Leber congenital amaurosis comprises a group of early-onset childhood retinal dystrophies characterized by vision loss, nystagmus, and severe retinal dysfunction. Patients usually present at birth with profound vision loss and pendular nystagmus. Electroretinogram (ERG) responses are usually nonrecordable. ... Leber congenital amaurosis comprises a group of early-onset childhood retinal dystrophies characterized by vision loss, nystagmus, and severe retinal dysfunction. Patients usually present at birth with profound vision loss and pendular nystagmus. Electroretinogram (ERG) responses are usually nonrecordable. Other clinical findings may include high hypermetropia, photodysphoria, oculodigital sign, keratoconus, cataracts, and a variable appearance to the fundus (summary by Chung and Traboulsi, 2009). For a general description and a discussion of genetic heterogeneity of LCA, see 204000.
Waardenburg and Schappert-Kimmijser (1963) published a pedigree that showed all normal children from 2 affected parents with Leber congenital amaurosis (LCA). The mother had 2 affected sisters and the father was the product of a first-cousin marriage. Keratoconus ... Waardenburg and Schappert-Kimmijser (1963) published a pedigree that showed all normal children from 2 affected parents with Leber congenital amaurosis (LCA). The mother had 2 affected sisters and the father was the product of a first-cousin marriage. Keratoconus (or keratoglobus), a frequent feature of this condition, was not present in either parent but was found in one of the mother's affected sisters. This condition is, of course, not to be confused with Leber optic atrophy. Chung and Traboulsi (2009) noted that LCA2 is distinguished by moderate visual impairment at infancy that progresses to total blindness by mid to late adulthood. One of the unique qualities of LCA2 is that, even with profound early visual impairment, retinal cells are relatively preserved. Morimura et al. (1998) summarized the clinical criteria distinguishing retinitis pigmentosa (RP) from LCA. RP is the diagnosis given to patients with photoreceptor degeneration who have good central vision within the first decade of life. The diagnosis of LCA is given to patients who are born blind or who lose vision within a few months after birth. Both diagnostic entities feature attenuated retinal vessels and a variable amount of retinal pigmentation in older patients and a reduced or nondetectable electroretinogram (ERG) at all ages. Morimura et al. (1998) noted that there was no universally accepted diagnostic term for those patients with retinal degeneration who lose useful (ambulatory) vision during the first few years of life, with ophthalmologists considering such cases as either LCA or severe RP. Yzer et al. (2003) studied 14 patients with early-onset retinal dystrophy from 10 related Dutch families from a genetically isolated population living on a former island in the Netherlands, previously reported by Schappert-Kimmijser et al. (1959), as having a high incidence of LCA. None of the 14 newborns followed objects or made eye contact, leading their parents to suspect visual impairment within the first 3 months of life. All had night blindness, and none had photophobia, and all but 2 children showed early-onset nystagmus or developed nystagmus before 6 years of age. A wide range of visual acuities was observed at first examination, and at follow-up visual acuity had remained relatively stable in 9 patients, whereas in 4 it had deteriorated. In the 7 patients in whom color vision testing could be performed, color vision was severely disturbed and tended to the tritan axis (see 190900). Visual field defects were slightly progressive, but peripheral fields remained relatively stable in 10 patients. ERGs were performed by 3 years of age in 12 patients, of whom 7 had no responses detected (5 within the first year of life); in 4 patients, severely reduced photopic responses were measured with absent scotopic responses, and in only 1 patient were both scotopic and photopic responses measured. Yzer et al. (2003) noted that the age of onset of the retinal dystrophy in these patients suggested LCA, but that several characteristics, including visual acuity, visual fields, and night blindness, led them to classify the phenotype as an early-onset severe retinal dystrophy. Al-Khayer et al. (2004) reported a 35-year-old patient with LCA due to compound heterozygosity for mutations in the RPE65 gene. She had severe visual deficits and had presented in infancy with night blindness, nystagmus, and absent rod and cone electroretinograms. Although in early childhood her visual acuity was 20/60 in both eyes and color recognition was normal, at age 35 years her acuity had declined to 2/200 in the right eye and 1/200 in the left eye.
The existence of at least 2 genetically distinct forms of Leber congenital amaurosis was established by the demonstration of Marlhens et al. (1997) that the disorder can be caused not only by mutations in the gene for retinal ... The existence of at least 2 genetically distinct forms of Leber congenital amaurosis was established by the demonstration of Marlhens et al. (1997) that the disorder can be caused not only by mutations in the gene for retinal guanylate cyclase (600179), but also by mutations in the RPE65 gene. In 2 sibs with LCA2, they identified compound heterozygosity for mutations in the RPE65 gene: a 1-bp deletion (180069.0001) and a nonsense mutation (180069.0002) inherited from the mother and father, respectively. In 13 patients with early-onset severe retinal dystrophy from 9 related Dutch families from a genetically isolated population living on a former island, Yzer et al. (2003) analyzed the RPE65 gene and identified homozygosity for a missense mutation (Y368H; 180069.0009). A patient from another related family was found to be compound heterozygous for Y368H and a splice site mutation (180069.0010). Among 25 unaffected sibs tested, 17 were heterozygous for the Y368H mutation, and 8 did not carry the mutation. The Y368H mutation was found in 3 (3.1%) of 96 unrelated controls from the same isolated Dutch population. Yzer et al. (2003) noted that in a study of the same genetically isolated Dutch population, Schappert-Kimmijser et al. (1959) ascertained 13 LCA patients in 8 families; Yzer et al. (2003) predicted that most if not all of those patients carried the Y368H founder mutation. The Y368H founder mutation was not detected in 86 LCA patients from a different white population or in 94 controls from the Netherlands, but analysis of 75 Dutch patients with autosomal recessive or isolated retinitis pigmentosa revealed the presence of the mutation in heterozygosity in 1 Dutch patient with RP and early-onset vision loss. Al-Khayer et al. (2004) identified compound heterozygosity for mutations in the RPE65 gene (180069.0011 and 180069.0012) in a 35-year-old woman with LCA2.