Neuro-Ophthalmology, 31:55–57, 2007Copyright ©c Informa HealthcareISSN: 0165-8107DOI: 10.1080/01658100701285216

A Tunisian Case of Oculo-dento-digitalSyndrome Revealed by Spastic Paraplegia

Amel Boughammoura-Bouatay, Saber Chebel,Mouna Aissi andMahbouba Frih-AyedDepartment of Neurology,University Hospital of FattoumaBourguiba, Monastir, Tunisia

ABSTRACT Oculo-dento-digital syndrome (ODD) is a rare congenital disorderthat associates eye and facial abnormalities, defects in teeth enamel and typeIII syndactyly. It is a genetic disorder inherited in an autosomal dominantfashion and displays high penetrance but variable clinical expression. A fewpatients with ODD syndrome also manifest spastic paraparesis. The authorsreport a sporadic case with ODD syndrome, who was referred for evaluation ofspastic paraplegia associated with bladder dysfunction. The report shows thatODD syndrome can be recognized in late adulthood and revealed by spasticparaplegia. Cerebral MRI must be carried out to complete the phenotyping ofthis syndrome.

KEYWORDS Oculo-dento-digital syndrome; spastic paraplegia

Oculo-dento-digital (ODD) syndrome as defined by Meyer-Schwickerath in19571 is a rare entity (84 cases) that belongs to the ectodermal dysplasias. Itis characterized by developmental abnormalities of the face, eyes, limbs, anddentition. This entity is usually transmitted as an autosomal dominant.1–5 Wereport on a 47-year-old man sporadic case who was admitted to our departmentfor spastic paraplegia associated with bladder dysfunction as the presentation ofthis syndrome.

CASE REPORTBH is a 47-year-old man with no other similar cases in the family; his parents

were not consanguineous. He was admitted to our neurological departmentbecause of difficulty walking, associated with sphincter dysfunction. In 2002 heunderwent bilateral cataract surgery. He had been hospitalized 3 months beforefor dysuria and pollakiuria related to repeat urinary infections. Investigationsshowed bilateral urethral calcification.

The patient complained for 2 years of fatigability and difficulty in walk-ing and frequent falls. Physical examination showed facial dysmorphism, in-cluding narrow nose with hypoplastic alae nasi and thin, anteverted nos-trils; narrow palpebral fissures; and bilateral microcornea and microphtalmi(Fig. 1), along with bilateral complete syndactyly of the fourth and fifth fingers(type III syndactyly) (Fig. 2). These signs are associated with microdontia,caries, enamel hypoplasia, and partial anodontia. We noted also on neuro-logical examination a spastic paraplegia with quadripyramidal syndrome pre-dominating in the lower limbs with exaggerated tendon reflexes in all limbs,

Accepted 3 February 2007.

Address correspondence to MahboubaFrih-Ayed, Department of Neurology,University Hospital of FattoumaBourguiba, Monastir, Tunisia.E-mail: mahbouba.ayed@rns.tn

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FIGURE 1 Photo of patient showing facial dysmorphy.

especially the lower limbs, bilateral Babinski sign, andpes cavus bilaterally. There were no cerebellar or sensorydisorders. Cranial nerves were normal. Ophthalmologicexamination showed vision limited to light perceptionbilaterally, with bilateral papillary pallor, without irisanomalies. Cerebral MRI showed bilateral signal hyper-intensity in the occipital periventricular areas in T2 andflair sequences with bilateral putaminal hypersignal in-tensities in the T1 sequence (Figs. 3 and 4). Audiogramwas normal. Biological tests, including hemogram, in-flammatory, immunological, and metabolic tests, werenormal. Oculo-dento-digital syndrome was diagnosed.The patient’s daughter, aged 13 years, was examined;she had normal physical and ophthalmological exami-nation, without syndactyly.

DISCUSSIONOur patient completes the criteria of the ODD syn-

drome, a congenital disorder that affects the develop-ment of the face, eyes, limbs, and dentition. Facially,affected patients exhibit a narrow nose with hypoplasticalae nasi and thin, anteverted nostrils, narrow palpebralfissures and bilateral microcornea often with anomaliesof the iris.1,3–6 Secondary glaucoma occurs in a numberof patients.4 Bilateral complete syndactyly of the fourthand fifth fingers (type III syndactyly) is the characteristicdigital malformation. The third finger may occasionallybe involved and associated camptodactyly is a commonfinding.1–6 In addition, there is generalized hypoplasiaof the enamel.4–6 Less common features include thin,sparse hair and conductive deafness secondary to re-current otitis media. Symptoms of spastic bladder orgait disturbances are the usual presenting neurologicalmanifestations evident by the second decade of life.A number of authors have reported spastic paraparesisor lower limb weakness in association with ODD in

FIGURE 2 Photo of patient’s hand showing bilateral type III syn-dactyly.

both sporadic and familial cases.3–7,10,11 However fewcases describing this symptom as the initial manifesta-tion of the disease,7–12 this last suggests the presenceof clinical and phenotypic variability of this syndromeeven in the same family. Some authors propose that

FIGURE 3 Cerebral MRI T2 sequence showing leukoen-cephalopathy in the occipital periventricular areas and cerebralatrophy.

A. Boughammoura-Bouatay et al. 56

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FIGURE 4 Cerebral MRI T1 sequence showing bilateral basalganglia hypersignal intensities.

this syndrome must be limited to neurological symp-toms so MRI should be systematically undertaken seek-ing signal abnormalities of the white matter.8,9 Mag-netic resonance imaging demonstrated an underlyingleukodystrophy and it has, therefore, been proposedthat the definition of ODD be widened to include thesefeatures.8,9 This syndrome is an autosomal dominantdisorder with variable expression but in 50% of casesreported, the occurrence is sporadic. Fewer cases of af-fected patients with normal parents were reported sug-gesting recessive transmission; the phenotype of thesepatients seems to be more severe than those from adominant transmission.12 In linkage studies of 6 fam-ilies with ODD syndrome, Gladwin et al. mapped thelocus to 6q22-q24.10 Since that time many mutations ofthe expressed gene GJA1, which encodes the gap junc-tion protein connexin 43, have been shown to underlieODD syndrome.1,14–16

REFERENCES[1] Meyer-Schwickerath G, Gruterich E, Weyers H. Mikroph-

thalmssyndrome. Klin Monatsbl Augenheilkd. 1957;131:18–30.

[2] Sugar HS, Thompson JP, Davis JD. The oculodento-digital dysplasiasyndrome. Am J Ophthalmol.1966;61:1448–1451.

[3] Dudgeon J, Chisholm IA. Oculo-dento-digital dysplasia. Trans Oph-thalmol Soc UK. 1974;94:203–210.

[4] Sugar HS. Oculo-dento-digital dysplasia syndrome with angle-closure glaucoma. Am J Ophthalmol.1978;86:36–38.

[5] Reisner SH, Kott E, Bornstein B, Salinger H, Kaplan I, GorlinRJ. Oculo-dento-digital dysplasia. Am J Dis Child. 1969;118:600–607.

[6] Fara M, Horak I, Hrivnakova J, Kapras J, Nova M, StloukalovaM. Oculo-dento-digital dysplasia. Acta Chir Plast. 1977;19:110–122.

[7] Nivelon-Chevallier A, Audry D, Audry F, Dumas R. Dysplasie oculo-dento-digitale: a propos d’un cas avec paraplegie spasmodique. JGenet Hum. 1981;29:171–179.

[8] Gutmann DH, Zackai EH, McDonald-McGinn DM, Fischbeck KH,Kamholz J. Oculo-dento-digital dysplasia syndrome associated withabnormal cerebral white matter. Am J Med Genet.1990;41:18–20.

[9] Norton KK, Carey JC, Gutmann DH. Oculo-dento-digital dysplasiawith cerebral white matter abnormalities in a two-generation family.Am J Med Genet. 1995;57: 458–461.

[10] Gladwin A, Donnai D, Metcalfe K, et al. Localization of a gene foroculo-dento-digital syndrome to human chromosome 6q22-q24.Hum Mol Genet. 1997;6:123–127.

[11] Nguyen K, Philip N, Suchet L, Azulay JP, Pouget J. Progressive spasticparaplegia as a presentation of oculo-dento-digital syndrome. RevNeurol (Paris). 2004;160: 83–85.

[12] Traboulsi EI, Faris BM, Der kaloustian VM. Persistent hyperplasticprimary vitreous and recessive oculodentoosseous dysplasia. Am JMed Genet. 1986;24: 95–100.

[13] Vasconcellos JPC, Melo MB, et al. A novel mutation in the GJA1gene in a family with oculo-dento-digital dysplasia. Arch Ophthal-mol. 2005;123:1422–1426.

[14] Paznekas WA, Boyadjiev SA, Shapiro RE, et al. Connexin (GJA1)mutations cause the pleiotropic phenotype of oculo-dento-digitaldysplasia Am J Hum Genet. 2003;72:408–418.

[15] Shibayama J, Paznekas W, Seki A, et al. Functional characterizationof connexin43 mutations found in patients with oculo-dento-digitaldysplasia. Circ Res. 2005;96(10): e83–91.

[16] Richardson R, Donnai D, Meire F, Dixon MD. Syndactyly observed inoculo-dento-digital syndrome/type III expression of Gja1 correlateswith the phenotype. J Med Genet. 2004; 41:60–67.

57 Oculo-dento-digital Syndrome and Spastic Paraplegia

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