Leber Congenital Amaurosis - Differential Diagnosis, Ophthalmological and Neuroradiological Report of 18 Patients

Abstract

Between 1985 and 1995 eighteen babies, presenting to our department with absent visual contact and roving eye movements, showed a non-recordable flash electroretinogram (fERG). This was confirmed when repeated after a one-year interval. In four patients with developmental delay an underlying systemic disorder was diagnosed after a thorough pediatric neurological evaluation: Senior Loken syndrome, neuroaxonal dystrophy, ceroid lipofuscinosis and a yet unclear metabolic disorder were the revised diagnoses. The fourteen remaining patients were diagnosed as having primary idiopathic Leber Congenital Amaurosis (LCA). Three of them showed developmental delay. In all three cerebellar abnormalities were visualized on brain computed tomography (CT) and/or magnetic resonance imaging (MRI). Brain CT of the other eleven patients with age appropriate development was normal. We conclude that LCA is a diagnosis of exclusion and a cautious approach with a thorough history and pediatric neurological examination is necessary to exclude a more global pediatric neurological disorder.

Genetic analysis of strictly defined Leber congenital amaurosis with (and without) neurodevelopmental delay

“…Later reappraisals of children originally diagnosed as LCA with neurodevelopmental delay can reveal the presence of a syndrome that was not initially apparent,3 13 24 25 particularly when there was no initial genetic diagnosis to confirm non-syndromic LCA. In this study, we document neurodevelopmental delay in a subset of children with genetically confirmed LCA due to recessive RPGRIP1 and GUCY2D mutations.…”

CRB1-Related Leber Congenital Amaurosis: Reporting Novel Pathogenic Variants and a Brief Review on Mutations Spectrum

“…Therefore, these diseases need to be discriminated from LCA as an isolated ocular disease. However, occasionally, this differentiation cannot be achieved by clinical and paraclinical investigations, especially in the early childhood [23,24] . Moreover, to date, 321 genes and loci on RetNet database have been linked to inherited retinal dystrophies, which some of them such as early onset Retinitis pigmentosa (RP) and CRD may have similar features with LCA.…”

Cerebello-oculo-renal syndromes including Arima, Senior-L�ken and COACH syndromes: More than just variants of Joubert syndrome

“…The frequency and severity of CVH are unknown, as we excluded any patients in whom the status of the vermis could not be determined [Casteels et al, 1996;Clarke et al, 1992;Delaney et al, 1978;Fernandez-Rodriguez et al, 1990;Proesmans et al, 1975;Waldherr et al, 1982;Warady et al, 1994]. However, we expect all patients to have CVH and the associated brainstem malformation.…”