Colour vision deficiency and inherited retinal disease: Case

Framing the case

This ten-month-old infant has the classic presentation of a severe congenital retinal dystrophy, the roving eye movements, the nystagmus and the poor fixation with the otherwise normal development, and the framework that organises the case is the electroretinography, the molecular genetic testing and the RPE65 Leber congenital amaurosis. The contrast with the older brother, who carries the benign red-green colour vision deficiency, is the contrast the examiner will probe, because the brother has the stable defect of the normal acuity while the infant has the severe vision loss of the congenital dystrophy. The first priority is the prompt referral to the paediatric ophthalmology service for the electroretinography and the genetic testing, because the treatable RPE65 form must not be missed. [1][3]

Confirming the diagnosis

The ophthalmology service performs the full-field electroretinography, which shows the near-absent rod and cone response, and the pattern electroretinography of the macular pathway, which is also severely reduced. The optical coherence tomography assesses the viability of the retinal cells, which the gene therapy demands, and the fundus autofluorescence maps the retained retina. The molecular genetic testing by the next-generation sequencing panel of the inherited retinal disease genes identifies the biallelic RPE65 mutation, which is the result that opens the door to the gene therapy. The candidate who holds the electrophysiology, the imaging and the panel as the three pillars of the diagnosis earns the marks. [1][9]

The contrast with the colour-deficient brother

The examiner asks the candidate to contrast the infant with the older brother who carries the red-green colour vision deficiency. The brother has the X-linked recessive trait of the OPN1LW and the OPN1MW opsin genes, with the normal acuity, the full field, the healthy fundus and the stable course, and his management is the reassurance and the vocational advice. The infant has the severe congenital retinal dystrophy of the RPE65 gene, with the poor vision, the nystagmus, the attenuated vessels and the near-absent electroretinography, and his management is the gene therapy and the low-vision support. The contrast is absolute, and the candidate who holds it demonstrates the breadth the boards reward. [6][2]

The gene therapy

The voretigene neparvovec is the approved gene therapy for the biallelic RPE65 mutation with the viable retinal cells, and it is delivered as the single subretinal injection of the adeno-associated virus serotype two vector carrying the human RPE65 gene into each eye, on the separate occasions. The Russell phase three trial showed the improvement of the functional vision on the multi-luminance mobility test, and the longer follow-up of Maguire confirmed the durable gain. The treatment is reserved for the RPE65 form, and it is not a cure, because it improves the functional vision rather than the full restoration of the sight, and it carries the surgical risk of the subretinal injection, the inflammation and the cataract. The honest counselling of the family balances the genuine gain against the limitation and the risk. [3][4][11]

The genetic counselling and the family

The genetic counselling addresses the autosomal recessive inheritance of the biallelic RPE65 mutation, the twenty-five-percent recurrence risk for the future children of the same parents, and the carrier testing of the extended family. The candidate explains that the colour-deficient brother is not affected by the RPE65 disease, because the two conditions are separate genes and the separate inheritance, and the colour defect is the benign X-linked trait of the mother's family. The family is supported by the clinical genetics, the social work and the low-vision service, and the infant is enrolled in the early-intervention and the educational support from the diagnosis. [9][11]