Journal of Pediatric Ophthalmology and Strabismus

Short Subjects 

Retinoblastoma in a Patient With Lowe's Syndrome

Marta Zelter, MD; Marcela Gonorazky, MD; J Oscar Croxatto, MD; Juan P Wasserman, MD; Claudia Arberas, MD; Silvia Rothfeld, MD; Ma del Carmen Fernández, MD; Ana Tello, MD; Roxana Bonggi, MD

Abstract

INTRODUCTION

Retinoblastoma is the most common intraocular tumor of childhood.1 Approximately 90% of retinoblastoma present in a classic pattern of leukokoria and strabismus at an average age of 18 months.2 Unusual manifestations such as pseudohypopyon, glaucoma, cellulitis, and hyphema may delay the diagnosis and misdirect therapy.

Most children with retinoblastoma have a normal phenotype and do not have any other ocular and systemic abnormalities. The association of retinoblastoma and congenital cataracts is extremely rare, with only two reports in the literature.3,4

Oculocerebrorenal or Lowe's syndrome is an X1 inked disorder characterized by defective renal tubular reabsorption, aminoaciduria, hydrophdialmos, maladaptive behavior, hypotonia, and prominent forehead.5 Ocular findings include bilateral congenital cataracts, corneal keloids, hypoplasia of the iris, and glaucoma. Affected males have bilateral cataracts at birth and develop renal dysfunction in the first year of life. Female carriers are identified by the presence of typical punctate and plaque-like cataracts.6,7 Molecular linkage, genetic analysis, and study of the YAC chromosomes mapped the OCRL gene to die Xq24-q26 region.8 The coded OCRLl protein is a lipid phosphatase located in the Golgi complex that controls cellular levels of phospharidylinositol 4, 5 bisphosphate.9

This article reports a child with bilateral cataracts and retinoblastoma in which the diagnosis of Lowe's syndrome was made. No previous reports regarding this association have been published.

CASE REPORT

A 2-year-old boy presented to the Ophthalmology Unit of die Hospital de Niños de Buenos Aires Ricardo Gutierrez in June 1 996 with a left orbital mass (Figure 1). His parents stated the mass suddenly appeared 2 days before presentation. Physical examination showed a complete cataract in the right eye that precluded fundus examination. The bleeding and necrotic orbital mass entirely filled the lid aperture, apparendy replacing the eye. The most likely diagnosis was massive retinoblastoma with extraocular extension, and a fine-needle aspiration biopsy was performed. Cytopathologic examination revealed numerous viable and necrotic small atypical mononuclear cells, consistent with retinoblastoma.

Review of the hospital records revealed the patient had been examined at the age of 2 months for congenital, bilateral, dense cataracts and roving eyes. The results of A- and B-scan ultrasonography had been normal in both eyes. Examination under general anesthesia had not been performed because of the patient's poor clinical condition, which included hypotonia, dehydration, and severe mental retardation. Review of the neurology charts revealed die presence of a noncalcified small mass in the left eye noted in a computed tomography (CT) scan of the brain (Figure 2). Unfortunately, die results of that study had not been referred to the ophdialmologist. After recovery of his clinical condition, the parents did not return for periodic examination until the current presentation.

Enucleation of the mass including die distorted eye was performed. Histopathologic examination showed an undifferentiated retinoblastoma that filled the eye and extended to die anterior orbit and posterior with invasion of die optic nerve up to the level of surgical excision (Figure 3). A complete work-up did not reveal evidence of metastatic disease. The patient received additional treatment with radiotherapy to die left orbit and chemotherapy, according to protocols for histopathologic staging.

The pediatricians suspected die diagnosis of Lowe syndrome based on die presence of bilateral congenital cataracts, severe mental retardation, hypotonia, dehydration, aminoaciduria, and dénutrition.

Examination of his mother showed multiple punctate opacities at the lens consistent with a female carrier of the disease. A standard cytogenetic evaluation was performed on the patient's blood and tumor and showed die child to have a normal 46 XY karyotype. High-resolution chromosomal analysis revealed a deletion of die ql4 band on chromosome 13.

One year after enucleation, there was no evidence of recurrence…

INTRODUCTION

Retinoblastoma is the most common intraocular tumor of childhood.1 Approximately 90% of retinoblastoma present in a classic pattern of leukokoria and strabismus at an average age of 18 months.2 Unusual manifestations such as pseudohypopyon, glaucoma, cellulitis, and hyphema may delay the diagnosis and misdirect therapy.

Most children with retinoblastoma have a normal phenotype and do not have any other ocular and systemic abnormalities. The association of retinoblastoma and congenital cataracts is extremely rare, with only two reports in the literature.3,4

Oculocerebrorenal or Lowe's syndrome is an X1 inked disorder characterized by defective renal tubular reabsorption, aminoaciduria, hydrophdialmos, maladaptive behavior, hypotonia, and prominent forehead.5 Ocular findings include bilateral congenital cataracts, corneal keloids, hypoplasia of the iris, and glaucoma. Affected males have bilateral cataracts at birth and develop renal dysfunction in the first year of life. Female carriers are identified by the presence of typical punctate and plaque-like cataracts.6,7 Molecular linkage, genetic analysis, and study of the YAC chromosomes mapped the OCRL gene to die Xq24-q26 region.8 The coded OCRLl protein is a lipid phosphatase located in the Golgi complex that controls cellular levels of phospharidylinositol 4, 5 bisphosphate.9

This article reports a child with bilateral cataracts and retinoblastoma in which the diagnosis of Lowe's syndrome was made. No previous reports regarding this association have been published.

CASE REPORT

A 2-year-old boy presented to the Ophthalmology Unit of die Hospital de Niños de Buenos Aires Ricardo Gutierrez in June 1 996 with a left orbital mass (Figure 1). His parents stated the mass suddenly appeared 2 days before presentation. Physical examination showed a complete cataract in the right eye that precluded fundus examination. The bleeding and necrotic orbital mass entirely filled the lid aperture, apparendy replacing the eye. The most likely diagnosis was massive retinoblastoma with extraocular extension, and a fine-needle aspiration biopsy was performed. Cytopathologic examination revealed numerous viable and necrotic small atypical mononuclear cells, consistent with retinoblastoma.

Review of the hospital records revealed the patient had been examined at the age of 2 months for congenital, bilateral, dense cataracts and roving eyes. The results of A- and B-scan ultrasonography had been normal in both eyes. Examination under general anesthesia had not been performed because of the patient's poor clinical condition, which included hypotonia, dehydration, and severe mental retardation. Review of the neurology charts revealed die presence of a noncalcified small mass in the left eye noted in a computed tomography (CT) scan of the brain (Figure 2). Unfortunately, die results of that study had not been referred to the ophdialmologist. After recovery of his clinical condition, the parents did not return for periodic examination until the current presentation.

Figure 1: Left orbital mass at presentation.

Figure 1: Left orbital mass at presentation.

Figure 2: CT scan at age 2 months showed a noncalcified intraocular mass.

Figure 2: CT scan at age 2 months showed a noncalcified intraocular mass.

Figure 3: The enucleated eye was filled by a massive undifferentiated retinoblastoma with rupture of the globe and invasion of the conjunctiva and orbit (hematoxylin and eosin, original magnification X25).

Figure 3: The enucleated eye was filled by a massive undifferentiated retinoblastoma with rupture of the globe and invasion of the conjunctiva and orbit (hematoxylin and eosin, original magnification X25).

Enucleation of the mass including die distorted eye was performed. Histopathologic examination showed an undifferentiated retinoblastoma that filled the eye and extended to die anterior orbit and posterior with invasion of die optic nerve up to the level of surgical excision (Figure 3). A complete work-up did not reveal evidence of metastatic disease. The patient received additional treatment with radiotherapy to die left orbit and chemotherapy, according to protocols for histopathologic staging.

The pediatricians suspected die diagnosis of Lowe syndrome based on die presence of bilateral congenital cataracts, severe mental retardation, hypotonia, dehydration, aminoaciduria, and dénutrition.

Examination of his mother showed multiple punctate opacities at the lens consistent with a female carrier of the disease. A standard cytogenetic evaluation was performed on the patient's blood and tumor and showed die child to have a normal 46 XY karyotype. High-resolution chromosomal analysis revealed a deletion of die ql4 band on chromosome 13.

One year after enucleation, there was no evidence of recurrence of the rumor, but severe decompensation of his metabolic condition.

DISCUSSION

The clinical manifestations of a retinoblastoma vary with the stage of the disease at first examination and could be easily overlooked in the early stages of development.10 Our patient had a very small mass at an early age that was not visualized because of the cataract, nor was it noted on A- and B-scan ultrasonographic examination. However, a CT scan of the brain did show a noncalcified small intraocular mass that was overlooked. Eyes with retinoblastoma are of normal and equal size to the opposite eye, and the lens is usually clear. Even in cases of advanced retinoblastoma with apposition of thie tumor to the posterior lens capsule, a secondary cataract almost never develops.

The case reported here presented the unusual concurrence of congenital cataract and retinoblastoma. Friendly and Parks3 described an affected boy who inherited both diseases, one from each parent. Brown et al4 showed an association between retinoblastoma and anterior polar cataracts. Our patient did not have a family history of either retinoblastoma or congenital cataracts, but his mother had a typical punctate cataract found in female carriers of Lowe's syndrome. The presence of signs and symptoms of defective renal tubular reabsorption, cataract, hypotony, and mental retardation supported the clinical diagnosis.

This is the first report describing die development of a sporadic unilateral retinoblastoma in a patient with Lowe's syndrome. The retinoblastoma gene and die oculocerebrorenal Lowe gene are located in two unrelated loci without any expected genetic linkage between them.

REFERENCES

1. Med 1 . Schweisgutli O. Tumeurs solides de l'enfant. Flan Sci. 1976:220-225.

2. Zelter M, Gonzalez G, Schwartz L. A prospective study on die treatment of retinoblastoma in 72 patients. Cancer. 1991;68:1685-1690.

3. Friendly D, Parks M. Concurrence of hereditary congenital cataracts and hereditary retinoblastoma- Arch Ophthalmol 1970;84:525-527.

4. Brown G, Shields JA, Oglesby RB. Anterior polar cataracts associated with retinoblastoma. Am J Ophthalmol. 1979;87:276-277.

5. Lowe C, Terrey M, MacLachlan F. Organic-aciduria, decreased renal ammonia production, hydrophthalmos and mental retardation. J Dis Child. 1952;83:164-184.

6. Martin V, Carson N. Inborn metabolic disorders with associated ocular lesions in Northern Ireland. Trans UK Ophthal Soc. 1967;87:847-870.

7. Cibis G, Waeltermann J, Whitcraft C. Lenticular opacities in carriers of Lowe's syndrome. Ophthalmology 1986;93:1041-1045.

8. Silver D, Lewis R, Nussbaum R. Mapping die Lowe oculo-cerebro-renal syndrome to Xq24-q26 by use of restriction fragment length polymorphisms. J Clin Invest. 1987;79:282-285.

9. Zhang X, Jefferson A, Auethavekiat V, Majerus P. The protein deficient in Lowe syndrome is a phosphatidylinositoI-4,5-bisphosphatasc. Proc Nat Acad Sci USA. 1995;92:4853-4856.

10. Shields J, Shields C. Diagnosis approaches to retinoblastoma. In: Shields J, ed. lntraocular Tumors. Philadelphia, Pa: WB Saunders; 1992:363-377.

10.3928/0191-3913-20000301-12

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