Congenital tritanopia is a rare disease with an autosomal dominant inheritance pattern [1]. It is characterized by tritanopic color vision defects, a normal fundus, and normal visual acuity (Fig. 2.116). Both rod and cone compo- nents of standard full-field ERGs are normal.
Congenital tritanopia and dominantly inherited juvenile optic atrophy (DIJOA) have
several clinical characteristics in common. In addition to having a dominant hereditary pattern, patients with DIJOA may also have tritanopic color vision defects [2]. However, these patients may have slightly to moderately reduced visual acuity, visual field defects, and temporal pallor of the optic disk (Fig. 2.117).
The severity of these abnormalities varies even
2.16 Congenital Tritanopia
—Differential Diagnosis of Dominantly Inherited Juvenile Optic Atrophy
Fig. 2.116. Fundus photographs (top) and farnsworth dichotomous Panel D-15 test (bottom) from two patients with congenital tritanopia. The patients are 31-year-old woman (left) and her father, 67-year-old man (right)
2.16 Congenital Tritanopia 141 RDI2(104%) 9/9/05 7:54 PM Page 141
142 2 Hereditary Retinal and Allied Diseases
Fig. 2.117. Fundus photographs (top) and Farnsworth dichotomous Panel D-15 test (bottom) for three patients with dominantly inherited juvenile optic atrophy. (From Tarasaki et al. [2])
within the same family. Thus, in patients with minimal alterations, the changes in the visual acuity and visual field may be so subtle that a definitive diagnosis cannot be made unless other, more obviously affected family members are examined.
It had been hypothesized that the two dis- eases may be the same clinical entity [3, 4].
However, as shown in Fig. 2.118, the blue (S) cone ERG is unrecordable in patients with con- genital tritanopia but is within the normal range in those with DIJOA [5]. These findings supported the argument that congenital tri- tanopia and DIJOA are not the same disease.
The abnormal S-cone ERG in patients with con- genital tritanopia indicates a retinal origin of
the tritan defect, most likely in the blue cone itself. On the other hand, the normal blue cone ERG in patients with DIJOA indicates that the tritan defect is caused by disturbances of the visual pathway proximal to the layer of origin of the ERG, most likely in the optic nerve.
This hypothesis has been proven to be con- clusively correct by molecular genetic analyses.
In 1992 we detected two point mutations in the gene encoding the blue-sensitive opsin, each leading to an amino acid substitution [6]. These findings showed that these mutations cause tri- tanopia (Fig. 2.119). On the other hand,Votruba et al. detected the genetic mutation (OPA1) locus to be within a 2 CM interval of chromo- some 3q in patients with DIJOA [7].
RDI2(104%) 9/9/05 7:54 PM Page 142
2.16 Congenital Tritanopia 143
References
1. Wright WD (1952) The characteristics of the tritanopia. J Opt Soc Am 42:509–521
2. Terasaki H, Miyake Y, Awaya S, Horio N (1995) Visual functions of dominantly inherited juvenile optic atrophy. Acta Soc Ophthalmol Jpn 99:964–
971
3. Krill AE, Smith VC, Pokorny J (1970) Similarities between congenital tritan defects and dominant opticus-atrophy: coincidence or identity? J Opt Soc Am 60:1132–1139
4. Krill AE, Smith VG, Pokorny J (1971) Further studies supporting identity of congenital tritanopia
and hereditary dominant optic atrophy. Invest Ophthalmol 15:457–465
5. Miyake Y, Yagasaki K, Ichikawa H (1985) Differen- tial diagnosis of congenital tritanopia and domi- nantly inherited juvenile optic atrophy. Arch Ophthalmol 103:1496–1501
6. Weitz CJ, Miyake Y, Shinzato K, Montag E, Zrenner E, Went LN, Nathans J (1992) Human tritanopia associated with two amino acid substitutions in the blue-sensitive opsin. Am J Hum Genet 50:498–507 7. Votruba M, Moore AT, Bhattacharya SS, et al. (1997)
Genetic refinement of dominant optic atrophy (OPA1) locus to within in a 2 CM interval of chro- mosome 3q. J Med Genet 34:117–121
Fig. 2.118. Superimposed blue (S)-cone ERGs recorded from normal subjects, two patients with congenital tritanopia, and four cases of dominantly inherited juvenile optic atrophy (DIJOA). (From Miyake et al. [5])
Fig. 2.119. Model of the blue-sensitive opsin protein primary structure in relation to the lipid bilayer. Open circles, amino acids; filled circles, sites of G79R (left) and S241P (right).
(From Weitz et al. [6]) RDI2(104%) 9/9/05 7:54 PM Page 143
