Aland Island eye disease (AIED) is an X-linked recessive retinal disease characterized by fundus hypopigmentation, decreased visual acuity, nystagmus, astigmatism, protan color vision defect (303900), progressive myopia, and defective dark adaptation. Although AIED has been referred to as ... Aland Island eye disease (AIED) is an X-linked recessive retinal disease characterized by fundus hypopigmentation, decreased visual acuity, nystagmus, astigmatism, protan color vision defect (303900), progressive myopia, and defective dark adaptation. Although AIED has been referred to as a form of albinism, there is no misrouting of the optic nerves, which excludes it from the formal diagnosis of classic albinism (King et al., 2001).
Forsius and Eriksson (1964) reported X-linked tapetoretinal degeneration in a family described in a family from the Aland Islands in the Sea of Bothnia. Males in 6 generations were affected with hypopigmentation of the fundus, foveal hypoplasia, marked ... Forsius and Eriksson (1964) reported X-linked tapetoretinal degeneration in a family described in a family from the Aland Islands in the Sea of Bothnia. Males in 6 generations were affected with hypopigmentation of the fundus, foveal hypoplasia, marked impairment of vision, nystagmus, myopia, astigmatism, and protan colorblindness. Female carriers showed slight disturbances of color discrimination and electromyographically demonstrable nystagmus. Warburg (1964) described ocular albinism and protanopia in the same Aland Island kindred family. Only 2 of 4 males with ocular albinism showed dyschromatopsia. The absence of characteristic fundus pigmentary pattern in female carriers in the family of Forsius and Eriksson suggested that they had a distinct entity from X-linked Nettleship-Falls ocular albinism (OA1; 300500). Scialfa (1967) reported another family with this disorder. By electron microscopic study of skin biopsies obtained by Forsius in the Island of Aland, O'Donnell and Green (1978) and O'Donnell et al. (1980) concluded that the Forsius-Eriksson type is morphologically distinct from the Nettleship-Falls type of ocular albinism; no macromelanosomes were present. By electrophysiologic studies, van Dorp et al. (1985) showed that there is no misrouting of the optic pathways in Aland Eye disease, thus distinguishing it from true albinism. Other differences from albinism, not commented on earlier, included differences in the spontaneous and optokinetic nystagmus. Maumenee (1986) expressed the opinion that this disorder may be a variety of achromatopsia. Weleber et al. (1989) pointed out that newer electrophysiologic techniques, including electroretinography, show many differences between this disorder and OA1; however, the disorder showed some similarities to X-linked incomplete congenital stationary night blindness (300071). Glass et al. (1991,1993) reported studies of a 6-generation family with 9 affected males and 14 obligatory carriers. Clinical features included severely reduced visual acuity, nystagmus, high axial myopia, foveal hypoplasia, and protanomalous color vision deficiency associated with minor fundal depigmentation. Although impaired night vision was not a symptom, psychophysical and electrophysiologic testing showed that both rod and cone function were abnormal in all affected males. No abnormality was detected in carrier females. The findings were similar to those previously reported in both CSNB2A and AIED. Jalkanen et al. (2007) stated that although AIED and CSNB2A are allelic disorders, there are a few distinct differences between the symptoms of the patients in the original AIED family and those described as having CSNB2A. AIED has progressive myopic refraction, foveal dysplasia with no foveal reflex, and a protan defect in color vision (303900), whereas CSNB2A is apparently stationary with a normal fovea and mostly normal color vision, with tritan (190900) or mixed defects in some cases. They suggested that the differences my be attributable to differences in genetic background (i.e., other genes or genetic modifiers). Hawksworth et al. (1995) studied a Welch kindred in which congenital nystagmus and moderate-to-high refractive error segregated as an X-linked trait, with manifestation in some female carriers. Affected males demonstrated myopia, but a high proportion of female carriers and some of the possibly affected males showed hypermetropia. Clinical ophthalmologic examination and electrodiagnostic studies of retinal function were compatible with a diagnosis of either incomplete congenital stationary night blindness or Aland island eye disease. Hawksworth et al. (1995) raised the question of whether the 2 entities are the same.
Wutz et al. (2002) identified mutations in the CACNA1F gene (300110), which is also mutated in the incomplete form of X-linked congenital stationary night blindness (CSNB2A), in a Finnish family and a sporadic Swiss case with an AIED-like ... Wutz et al. (2002) identified mutations in the CACNA1F gene (300110), which is also mutated in the incomplete form of X-linked congenital stationary night blindness (CSNB2A), in a Finnish family and a sporadic Swiss case with an AIED-like phenotype. Reevaluation indicated full compatibility of the patients' ophthalmologic phenotypes with CSNB2A. No CACNA1F mutation by complete DNA sequencing of all 48 exons could be found in a classic AIED family previously shown to map to the pericentromeric region of the X chromosome (Alitalo et al., 1991). Due to similar clinical features of AIED and CSNB2A, Wutz et al. (2002) speculated that the mutation in this family may be located in an intron or in the promoter region. In affected members of the original family with Aland Island eye disease described by Forsius and Eriksson (1964), Jalkanen et al. (2007) identified homozygosity for a 425-bp deletion mutation encompassing exon 30 and portions of adjacent introns of the CACNA1F gene (300110.0008). The mutation was found in heterozygous state in carrier females of this family and was not found in samples from 121 Finnish male control subjects.