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Retinal Hamartoma in Oral-Facial-Digital Syndrome

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Retinal Hamartoma in Oral-Facial-Digital Syndrome CLINICOPATHOLOGIC REPORT Retinal Hamartoma in Oral-Facial-Digital Syndrome Patricia S. Tsai, BS; Joan M. O’Brien, MD nly recently have intraocular findings been described in oral-facial-digital syndrome (OFDS), including 5 cases of chorioretinal colobomas and 1 case of optic nerve colo- boma. We report a case of a new ocular anomaly associated with this syndrome: a retinal hamartoma in a male infant with OFDS. The patient had bilateral retinal masses Othat were suspicious for retinoblastoma because of a family history of retinoblastoma. Physical ex- amination and imaging studies of the retinal masses could not differentiate between retinoblas- toma, hamartoma, or persistent hyperplastic primary vitreous. Subsequent pathologic study of an enucleated globe was diagnostic of a retinal hamartoma. This case further illustrates the hetero- geneity of ocular anomalies in OFDS and underscores the importance of a complete ophthalmo- logic evaluation in patients with this syndrome. Arch Ophthalmol. 1999;117:963-965 Oral-facial-digital syndrome (OFDS) de- mother with a history of unilateral reti- scribes a group of syndromes character- noblastoma who was otherwise pheno- ized by congenital anomalies of the oral typically normal. Both the parents and the cavity (cleft palate, tongue hamartomas, paternal grandparents were first cousins. bifid tongue, multiple hyperplastic Pregnancy was without complication, and frenula), face (hypoplastic nasal carti- the infant was delivered at 39 weeks’ ges- lage), and digits (syndactyly, polydac- tation. The infant was initially mildly hy- tyly, brachydactyly, clinodactyly). Oph- potonic but quickly improved. Physical thalmologic findings that have been examination and subsequent genetic evalu- reported in OFDS include hypertelorism, ation revealed multiple congenital anoma- strabismus, and seesaw winking.1 Only re- lies consistent with OFDS, including mul- cently have intraocular findings been re- tiple tongue hamartomas, corrugated ported, including 5 cases of chorioretinal gingiva, short flat bridge of nose, and bi- colobomas and 1 case of optic nerve colo- lateral polydactyly of the hands and feet boma.2-6 However, ocular findings in most (Figure 1, Figure 2, and Figure 3). cases of OFDS have not been well docu- Other considerations included in the dif- mented, and ocular manifestations of ferential diagnosis were retinoblastoma, OFDS are still not well described in the persistent hyperplastic primary vitreous, ophthalmologic literature. Here we re- and Norrie’s disease. port a case of an ocular finding not pre- Ophthalmologic examination was viously described in OFDS, a case of an in- performed at the University of Califor- fant with OFDS and a family history of nia, San Francisco, when the infant was retinoblastoma who was originally seen 10 days old. The infant exhibited hyper- with bilateral retinal masses. telorism and bilateral blepharophimosis. It could not be determined whether he had REPORT OF A CASE any useful vision. The iris was dysmor- phic with irregular borders in both eyes. A full-term male infant was referred to us Also in both eyes was a retinal yellow- because of suspected bilateral retinoblas- white mass with overlying hemorrhage. No toma. This was the first pregnancy of a evidence of normal retinal vasculature was associated with the masses. Ultrasonog- From the Department of Ophthalmology, University of California, San Francisco. raphy demonstrated a solid mass without ARCH OPHTHALMOL / VOL 117, JULY 1999 963 ©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 intrinsic calcification. A computed or calcify, enucleation of the worse Corneal diameters were also in- tomographic scan of the orbits eye would be performed for treat- creased bilaterally: 11.5 mm verti- showed bilateral intraocular masses ment and diagnosis. cally and 11.0 mm horizontally in without the calcifications typical of At 2 months of age, a com- the right eye, and 9.0 mm vertically retinoblastoma. The scan also re- puted tomographic scan of the or- and 9.0 mm horizontally in the left vealed small optic nerves bilater- bit demonstrated no further growth eye. Medical treatment of the glau- ally. It could not be determined of the masses but did indicate new coma was instituted. Enucleation of whether the masses represented reti- calcification in the right eye, con- the right eye with placement of a noblastoma, hamartomas, or some sistent with the diagnosis of retino- prosthesis was performed without variant of persistent hyperplastic pri- blastoma. At the time of enucle- complication. mary vitreous. It was the recommen- ation, the infant exhibited no fixation Pathologic examination of the dation of the Pediatric Tumor Board, or following behavior. Ophthalmic enucleated right eye revealed a to- University of California, San Fran- examination revealed a completely tal retinal detachment in a funnel cisco, to maintain close observa- flat anterior chamber in the right eye configuration with eosinophilic exu- tion with eye examinations per- and a formed chamber with some date filling the subretinal space. The formed under anesthesia every few synechiae in the left eye. Pneumo- retinal layers were disorganized with weeks. If the retinal masses did not tonometry showed elevated pres- areas of dysplasia (Figure 4 and change, observation would con- sures bilaterally, with 28 to 29 Figure 5). These findings were con- tinue; if the masses began to grow mm Hg OD and 24 to 25 mm Hg OS. sistent with a retinal hamartoma. In Figure 1. Patient’s lips and tongue with multiple hamartomas at the distal end of the tongue. Figure 4. Dysplastic retina with disorganization of normal retinal layers and no evidence of neoplasia (hematoxylin-eosin, original magnification 340). Figure 2. Evidence of polydactyly. The patient has 6 fingers on each hand. Figure 3. Patient’s left foot with 6 toes (the right foot also has 6 toes). Figure 5. Higher-power view of dysplastic retina (hematoxylin-eosin, original magnification 3100). ARCH OPHTHALMOL / VOL 117, JULY 1999 964 ©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 IX has been the only type associ- To our knowledge, this article ated with intraocular findings. How- reports the first case of OFDS asso- ever, it is unclear whether com- ciated with retinal hamartoma. Be- plete ophthalmologic examinations cause of many prior reported cases were performed on the early re- of ocular anomalies associated with ported cases of OFDS; intraocular OFDS, it is likely that our patient’s anomalies therefore cannot be ex- ocular anomalies are related to his cluded in other types of OFDS. Our OFDS rather than being just coin- patient has findings most consis- cidental findings. This case further tent with OFDS type IX. To date, illustrates the heterogeneity of ocu- only 6 prior cases of OFDS type IX lar anomalies in OFDS and under- have been reported, including 5 scores the importance of a com- Figure 6. Fundus photograph of posterior pole cases of chorioretinal colobomas and plete ophthalmologic evaluation in in the left eye, taken through the central 1 case of optic nerve coloboma. To patients with this syndrome. cataractous lens, demonstrates a central our knowledge, retinal masses, such yellow-white mass possibly consistent with persistent hypoplastic primary vitreous. as the ones in our patient, have never Accepted for publication December 26, been reported in OFDS. 1998. Because of the lack of prece- We are grateful to Sharon addition, pathologic studies also dent, it was uncertain initially if our Wheeler for her editorial comments. demonstrated an iris in apposition patient’s bilateral retinal masses were Reprints: Joan M. O’Brien, MD, to the corneal endothelium produc- hamartomas and if this type of ham- Department of Ophthalmology, Uni- ing apposition angle closure. The op- artoma was even consistent with versity of California, San Francisco, tic nerve was atrophic with no evi- OFDS. Because our patient’s mother 10 Kirkham St, Box 0730, San Fran- dence of neoplastic invasion. No had a history of unilateral retino- cisco, CA 94143-0730. calcification or retinoblastoma was blastoma, the possibility that the reti- seen. nal masses were retinoblastoma was REFERENCES Cytogenetic testing revealed also very likely. Patients with uni- normal chromosomes by G-band lateral retinoblastoma have a re- analysis. ported 15% risk of germline muta- 1. Toriello HV. Heterogeneity and variability in the oral-facial-digital syndromes. Am J Med Genet. tion. Ophthalmologic examination 1988;4(suppl):149-159. COMMENT and imaging studies also raised the 2. Gurrieri F, Sammito V, Ricci B, Iossa M, Bellussi possibility of persistent hyperplas- A, Neri G. Possible new type of oral-facial-digital Oral-facial-digital syndrome was first tic primary vitreous and Norrie’s dis- syndrome with retinal abnormalities: OFDS type described by Papillon-League and ease. Because the right retinal mass (VIII). Am J Med Genet. 1992;42:789-792. 3. Jamieson R, Collins F. Oral-facial-digital syn- Psaume in 1954, and since then, up later developed some calcification, drome and retinal abnormalities with autosomal to 9 distinct types of OFDS have which was most consistent with a recessive inheritance. Am J Med Genet. 1993;47: been described. Ocular findings that diagnosis of retinoblastoma, enucle- 304-306. have been described include hyper- ation of the right eye was per- 4. Stevens JL, Marsh JL. Ocular anomalies in the oral- telorism in types I, II, III, IV, and VI; formed. Only after pathologic eval- facial-digital syndrome. J Pediatr Ophthalmol Stra- bismus. 1994;31:397-398. strabismus in I, II, and IV; and see- uation of the globe was the final 5. Nevin NC, Silvestri J, Kernohan DC, Hutchinson 1 saw winking in type IV. Recently, diagnosis of hamartoma deter- WM. Oral-facial-digital syndrome with retinal ab- a new type (originally described as mined. However, the appearance of normalities, OFDS type IX: a further case report. type VIII, but reclassified as type IX) the left eye (Figure 6) and subse- Am J Med Genet.
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