PURPOSE: Joubert syndrome (JS) is an inherited autosomal recessive or X-lined disorder characterized by a congenital malformation of the mid-hindbrain and a large spectrum of clinical features. It is estimated that retinal dystrophy is present in association with the typical neurological findings in about one-third of the patients. The aim of this study is to better characterize the macular region in JS patients with and without retinal dystrophy.
METHODS: We describe six individuals affected by JS as demonstrated by the presence of the typical "molar tooth sign" on MRI. The presence of retinal dystrophy was assessed by fundus examination and electrophysiology by means of full-field electroretinogram (ERG) and visual evoked potentials (VEP) at five spatial frequencies (300-15 min of arc). The macular region was examined with spectral domain optical coherence tomography (SD-OCT). All the exams were performed in awake conditions. All the patients underwent next-generation-sequencing analysis of known JS genes.
RESULTS: Pathogenic biallelic variants in either the INPP5E gene or the AHI1 gene were detected in two pairs of siblings, all positive for retinal dystrophy. Genetic testing yielded no results in the remaining two patients, one with bilateral coloboma and retinal dystrophy and the other with normal fundus appearance. Decimal best-corrected visual acuity was between 0.1 and 1.0. In the two pairs of siblings, SD-OCT revealed a posterior staphyloma centred on the fovea, in one case associated with cystoid macular oedema. Macular morphology was just slightly altered in the fifth patient and completely normal in the last patient. Refractive error was between + 2.50 diopter sphere (DS) and - 8 DS and - 4 diopter cylinder ax 45°. ERG waves were markedly lower than the normal limits in both scotopic and photopic components in the two pairs of siblings and in the fifth subject, with VEP P100 latencies and amplitudes delayed and reduced in all spatial frequencies. ERG and VEP were within normal limits in the last patient.
CONCLUSIONS: To our knowledge, macular staphyloma has not been described before in JS. Further work is warranted to assess the true prevalence of staphyloma in JS and its connection to retinal dystrophy.