Correspondence and reprintrequests to:Maria FrassonRua Bernardo Guimarães1020, apto 602. Bairro Funcionários,CEP 30140-081Belo HorizonteMinas GeraisBrasilTel: 55 31 3262 0434Fax: 55 31 3248 9768E-mail: frasson@task.com.br

Abstract Oculodentodigital dysplasia (ODDD) is a rare inheriteddisorder affecting the development of the face, eyes, teeth, and limbs.The majority of cases of ODDD are inherited as an autosomal domi-nant condition. There are few reports of probable autosomal recessivetransmission. Affected patients exhibit a distinctive physiognomy witha narrow nose, hypoplastic alae nasi, and anteverted nostrils, bilateralmicrophthalmos, and microcornea. Sometimes iris anomalies and sec-ondary glaucoma are present. There are malformations of the distalextremities such as syndactyly. In addition, there are defects in thedental enamel with hypoplasia and yellow discoloration of the teeth.Less common features include hypotrichosis, intracranial calcifications,and conductive deafness secondary to recurrent otitis media. Wedescribe three brothers with ODDD.Their parents are first cousins andpresent no features of ODDD. These data are in favor of autosomalrecessive inheritance and suggest genetic heterogeneity for this entity.

Key words Oculodentodigital dysplasia; autosomal recessive; eyemanifestations.

Introduction Oculodentodigital dysplasia (ODDD) is a rare in-herited disorder affecting the development of the face, eyes, teeth,and limbs. Although the first case of ODDD was probably reported by Lohmann in 1920, this name was firstly suggested by Meyer-

Oculodentodigital dysplasia with autosomal recessive inheritance 227

Ophthalmic Genetics 1381-6810/04/US$ 22.00

Ophthalmic Genetics – 2004, Vol. 25No. 3, pp. 227–236© 2004 Taylor & Francis Ltd.

DOI: 10.1080/13816810490513424

Accepted 21 April 2004

Oculodentodigital dysplasia: study ofophthalmological and clinical

manifestations in three boys with probablyautosomal recessive inheritance

Maria Frasson1,2

Nassim Calixto1

Sebastião Cronemberger1

Regina Amélia Lopes Pessoa de Aguiar2

Letícia Lima Leão2

Marcos José Burle de Aguiar2

1Hospital São Geraldo, Department of Ophthalmology, FederalUniversity of Minas Gerais, Brasil.

2Clinical Genetic Service, Federal University of Minas Gerais, Brasil.

Case report

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Schwickerath et al. Gillespie presented brother and sister with bilateralmicrophthalmos, hypotrichosis, enamelogenesis imperfecta, and camp-todactlyly of the fifth fingers. Gorlin et al. have established the acronymODDD. After that, several articles reported other cases, the majoritysporadic and autosomal dominant forms (Table 2). Traboulsi et al.described a girl with ODDD and severe ocular affection, probably rep-resenting autosomal recessive transmission. In linkage studies, Gladwinet al. mapped the ODD locus at chromosome 6q22-q24. Recently,Paznekas et al. found mutations in the connexin 43 gene in 17 familieswith ODDD causing pleiotropic phenotype.

This article presents the findings of ODDD in three sons of a normalconsanguineous couple, suggesting autosomal recessive inheritance.Routine ophthalmologic examinations, echobiometry, hands and feetradiograms, computed tomography (CT)-scan of the head, and karyo-types were performed.

Case report In 1994, we examinated a newborn boy, son of youngand first-cousin parents. This child had a small nose with antevertednostrils, bilateral cutaneous syndactyly of the second and third toes, car-diomyopathy, and a normal karyotype. At two years of age he died ofpneumonia. In 1995, his brother was born, also with features of ODDDconsisting of characteristic facies as described before, hypotrichosis,and intracranial calcifications. Radiograms revealed bilateral absenceof the middle phalanx of the second through fifth toes. During hisgrowth we observed severe tooth enamel defects requiring partialdental prosthesis after dental extraction. The patient showed a milddegree of mental retardation. His karyotype was normal. In 2002,another son was born with similar dysmorphisms comprising bilateralcutaneous syndactyly of the five toes, with absence of the middlephalanx of the second through fifth toes. Intracranial calcifications werealso present on his CT scan of the head in the region of the basalganglia. His karyotype was normal. Radiograms of the two youngerbrothers showed broadening of the tubular bones.

The mother is 27 years of age and the father is 30. Their general physical and ophthalmologic examinations were normal. In addition,no abnormalities were found in their radiograms. No other similar caseswere found in the family.

228 M. Frasson et al.

Oldest boy Second boy Youngest boy(exam at 3months of age)

Corrected visual acuity — <20/400 —IOP by applanation 6 6 4 (RE)

(mmHg) (OU) (OU) 5 (LE)Corneal diameter 6.0 ¥ 6.0 6.0 ¥ 6.0 7.25 ¥ 6.50 (RE)

(H ¥ V; mm) (OU) (OU) 7.0 ¥ 6.0 (LE)Anterior chamber depth 2.30 2.07 (RE) 2.68 (RE)

(mm) (OU) 1.88 (LE) 2.41 (LE)Axial length 17.51 (RE) 18.62 (RE) 18.61

(mm) 16.73 (LE) 18.85 (LE) (OU)

table 1. Ocular findings at firstexamination.

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Oculodentodigital dysplasia with autosomal recessive inheritance 229

table 2. Review of the literature.

Case(s) report Facial Dental Digital and Ophthalmic Visual Other relevant Possibledismorphisms anomalies skeletal anomalies impairment features inheritance

malformations

Lohmann, 1920 + + + + * * ADMeyer- + + + + + * AD

Schwickerath et al, 1957

Gorlin et al., 1963 + + + + - * ADGillespie, 1964 + + + + + * ARSugar et al., 1966 + + + + + * ADRajic & De Veber, + + + + - * AD

1966Eildelman et al., + + + + + Loss of hearing AR

1967Reisner et al., + + + + + * AD

1969O’Rourk & + + + + - * AD

Bravos, 1969Taysi et al., 1971 + + + + - * ADDudgeon & + + + + + * AD

Chisholm, 1974Gellis & Feingold, + + + + * * AD

1974Guizar-Vazquez + + + + - * AD

et al., 1975Zach, 1975 + + + + * * ADHaines & Rogers, + + + + + * AD

1975Weintraub et al., + + + + + * AD

1975Gemme et al., + + + + + Anophthalmia AD

1976Fara et al., 1977 + + + + + * ADSchneider et al., + + + + + Congenital AD

1977 heart diseaseThoden et al., + + + + * Loss of hearing AD

1977Farman et al., + + + + + Neurological AD

1977 symptomsWooldridge et al., + + + + * * AD

1977Beighton et al., + + + + + Intracranial AR

1979 (1981) calcificationsJudisch et al., + + + + - Loss of hearing AD

1979Audry et al., 1981 + + + + - Neurological AD

symptomsPatton & + + + + - Loss of hearing AD

Laurence, 1985Traboulsi et al., + + + + + Persistent AR

1986 hyperplasticvitreous

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table 2. Continued

Case(s) report Facial Dental Digital and Ophthalmic Visual Other relevant Possibledismorphisms anomalies skeletal anomalies impairment features inheritance

malformations

Dean et al., 1986 + + + + - * ADSchuller et al., + + + + * * AD

1986Levine, 1986 + + + + + Chronic AD

diarrheaBrueton et al., + - + - - * AD

1990Scheutzel, 1991 + + + + * * ADSchrander- + + + + - Neurological AD

Stumpel, & symptomsFranke, 1996

Camera et al., + - + - - * AD1994

Grubs et al., 1994 + + + + * Neurological ADsymptoms

Norton et al., 1995 + + + + - Neurological ADsymptoms

Braun et al., 1996 + + + + + * ADIoan et al., 1997 + + + + - * ADShapiro et al., + + + + * Neurological AD

1997 symptomsThomsen et al., + + + + * * AD

1998Ferencz & Salcz, + + + + + * AD

2000Loddenkemper + + + + + Neurological AD

et al., 2002 symptomsOur patients, + + + + + Intracranial AR

2004 calcifications,cardiomyophaty

+, present; -, absent; *not reported. AD, autosomal dominant; AR, autosomal recessive.Note that visual impairment was present in all probable AR cases.

Ocular findings (Table 1) Inner telecanthus and small palpebralfissures were found in the three boys. On biomicroscopy, the oldest boy was found to have microphthalmos, ellipsoid microcornea plana (at-tenuated sclerocorneal sulcus), with the horizontal diameter greater than the vertical, and bilateral inferior iris coloboma. The second boyhad microphthalmos, microcornea, and secondary glaucoma. Intra-ocular pressure was controlled with topical beta blockers.The youngestbrother had microcornea, and his fundus examination revealed tilted ellipsoid optic disc, filiform retinal vessels, and retinal pigmentepithelium dystrophic changes. Normal crystalline lenses were detected at first examination of all siblings. Collarette, crypts, and pupillary pigment border were absent in both eyes, and there

230 M. Frasson et al.

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Fig. 1. Facial features of the boys (Aand B).

were exuberant remnants of the pupillary membrane in the twoyounger boys. Gonioscopy revealed annular goniosynechiae in all three boys.

The best corrected visual acuity of the second brother was less than0.05 in both eyes. It was impossible to assess the visual acuity in theother two boys.

Oculodentodigital dysplasia with autosomal recessive inheritance 231

Fig. 2. Normal mother with twoyounger boys showing characteristicODDD features.

A B

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Fig. 3. Hands of the second boy (A)and feet of the third boy (B).

Discussion Eye features of ODDD include microphthalmos,microcornea, and glaucoma. A distinctive physiognomy results fromthe small nose, small alae nasi and anteverted nostrils, prominent skull,and hypotrichosis. Dental abnormalities include microdontia, enamelo-genesis imperfecta, and missing teeth. Bilateral camptodactyly of the

232 M. Frasson et al.

Fig. 4. Dental abnormalities of thesecond boy.

A

B

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Fig. 5. Foot radiograph of the secondboy.

Fig. 6. Intracranial calcifications ofthe second and third boys (Athrough D).

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fifth fingers and syndactyly of the fourth and fifth fingers have beendescribed. A constant and characteristic feature of the syndrome is theabsence of the middle phalanx of the second through fifth toes. Someauthors considered the possibility of type lll syndactyly and ODDDbeing separate genetic entities or a disease spectrum. Schrander-Stumpel and Franke reviewed reports of neurologic defects in ODDDand concluded that brain abnormalities (pathologic white matter orcalcifications, for example) may be found. Another less commonfeature is conductive deafness secondary to recurrent otitis media.

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Visual impairment was present in the three boys. Two of our patientshad intracranial calcifications and one had cardiomyopathy, featuresnot very common in this syndrome. These findings corroborate thepleiotropic clinical presentation of ODDD. More severe visual and systemic disabilities appear to characterize the recessive form of thissyndrome. These anomalies require careful follow-up, particularly withrespect to glaucoma, low-vision, cardiomyopathy, and developmentaldelay.

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