Sarthak Das and Thirunavukkarasu Arun Babu*

Poor vision in a growing child can affect all domains of development [1]. Early diagnosis of poor vision in infants is extremely challenging as they are unable to express sensory loss or cooperate for clinical and equipment-based testing [2]. We report one such infant who presented with repetitive eye poking.

A 1-year-old female child born out of a second degree consanguineous marriage presented with complaints of not picking up objects, looking downwards without making eye contact, and with repetitive eye poking since three months of life. There was no history of head or ocular injury and no family history of visual impairment. The infant was born at term following an uneventful antenatal period. Infant’s growth and development were appropriate for age. Infant had photophobia, bilateral nystagmus and sluggish pupillary reflex but was able to fix and follow light at a distance of 30 cm. Slit lamp examination revealed normal anterior segment and no evidence of pigmentary retinopathy on fundus examination. Differential diagnosis considered at this point were optic nerve hypoplasia, Leber’s congenital amaurosis (LCA), high refractory errors, early onset rod-cone dystrophy, achromatopsia and cortical visual impairment. Both scotopic and photopic electroretinogram (ERG) were unrecordable. Brain MRI did not show any abnormality. In view of poor vision since birth, nystagmus, normal development, normal fundus, normal brain imaging and flat ERG, a provisional diagnosis of LCA was made. Clinical exome sequencing showed a homozygous missence variation in exon 9 of GUCY2D gene (chr17:g.7915502G>A; Depth 60x) that results in the amino acid substitution of glutamic acid for glycine at codon 597(p.Gly597Glu; ENST00000254854.4) in the tyrosine kinase domain of the GUCY2D protein, confirming diagnosis of LCA type 1. Child is currently under visual rehabilitation therapy and follow-up. Genetic counselling during next pregnancy identified the same defect in the fetus, leading to medical termination.

LCA, an autosomal recessive disorder, is a rare cause of congenital blindness with a prevalence of 2-3 per million, occurring due to degeneration of retinal photoreceptor cells [1].　 FDA approved gene therapy (voretigene neparvovecrzyl) is available for those with RPE65 mutation [4]. Infants present with progressive poor vision since birth, nystagmus, photophobia, hyperopia, keratoconus and a classic behavioral pattern, Franceschetti oculo-digital sign, which involves repetitive poking, pressing, and rubbing of eyes with hand. These oculo-digital mannerisms mechanically stimulate dysfunctional retinal photoreceptors by production of phosphene, but can lead to atrophy of orbital fat and enopthalmos [4]. Though characteristic of LCA, oculo-digital sign can also be a nonspecific marker of poor vision in infants.

Acknowledgement: Dr Pratyusha Ganne, Assistant Professor of Opthalmology, AIIMS, Mangalagiri, for assistance in managing this case and drafting this manuscript.

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2. Suppiej A, Marino S, Reffo ME, et al. Early onset retinal dystrophies: Clinical clues to diagnosis for paediatricians. Ital J Pediatr. 2019;45:168.

3. Han J, Rim JH, Hwang IS, et al. Diagnostic application of clinical exome sequencing in Leber congenital amaurosis. Mol Vis. 2017;23:649-59.

4. Takkar B, Bansal P, Venkatesh P. Leber’s congenital amaurosis and gene therapy. Indian J Pediatr. 2018;85: 237-42.