Dear Editor,
CABP4-related retinal dysfunction (MIM: 610427) is a rare autosomal recessive disorder caused by pathogenic variants in CABP4, a photoreceptor synaptic calcium-binding protein. Initially classified as incomplete congenital stationary night blindness (icCSNB) due to an electronegative scotopic electroretinogram (ERG),[1] it is now recognized as a congenital cone-rod synaptic disorder (CRSD) characterized by predominant cone dysfunction with relatively preserved rod activity.[2,3]
We report the first genetically confirmed case of CABP4-related CRSD from India.
A 29-year-old male presented with poor distance vision, marked photophobia, and horizontal jerk nystagmus since early childhood. Symptoms were nonprogressive, and he preferred dimly lit environments. He was the second child of a second-degree consanguineous marriage, with no family history of ocular disease.
The best-corrected visual acuity was 6/60 in each eye with no refractive error. Color vision testing (Ishihara) revealed total color blindness. Differentials included achromatopsia and cone dystrophy. The anterior segment was unremarkable with no iris transillumination. Fundus examination and widefield fundus autofluorescence (Optos Inc., UK) showed normal optic discs, maculae, and periphery [Fig. 1]. Optical coherence tomography (Cirrus OCT, Carl Zeiss Meditec, USA) demonstrated severe macular thinning with intact ellipsoid zones [Fig. 2]. Full-field ERG (RETeval™, LKC Technologies, USA) revealed a severely depressed dim scotopic response, an electronegative bright-flash scotopic response, and absent photopic responses [Fig. 3].
Figure 1.
Wide-field fundus photo (a) with autofluoroscent image (b) showing a normal disc, macula, mid periphery, and periphery, without any evident atrophic areas or pigmentation
Figure 2.
OCT images of the right (a) and left (b) eyes showing normal foveal contour and well-maintained ellipsoid zones, but severe thinning of the macula (c) in both eyes
Figure 3.
ERG showing a severely depressed dim scotopic response along with an electronegative bright flash scotopic response (a) and a flat photopic response (b)
Next-generation sequencing using a 675-gene ophthalmic panel identified a homozygous nonsense variant in CABP4 (c.646C>T; p.Arg216Ter) on exon 4, previously reported as causative for CRSD.[4,5] The patient was counseled regarding the nonprogressive nature of the condition and the role of carrier testing in future family planning. Parents and the older sister, being asymptomatic and phenotypically normal, were not advised genetic testing.
CABP4 encodes a calcium-binding protein essential for synaptic transmission at photoreceptor terminals.[2] Loss-of-function variants impair cone signaling, explaining the phenotype of low vision, photophobia, nystagmus, and absent photopic responses with relatively preserved scotopic function.[3,4,5] Our case’s phenotype and genotype are consistent with those previously described with this mutation in European cohorts,[4,5] expanding its geographic spectrum.
This case underscores the importance of detailed electrophysiological evaluation combined with genetic testing in unexplained early-onset nystagmus and photophobia, especially in regions with prevalent consanguinity. Accurate molecular diagnosis provides prognostic clarity, prevents misclassification as stationary night blindness, and facilitates appropriate genetic counseling.
In conclusion, we present the first Indian case of CABP4-related CRSD confirmed by molecular testing. Awareness of this rare but distinctive condition can enable early diagnosis, contribute to the growing global understanding of inherited retinal disorders, and aid in the development of potential therapies.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Conflicts of interest:
There are no conflicts of interest.
Funding Statement
Nil.
References
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