Are Complete and Incomplete Cases of CSNB Really Nonprogressive

Long-term follow-up of the corrected visual acuity in patients with complete and incomplete CSNB [24] is shown in Fig. 2.76. For both types of CSNB, most patients do not show significant changes or even slight improvement in their visual acuity during the long follow-up period. This strongly indicates that both types of CSNB are nonprogressive, at least when assessed by visual acuity.

The full-field ERGs also show little decrease in amplitude during long-term follow-up; an example is shown in Fig. 2.77. The single flash ERG (rod-cone mixed) was recorded from a patient with incomplete CSNB in 1970 and repeated again under similar conditions in 2002. After 32 years, the ERG did not decrease in amplitude, but the b-wave amplitude had increased [10]. This patient was found to have the mutated CACNA1F gene, as in most patients with incomplete CSNB [11]. In addition to these findings, families with X-linked complete and incomplete CSNB sometimes have a grandfather and grandson who, despite the large difference in age, have essentially the same clinical findings. These observations suggest that these two disorders are essentially stationary.

However, among the patients with a CACNA1F gene mutation, we have found that some had a progressive clinical course and severely deteriorated visual function [25, 26]. The full-field ERGs of a 31-year-old man showed typical findings of incomplete CSNB (Fig. 2.78A). This patient had a hemizygous Arg913 stop mutation in the CACNA1F gene [25] (Fig. 2.78B). The fundus, fluorescein angiograms, and visual fields are shown in Fig. 2.79. The patient had atrophic retinal lesions around the inferior vascular arcades in both eyes that resembled that of pigmented paravenous retinochoroidal atrophy or sectorial retinitis pigmentosa. Fluorescein angiography revealed window defects in the areas corresponding to the atrophy, and Goldmann kinetic perimetry detected relative scotomas in the same areas.

Fundus photographs of another two brothers [26] are shown in Fig. 2.80. The younger, 56-year-old brother (Fig. 2.80A,B) had optic atrophy, attenuated retinal vessels, and slightly diffuse pigmentary atrophy in both eyes. The older, 64-year-old brother (Fig. 2.80C,D) had optic atrophy and severe chorioretinal degeneration in both eyes. Both patients had progressive decline of visual functions and had an in-frame mutation with deletion and insertion in exon 4 of the CACNA1F gene. In both patients, the mixed rod-cone ERG had a negative configuration, which is characteristic of incomplete CSNB. However, OPs were absent, and the rod and cone ERGs, which are not usually seen in patients with incomplete CSNB, were unrecordable (Fig. 2.81, cases 1, 2).

These findings of three patients in two pedigrees indicated that mutations of the CACNA1F gene often lead to ERG findings that correspond to those for incomplete CSNB, but the mutations also occasionally lead to ERG changes associated with other retinal dystrophies that have retinal and optic disk atrophy with progressively decreasing visual function.

Fig. 2.76. Changes in visual acuity in patients with complete and incomplete CSNB during long-term follow-up periods. (From Miyake et al. [24])

Fig. 2.77. Mixed rod-cone ERGs recorded in 1970 and 2002 from a patient with incomplete CSNB. (From Miyake [10])

Fig. 2.76. Changes in visual acuity in patients with complete and incomplete CSNB during long-term follow-up periods. (From Miyake et al. [24])

Fig.2.78. A Full-field ERGs recorded from a normal subject and a patient with a CACNA1Fgene mutation.B Nucleotide sequence of CACNA1F using a sense primer in this patient. A hemizygous nonsense mutation of C to T in axon 24 (Arg913stop) is shown.The arrow indicates the position of the mutation. (From Nakamura et al. [25], with permission)

Fig.2.78. A Full-field ERGs recorded from a normal subject and a patient with a CACNA1Fgene mutation.B Nucleotide sequence of CACNA1F using a sense primer in this patient. A hemizygous nonsense mutation of C to T in axon 24 (Arg913stop) is shown.The arrow indicates the position of the mutation. (From Nakamura et al. [25], with permission)

Fig. 2.79. Fundus photographs (A, B), fluorescein angiograms (C, D), and Goldmann kinetic visual fields (E) of the patient with a CACNA1F gene mutation shown in Fig. 2.78. Right eye (A, C) and left eye (B, D) show an atrophic retinal region around the inferior vascular arcade with hyperfluorescence due to RPE alterations.Visual fields show a relative scotoma in the area corresponding to retinal atrophy (E). (From Nakamura et al. [25], with permission)

Fig. 2.79. Fundus photographs (A, B), fluorescein angiograms (C, D), and Goldmann kinetic visual fields (E) of the patient with a CACNA1F gene mutation shown in Fig. 2.78. Right eye (A, C) and left eye (B, D) show an atrophic retinal region around the inferior vascular arcade with hyperfluorescence due to RPE alterations.Visual fields show a relative scotoma in the area corresponding to retinal atrophy (E). (From Nakamura et al. [25], with permission)

Cat Scratch Disease Eye

Fig.2.80. Fundi of two patients with CACNA1F mutations (cases 1 and 2).Case 1 shows optic atrophy, attenuated retinal vessels, and diffuse RPE atrophy in both eyes. Case 2 shows optic atrophy, attenuated retinal vessels in both eyes, and severe chorioretinal degeneration in the left eye. (From Nakamura et al. [26], with permission)

Fig.2.80. Fundi of two patients with CACNA1F mutations (cases 1 and 2).Case 1 shows optic atrophy, attenuated retinal vessels, and diffuse RPE atrophy in both eyes. Case 2 shows optic atrophy, attenuated retinal vessels in both eyes, and severe chorioretinal degeneration in the left eye. (From Nakamura et al. [26], with permission)

Complete Incomplete Csnb
Fig. 2.81. Full-field ERGs recorded from a normal subject, a patient with typical incomplete CSNB, and two patients with optic atrophy and CACNA1F gene mutations (cases 1 and 2). (From Nakamura et al. [26], with permission)

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