Glaucoma in Oculo-Dento-Osseous Dysplasia

Elias I. Traboulsi, M.D., and Marshall M. Parks, M.D.

Two patients with oculo-dento-osseous dys­plasia developed glaucoma in infancy or earlychildhood. Aggressive surgical managementresulted in the preservation of vision in bothpatients in at least one eye. A review of pub­lished reports disclosed that glaucoma inoculo-dento-osseous dysplasia develops atdifferent ages and is possibly secondary to avariety of mechanisms. Glaucoma is the maincause of visual loss in this syndrome, forwhich patients otherwise have a good progno­sis for life and intellect. Early screening forglaucoma in oculo-dento-osseous dysplasia ismandatory, especially when there are symp­toms that suggest high intraocular pressure.

OCULO-DENTO-OSSEOUS DYSPLASIA is a malfor­mation syndrome that involves the hair, face,eyes, teeth, and bones.':' The mode of inheri­tance is generally autosomal dominant, but arecessive variety probably exists."! Patientswith oculo-dento-osseous dysplasia have acharacteristic physiognomy that features a longface with scarce eyebrows, narrow and shortpalpebral fissures, microcornea or microphthal­mia, and a small nose with hypoplastic alaenasae and a prominent columella. The dentalenamel is dysplastic, and microdontia or hypo­dontia may be present.

Skeletal abnormalities are most prominent inthe distal parts of the extremities with carnpto­dactyly or syndactyly of the ulnar two or threedigits; the toes are short and frequently lacksecond metatarsals. Other skeletal abnormali­ties include calvarial hyperostosis, a heavymandible with an obtuse angle between itsbody and rami, plump clavicles, thickened ribs,

Accepted for publication Dec. 21, 1989.From the Department of Ophthalmology, Children's

National Medical Center (Dr. Traboulsi), and GeorgeWashington University School of Medicine (Dr. Parks),Washington, D.C.

Reprint requests to Elias I. Traboulsi. M.D., Depart­ment of Ophthalmology, Children's National MedicalCenter, 111 Michigan Ave. N.W., Washington, D.C.20010.

and poorly tubulated long bones. Generalizedhair abnormalities are manifested by hypotri­chosis, trichorrhexis, and dry lusterless hairincluding eyebrows and eyelashes. Less com­mon abnormalities include cleft lip or palate orboth, conductive hearing loss, hip dislocation,and osteopetrosis. Intellect is generally normal.

Eyelid abnormalities in oculo-dento-osseousdysplasia include telecanthus and epicanthalfolds in most patients. Hypotelorism is presentin 40% of patients." Convergent strabismus is afrequent finding. The globe may be involved asa whole with microphthalmos and anterior seg­ment dysgenesis, or the abnormalities may berestricted to dysgenesis of the anterior segmentwith normal ocular size. Axial length measure­ments may be normal or below normal." Ante­rior segment dysgenesis may be more severein the rarer presumed recessive form of oc­ulo-dento-osseous dysplasia.' Remnants of thepupillary membrane are frequently present.Cataracts have been reported in two cases.v"Posterior segment abnormalities have includedremnants of the hyaloid system':" and increasednumbers of retinal vessels at the optic disk."

Different types of glaucoma have been report­ed in ten patients with oculo-dento-osseousdysplasia. 1,8,IO.14 Although glaucoma was postu­lated to be present in another two cases of oc­ulo-dento-osseous dysplasia," review of thesereports showed that in one instance the patientprobably had Rieger's syndrome," and in theother case the patient had a previously un­described syndrome of glaucoma and probableectodermal dysplasia, but not oculo-dento­osseous dysplasia."

We treated two patients with oculo-dento­osseous dysplasia and infantile or developmen­tal glaucoma.

Case Reports

Case 1This patient's glaucoma was first diagnosed

in her right eye in 1969 at age 5th years when

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Vol. 109, No.3 Glaucoma in Oculo-Dento-Osseous Dysplasia 311

she had an intraocular pressure of 40 mm Hg, acup/disk ratio of 0.8, and visual acuity of R.E.:20/300. She did not respond to medical treat­ment and underwent a filtering procedure inthe right eye; the filtering bleb failed over a fewmonths. Glaucoma was found in her left eye atage 7 years when she was referred to one of us(M.M.P.) for further treatment. Hallerman­Streiff syndrome had been diagnosed.

On examination, we found typical facial fea­tures of oculo-dento-osseous dysplasia withhypotrichosis of the scalp hair and eyebrows,small eyes, and hypoplastic alae nasae. She alsohad syndactyly and clinodactyly of her fourthand fifth digits in both hands. Intraocular pres­sure was R.E.: 38 mm Hg and 1.E.: 33 mm Hg.The right cornea was larger than the left, andthere were large breaks in Descemet's mem­brane in both eyes; both corneas, however,were less than 10 mm in size, with mild sclerali­zation superiorly and inferiorly. There was afailed filtering bleb superiorly in her right eye,and the patient had undergone a peripheraliridectomy. Posterior synechiae were also pres­ent in the right eye, in which there were alsoposterior cortical lens opacities. In the left eye,extensive remnants of the pupillary membranewere present, which bridged the anterior lenssurface and the iris collarette in the superiorhalf of the pupil. A retinoscopy disclosed-12.00 diopters in the right eye and -5.00diopters in the left eye. A goniotomy was per­formed in the left eye but was difficult becauseof poor visualization, and it did not result indecrease in the intraocular pressure. A filteringprocedure was subsequently performed on theleft eye with good control of the intraocularpressure. With the administration of pilocar­pine and later of timolol maleate, the intraocu­lar pressure in the left eye remained adequatelycontrolled over the next several years with avisual acuity of 20/30. The drops were subse­quently discontinued, and the intraocular pres­sure in the left eye continued to be in the 12- to14-mm Hg range until the patient's last visit in1988. The right eye was enucleated in 1984because of absolute glaucoma.

Case 2This patient was first examined at the age of 4

months because her eyes appeared abnormaland crossed since birth. The prenatal, perinatal,and postnatal histories were unremarkable ex­cept for difficulties in breast-feeding. There wasno apparent weakness of the facial muscles.Facial appearance was typical of oculo-dento-

Figure (Traboulsi and Parks). Patient 2 at 8 monthsof age. Note typical facial features of oculo-dento­osseous dysplasia: narrow eyelid fissures, telecan­thus, small nose with prominent columella and re­ceding alae nasae, and fine hair.

osseous dysplasia (Figure), although a diagno­sis of Moebius syndrome had been considered.She had syndactyly of the third, fourth, andfifth fingers in each hand. Ocular examinationdisclosed central, steady, and maintained fixa­tion in both eyes and an esotropia of 45 prismdiopters. There was a myopia of -5.00 dioptersin each eye. The cornea measured 8.5 mm inboth eyes, and remnants of the pupillary mem­brane were present in both eyes. Both lenseswere clear. Indirect ophthalmoscopy disclosedmoderately severe tilting of the left optic disk.

At age 6 months, the patient underwent bilat­eral medial rectus recession by 6 mm, whichresulted in an overcorrection to 20 prism diop­ters of exotropia. Her myopia progressed to- 8.00 diopters in both eyes over three months,and photophobia became apparent. Examina­tion under anesthesia at age 9 months showedhorizontal breaks in Descemet's membrane inboth eyes and increased intraocular pressure(R.E.: 22 mm Hg and 1.E.: 29 mm Hg). Thegonioscopic appearance of the angle was simi­lar to that in primary infantile glaucoma; theiris was slightly dysplastic with mild hypoplas­ia inside the collarettes. The cup/ disk ratio was0.5 in the right eye and 0.4 in the left eye.Goniotomies were performed on both eyes fourweeks apart with intraocular pressure reduc-

312 AMERICAN JOURNAL OF OPHTHALMOLOGY March, 1990

tion to 20 mm Hg in each eye. Timolol maleate0.5% was started in both eyes. The intraocularpressure increased to 30 mm Hg in the left eye,and a trabeculectomy was performed at age 1%years with subsequent control of intraocularpressure in that eye.

The patient's myopia continued to progress(-10.50 diopters in the right eye and -13.50diopters in the left eye) despite good controlof intraocular pressure, which was checkedunder anesthesia on multiple occasions. At age2% years, the patient underwent bilateral later­al rectus muscle recession for her consecutiveexotropia. She remained orthophoric for sever­al weeks and later varied between moderateesotropia and moderate exotropia on differentexaminations. She developed amblyopia of herleft, more myopic, eye and is currently receiv­ing occlusion therapy. Her visual acuity on herlast visit at age 5 years disclosed a visual acuityof R.E.: 20/60 and L.E.: 20/200, and an in­traocular pressure of 14 mm Hg in each eye,as measured by applanation tonometry. Hercup/disk ratio had regressed to 0.25 in eacheye.

Discussion

Glaucoma can develop in oculo-dento-osse­ous dysplasia at different ages and has a varietyof causes. In infancy, the pathogenesis appearsto be similar to that of isolated infantile glauco­ma, that is, failure of drainage of aqueoushumor because of trabeculodysgenesis.

Trabeculodysgenesis in oculo-dento-osseousdysplasia is probably a manifestation of theanterior segment dysgenesis present in most ofthese patients. The presence of horizontalbreaks in Descemet's membrane in both pa­tients described in this report suggests thattheir glaucoma began early in infancy. Infan­tile glaucoma in oculo-dento-osseous dysplasiawas previously reported in two patients.":"Anterior segment dysgenesis also predisposesthe patient to the development of glaucomain childhood or early adulthood, as is the casein patients with isolated Axenfeld's-Rieger'sspectrum of anomalies. The patients describedby Meyer-Schwikerath, Gruterch, and Weyers,'Weintraub, Baum, and Pashayan," and Dudg­eon and Chisholm" are in this second categoryof glaucoma in oculo-dento-osseous dysplasia.The third category includes patients with an

adult-onset, open-angle glaucoma, which waspresent in one affected member of the familydescribed by Dudgeon and Chisholm." Thisglaucoma may theoretically also be secondaryto anterior segment dysgenesis or it may repre­sent a case of chronic simple glaucoma, whichmay be more common in patients with oculo­den to-osseous dysplasia. The fourth group in­cludes patients with an angle-closure mecha­nism, which has been reported by Sugar" inone eye of one patient who had infantile glau­coma in the other eye. In that report, Sugarupdated the information on a patient he hadpreviously described" who also developed an­gle-closure glaucoma in midadulthood; a lensof normal size in a small globe with a crowdedanterior segment is known to predispose an eyeto the development of angle-closure glaucoma.

At least three other patients with oculo­dento-osseous dysplasia have been reported tobe blind from infancy or early childhood.v" Wesuspect that glaucoma may have been the causeof blindness in these patients.

Glaucoma is the most common cause of visualloss in patients with oculo-dento-osseous dys­plasia. Regular intraocular pressure measure­ments should be initiated as soon as possibleafter diagnosis, especially in the presence ofsymptoms or signs suggesting glaucoma, suchas tearing, photophobia, and hazy or enlargedcorneas. The management of glaucoma in thesepatients may be difficult, and initial operationsmay fail; aggressive management, however, ismandatory and may result in good long-termcontrol of intraocular pressure and the preser­vation of vision.

References

1. Meyer-Schwikerath, G., Gruterch, E., andWeyers, H.: Mikrophthalmus-syndrome. Klin.Monatsbl. Augenheilkd. 131:18, 1957.

2. Gorlin, R. J., Meskin, L. H., and Geme, J. W.:Oculodentodigital dysplasia. J. Pediatr. 63:69, 1963.

3. Gillespie, F. D.: A hereditary syndrome. "Dys­plasia oculodentodigitalis." Arch. Ophthalmol.71:187, 1964.

4. Traboulsi, E. I., Faris, B. M., and DerKaloustian, V. M.: Persistent hyperplastic primaryvitreous and recessive oculo-dento-osseous dyspla­sia. Am. J. Med. Genet. 24:95, 1986.

5. International Nomenclature of ConstitutionalDiseases of Bone. Revision, May 1983. Ann. Radiol.(Paris) 26:457,1983.

Vol. 109, No.3 Glaucoma in Oculo-Dento-Osseous Dysplasia 313

6. Fara, M., and Gorlin, R. J.: The question ofhypertelorism in oculodentoosseous dysplasia. Am.J. Med. Genet. 10:101, 1981.

7. [udisch. G. F., Martin-Casals, A., Hanson, J. W.,and Olin, W. H.: Oculodentodigital dysplasia. Fournew reports and a literature review. Arch. Ophthal­mol. 97:878, 1979.

8. Beighton, P., Hamersma, H., and Raad, M.:Oculodentoosseous dysplasia. Heterogeneity or vari­able expression? Clin. Genet. 16:169, 1979.

9. Guttierez-Diaz, A., Alonso, M. J., and Borda,M.: Oculodentodigital dysplasia. OphthalmicPaediatr. Genet. 1:227,1982.

10. Dudgeon, J., and Chisholm, 1. A.: Oculo dentodigital dysplasia. Trans. Ophthalmol. Soc. U.K.94:203,1974.

11. Sugar, H. 5.: Oculodentodigital dysplasia syn­drome with angle-closure glaucoma. Am. J. Ophthal­mol. 86:36, 1978.

12. Sugar, H. 5., Thompson, J. P., and Davis, J. D.:The oculo-dento-digital dysplasia syndrome. Am. J.Ophthalmol. 61: 1448, 1966.

13. Kadrnka-Lovrencic, M., [urkovic, 5., Reiner­Banovac, Z., Najman, E., and Lovrencic, M.: Dyspla­sia oculodentodigitalis. Monatsschr. Kinderheilkd.121:595, 1973.

14. Weintraub, D. M., Baum, J. L., and Pashayan,H. M.: A family with oculodentodigital dysplasia.Cleft Palate J. 12:323, 1975.

15. Brailey, W. A.: Double microphthalmos withdefective development of iris, teeth, and anus. Glau­coma at an early age. Trans. Ophthalmol. Soc. U.K.10:139, 1890.

16. Holmes, L. B., and Walton, D. 5.: Hereditarymicrocornea, glaucoma and absent frontal sinuses. Afamily study. J. Pediatr 74:968,1969.

OPHTHALMIC MINIATURE

]adine nodded. It seemed like a perfect exit line to her, since she didn'tknow what he was talking about and didn't want to pursue his thoughts ifthey were anything like his eyes at this moment. Without melanin, theywere all reflection, like mirrors, chamber after chamber, corridor aftercorridor of mirrors, each one taking its shape from the other and giving itback as its own until the final effect was color where no color existed at all.

Toni Morrison, Tar BabyNew York, New American Library, Inc., 1983, p. 62