalmol 1988; 106:412-3. 10. Lewis RA, Crowder WE, Eierman LA, et al. The Gardner syndrome: significance of ocular features. Ophthalmology 1984; 91 :916-25. 11. Blair NP, Trempe CL. Hypertrophy of the retinal pigment epithelium associated with Gardner's syndrome. Am J Ophthalmol 1980; 90: 661-7. 12. Traboulsi EI, Krush AJ, Gardner EJ, et al. Prevalence and importance of pigmented ocular fundus lesions in Gardner's syndrome. N Engl J Med 1987; 316:661-7. 13. Traboulsi EI, Maumenee IH, Krush AJ, et al. Congenital hypertrophy of the retinal pigment epithelium predicts colorectal polYPOSis in Gardner's syndrome. Arch Ophthalmol1990; 108:525-6. 14. Baughman FA, List CF, Williams JR, et al. The glioma· polyposis syndrome. N Engl J Med 1969; 281:1345-6. 15. Jamjoom lAB, Sadiq S, Motti AB, et al. Turcot syndrome: report of a case and review of the literature. Int Surg 1989; 74:45-50. 16. Rothman D, Su CP, Kendall AB. Dilemma in a case of Turcot's (gliomapolyposis) syndrome: report of a case. Dis Colon Rectum 1975; 18: 514-5. 17. Chowdhary UM, Boehme DH, AI-Jishi M. Turcot syndrome (glioma polyposis). Case report. J Neurosurg 1985; 63:804-7. 18. Schroder S, Moehrs D, von Weltzien J, et al. The Turcot syndrome: report of an additional case and review of the literature. Dis Colon Rectum 1983; 26:533-8.
Abstract: Turcot syndrome is a hereditary condition characterized by multiple, adenomatous gastrointestinal polyps associated with neuroepithelial tumors of the central nervous system. The authors examined a patient with Turcot syndrome who had multiple regions of congenital hypertrophy of the retinal pigment epithelium (CHRPE) with areas of surrounding hypopigmentation in the fundi of both eyes. Multiple, bilateral patches of CHRPE have been reported in patients with familial adenomatous polyposis and Gardner syndrome. This finding is thought to be a sensitive and specific clinical marker for these conditions and useful for predicting the presence and development of colorectal polyposis. Our findings provide further evidence that familial adenomatous polyposis, Gardner syndrome, and Turcot syndrome may be related conditions representing the variable phenotypic expression of a single, autosomal dominant genetic disorder. Children and young adults with multiple patches of CHRPE and a family history of adenomatous polyposis may be at increased risk for the development of central nervous system tumors as well as gastrointestinal polyps. Ophthalmology 1991; 98: 111-114
The Turcot syndrome is a rare, hereditary condition in which there is an association between multiple adenomatous gastrointestinal polyps and neuroepithelial tumors of the central nervous system. 1 The mode of inheritance of Turcot syndrome has been debated and its distinction from the other hereditary gastrointestinal polyposis syndromes is not well defined. 2,3 Most authors consider Turcot syndrome, familial adenomatous polyposis, and Gardner syndrome to be common entities representing a variable phenotypic expression of a single, autosomal dominant genetic disorder. 4 - 7 Congenital hypertrophy of the retinal pigment epithelium (CHRPE) has been reported in association with familial adenomatous
Originally received: July 12, 1990. Revision accepted: October 9, 1990. From the Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City. Supported in part by an unrestricted grant from Research to Prevent Blindness, Inc, New York, New York. Reprint requests to Warren M. Sobol, MD, C. S. O'Brien Library, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA 52246.
polyposis8,9 and Gardner syndrome, 10-12 and the presence of multiple CHRPE lesions has been correlated with the presence and development of polyposis in these conditions. 4 ,13 We examined a patient with the clinical and histopathologic findings of Turcot syndrome. Results of his ocular examination showed multiple, bilateral CHRPE lesions of the fundus, a previously unreported finding.
CASE REPORT A 20-year-old white man presented to the Emergency Room at the University of Iowa Hospitals and Clinics with a 2-day history of headaches, nausea, and vomiting following closed head trauma with a brief period of loss of consciousness. His parents had noted increasing dysarthria, ataxia, and frequent falls over a period of several months prior to this accident. His past medical history was significant for an episode of lower gastrointestinal bleeding of uncertain etiology I year previously. His father and half-sister were affected with multiple polyps of the colon and both had undergone complete resection of the colon. There was no history of consanguinity between the parents. Physical examination results at the time of admission were remarkable for stable vital signs, equal and reactive pupils, and absence of papilledema. There were no cutaneous nodules noted on examination of the skin, however, a cafe-au-Iait spot was
111
OPHTHALMOLOGY
•
JANUARY 1991
noted over the left flank. Multiple rectal polyps were palpable on digital examination. Results of his neurologic examination showed an ataxic gait, and on Romberg testing he consistently fell to the left. Horizontal jerk nystagmus to the left was noted and horizontal saccades were hypermetric. Results of admission laboratory studies were significant for a hypochromic, microcytic anemia. Magnetic resonance imaging (Fig 1) and computed tomography (Fig 2) of the brain showed a large, left-sided cerebellar tumor that enhanced with contrast and gadolinium. A total-body bone scan gave negative results. Plain film radiographs of the teeth, mandible, and facial bones showed no caries, osteomas, or bony defects. A cerebrospinal fluid sample was positive for tumor cells. No evidence of metastatic tumor was found with bone marrow aspirate and biopsy. The patient underwent a posterior fossa craniotomy with complete resection of the tumor. Histopathologic examination results were consistent with a diagnosis of medulloblastoma (Fig 3). The postoperative course was uneventful and the patient recovered without development of additional neurologic deficits. He subsequently received·a full course of external beam radiotherapy to the craniospinal axis. After recovery from his surgery the patient underwent upper gastrointestinal endoscopy and flexible sigmoidoscopy. Numerous, small polyps were seen in the gastric fundus and throughout the duodenum. There were more than 1000 polyps scattered throughout the colon, ranging in size from 5 mm to 4 em (Fig 4). Two large, polypoid masses greater than 5 em in diameter were noted in the descending colon (Fig 5). Biopsies were taken at multiple sites. Results of histopathologic examination of the lesions showed tubular adenomas of the duodenum (Fig 6) and colon, as well as fundic gland polyps of the stomach. There was no evidence of carcinoma on any of the tissue sections. The patient presented to the General Ophthalmology clinic 4 months after his tumor resection for a routine ocular examination. His past ocular history was significant for a "scar" in the macula of the left eye, noted at age 11 during an optometric examination. Ocular examination results showed a best corrected visual acuity of 20/20 in each eye (Rx: -4.25 +4.00 X 105, right eye, and -5.00 +4.25 X 90, left eye). There was no afferent pupillary defect. Results of anterior segment examination and intraocular pressures were normal. Visual fields were full to confrontation. Ocular versions were full. Horizontal saccades were hypermetric and horizontal jerk nystagmus was noted on lateral gaze. Results of dilated fundus examination showed enlarged cup-to-disc ratios with healthy rims in both optic nerves. Numerous patches of typical CHRPE lesions with surrounding retinal pigment epithelium hypopigmentation were noted in both eyes (Figs 7, 9). These lesions were posterior in location, with one area ofCHRPE located in the central portion of the macula of the left eye (Fig 8).
DISCUSSION In 1959 Turcot and colleagues 1 reported two siblings with polyposis of the colon and central nervous system tumors. This association subsequently has become known as Turcot syndrome or the glioma-polyposis syndrome. 14 This is a rare condition; fewer than 60 cases have been reported, and only 34 (including the current case) have histopathologic confirmation of the diagnosis. 15 Specific descriptions of the ocular findings in Turcot syndrome are not given in the ophthalmic literature. We believe this constitutes the first case report of CHRPE 112
•
VOLUME 98
•
NUMBER 1
lesions in a patient with histopathologically confirmed Turcot syndrome. Our patient's findings included multiple CHRPE lesions in both fundi, as well as horizontal jerk nystagmus in lateral gaze and hypermetric saccades attributable to his posterior fossa tumor. Previous reports have noted the sequelae of the effects of an intracranial mass lesion, including papilledema,3,4.14,16,17 nystagmus,6 diplopia,14 dilated, nonreactive pupils,18 absent corneal reflex,18 decreased visual acuity, and ptosis. 3 Numerous, typical patches of CHRPE have been briefly described in a 15-year-old girl with glioblastoma of the brain "at risk for Gardner's syndrome.,,7 Familial adenomatous polyposis is an autosomal dominant condition in which multiple, adenomatous polyps develop throughout the gastrointestinal tract early in life. Adenomas of the colon and rectum are common, with an extremely high incidence (up to 100%) of malignant transformation. Fundic gland polyps of the stomach and adenomas of the small intestine also occur. 2 Gardner syndrome is characterized by a similar degree and distribution of gastrointestinal polyposis in association with extracoIonic manifestations. These manifestations include benign soft-tissue or bone tumors (specifically osteomas of the skull and mandible), abnormal dentition, epidermal inclusion cysts, and desmoid tumors. 2 Other syndromes with gastrointestinal polyposis and associated malignancies are summarized in Table I. Multiple, bilateral CHRPE lesions have been reported in patients with both familial adenomatous polyposis4,8 and Gardner syndrome. lO,11 The finding of multiple CHRPE lesions in patients with a positive family history is thought to be a useful congenital phenotypic marker for the presence or development of colorectal adenomatous polyposis. 4,13 Our findings of multiple, bilateral CHRPE lesions in association with gastric fundus polyps and multiple adenomatous polyps in the small intestine and colon in this patient support the hypothesis that Turcot syndrome may be a related phenotypic manifestation of the same gene responsible for familial adenomatous polyposis and Gardner syndrome. Ophthalmologists should be aware of Turcot syndrome as it relates to multiple, bilateral CHRPE fundus lesions and the spectrum of familial adenomatous polyposis and Gardner syndrome. The presence of bilateral, multiple CHRPE lesions is known to be a congenital phenotypic marker for these conditions and may be useful for predicting the development or presence of their colonic or extracolonic manifestations. Children and young adults with multiple patches of CHRPE and a family history of familial adenomatous polyposis may be at increased risk for the development of central nervous system tumors as well as gastrointestinal polyps. The ophthalmologist is in a unique position to seek out specific neuro-ophthalmic signs of an intracranial tumor when multiple CHRPE lesions are noted in association with a hereditary gastrointestinal polyposis syndrome. The embryonal brainstem malignancies, glioblastoma and medulloblastoma, may occur either as new genetic mutations or in conjunction with a family history of familial adenomatous polyposis or Gardner syndrome. Because of the poor survival associated with these brainstem
MUNDEN et al
•
OCULAR FINDINGS IN TURCOT SYNDROME
Fig 1. Top left, sagittal section magnetic resonance image demonstrates large, well-delineated, enhancing cerebellar tumor. Fig 2. Top right, computed tomography shows an enhancing posterior fossa mass centered over the cerebellar vermis with compression of the fourth ventrical. Partial calcification is evident within the mass. Fig 3. Second row left, photomicrograph shows neoplastic medulloblastoma cells with oval, dark-staining nuclei. Individual cell necrosis is prominent and mitotic figures are seen (hematoxylineosin; original magnification, X100). Fig 4. Second row right, endoscopic photograph of multiple colonic polyps. Fig 5. Third row left, endoscopic photograph of large polyps in descending colon at 40 cm. Fig 6. Third row right, photomicrograph of duodenal polyp biopsy showing a tubular adenoma without evidence of malignant transformation (hematoxylineosin, original magnification, X I00). Fig 7. Fourth row left, posterior retina showing triangular patch of CHRPE with surrounding hypopigmentation. Fig 8. Fourth row right, hypopigmented CHRPE lesion in the macula of the left eye. Fig 9. Bottom, mid periphery of retina showing small, oval patch of CHRPE and adjacent "comet-tail" hypopigmented lesion.
113
OPHTHALMOLOGY
•
JANUARY 1991
•
VOLUME 98
•
NUMBER 1
Table 1. Clinical Characteristics and Ocular Findings in the Inherited Gastrointestinal Polyposis Syndromes Gastrointestinal Lesions
Extraintestinal Lesions
Ocular Findings
Predisposition to Cancer
Adenomatous Polyposis Syndromes Familial adenomatous polyposis (AD)
Multiple (> 100) gastrointestinal polyps mainly in colon and rectum
None
CHRPE
Colon adenocarcinoma in all untreated patients2
Gardner syndrome (AD)
Same as familial adenomatous polyposis
Osteomas of the skull and mandible, epidermoid and dentigerous cysts, lipomas, fibromas, and desmoid tumors
CHRPE
Colon adenocarcinoma in all untreated patients, other cancers also reported (e.g., thyroid, liver, brain)2.5
Turcot's syndrome (considered AD by most authors, AR by otherst4,6
Same as familial adenomatous polyposis
Neuroepithelial brain tumors (medulloblastoma, glioblastoma)
CHRPE, neuroophthalmic signs of intracranial tumor
Colon adenocarcinoma, ileal reticulum cell sarcoma, and thyroid papillary carcinoma have been reported in association .15,18
Hamartomatous PolYPOSis Syndromes Peutz-Jeghers syndrome (AD)
Multiple (few to hundreds) gastrointestinal polyps, most frequently in small bowel
Melanin spots on lips, buccal mucosa, and digits. Hamartomas of other mucosal surfaces (nose, esophagus, bronchus)
Pigmentation of lids and conjunctiva
GI tract and other cancers in up to 48% of cases 2
Familial juvenile polyposis (AD)
Multiple gastrointestinal polyps, most frequently in colon and rectum
None
None
Probable, but magnitude of risk unknown 2
AD
=
autosomal dominant; CHRPE
=
congenital hypertrophy of the retinal pigment epithelium; AR
tumors, some individuals may not survive to the development of polyposis or any of the extracolonic manifestations of these inherited conditions. Consequently, all individuals with these central nervous system malignancies and any history suggestive of familial adenomatous polyposis should have a complete ophthalmic examination.
REFERENCES 1. Turcot J, Despres J-P, St. Pierre F. Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases. Dis Colon Rectum 1959; 2:465-8. 2. Haggitt RC, Reid BJ. Hereditary gastrOintestinal polyposis syndromes. Am J Surg Patho11986; 10:871-87. 3. Itoh H, Ohsato K, Yao T, et al. Turcot's syndrome and its mode of inheritance. Gut 1979; 20:414-9. 4. Romania A, lakov IN, McGannon E, et al. Congenital hypertrophy of the retinal pigment epithelium in familial adenomatous polyposis. Ophthalmology 1989; 96:879-84. 5. Smith WG, Kem BB. The nature of the mutation in familial multiple polyposis: papillary carcinoma of the thyroid, brain tumors, and familial multiple polyposis. Dis Colon Rectum 1973; 16:264-71. 6. Jarvis L, Bathurst N, Mohan D, Beckly D. Turcot's syndrome: a review. Dis Colon Rectum 1988; 31:907-14. 7. Traboulsi EI, Maumenee IH, Krush AJ, et al. Pigmented ocular fundus lesions in the inherited gastrointestinal polyposis syndromes and in hereditary non polyposis colorectal cancer. Ophthalmology 1988; 95: 964-9.
114
=
autosomal recessive.
8. Berk T, Cohen l, McLeod RS, Parker JA. Congenital hypertrophy of the retinal pigment epithelium as a marker for familial adenomatous polyposiS. Dis Colon Rectum. 1988; 31 :253-7. 9. Diaz-Llopis M, Menezo JL. Congenital hypertrophy of the retinal pigment epithelium in familial adenomatous polyposiS. Arch Ophthalmol 1988; 106:412-3. 10. Lewis RA, Crowder WE, Eierman LA, et al. The Gardner syndrome: significance of ocular features. Ophthalmology 1984; 91 :916-25. 11. Blair NP, Trempe CL. Hypertrophy of the retinal pigment epithelium associated with Gardner's syndrome. Am J Ophthalmol 1980; 90: 661-7. 12. Traboulsi EI, Krush AJ, Gardner EJ, et al. Prevalence and importance of pigmented ocular fundus lesions in Gardner's syndrome. N Engl J Med 1987; 316:661-7. 13. Traboulsi EI, Maumenee IH, Krush AJ, et al. Congenital hypertrophy of the retinal pigment epithelium predicts colorectal polYPOSis in Gardner's syndrome. Arch Ophthalmol1990; 108:525-6. 14. Baughman FA, List CF, Williams JR, et al. The glioma· polyposis syndrome. N Engl J Med 1969; 281:1345-6. 15. Jamjoom lAB, Sadiq S, Motti AB, et al. Turcot syndrome: report of a case and review of the literature. Int Surg 1989; 74:45-50. 16. Rothman D, Su CP, Kendall AB. Dilemma in a case of Turcot's (gliomapolyposis) syndrome: report of a case. Dis Colon Rectum 1975; 18: 514-5. 17. Chowdhary UM, Boehme DH, AI-Jishi M. Turcot syndrome (glioma polyposis). Case report. J Neurosurg 1985; 63:804-7. 18. Schroder S, Moehrs D, von Weltzien J, et al. The Turcot syndrome: report of an additional case and review of the literature. Dis Colon Rectum 1983; 26:533-8.
