No abstract

X-linked congenital stationary night blindness (CSNB) is a recessive non-progressive retinal disorder characterized by night blindness, decreased visual acuity, myopia, nystagmus and strabismus. Two distinct clinical entities of X-linked CSNB have been proposed. Patients with complete CSNB show moderate to severe myopia, undetectable rod function and a normal cone response, whereas patients with incomplete CSNB show moderate myopia to hyperopia and subnormal but measurable rod and cone function. The electrophysiological and psychophysical features of these clinical entities suggest a defect in retinal neurotransmission. The apparent clinical heterogeneity in X-linked CSNB reflects the recently described genetic heterogeneity in which the locus for complete CSNB (CSNB1) was mapped to Xp11.4, and the locus for incomplete CSNB (CSNB2) was refined within Xp11.23 (ref. 5). A novel retina-specific gene mapping to the CSNB2 minimal region was characterized and found to have similarity to voltage-gated L-type calcium channel alpha1-subunit genes. Mutation analysis of this new alpha1-subunit gene, CACNA1F, in 20 families with incomplete CSNB revealed six different mutations that are all predicted to cause premature protein truncation. These findings establish that loss-of-function mutations in CACNA1F cause incomplete CSNB, making this disorder an example of a human channelopathy of the retina.

Between December 1981 and May 1991, 44 infants and children with congenital toxoplasmosis were referred to our study group. A uniform approach to evaluation and therapy was developed and is described herein along with the clinical characteristics of these infants and children. In addition, case histories that illustrate especially important clinical features or previously undescribed findings are presented. Factors that contributed to the more severe disabilities included delayed diagnosis and initiation of therapy; prolonged, concomitant neonatal hypoxia and hypoglycemia; profound visual impairment; and prolonged, uncorrected increased intracranial pressure with hydrocephalus and compression of the brain. Years after therapy was discontinued, three children developed new retinal lesions (without loss of visual acuity when therapy for Toxoplasma gondii was initiated promptly), and three children experienced a new onset of afebrile seizures. Most remarkable were the normal developmental, neurological, and ophthalmologic findings at the early follow-up evaluations of many--but not all--of the treated children despite severe manifestations, such as substantial systemic disease, hydrocephalus, microcephalus, multiple intracranial calcifications, and extensive macular destruction detected at birth. These favorable outcomes contrast markedly with outcomes reported previously for children with congenital toxoplasmosis who were untreated or treated for only 1 month.