MedGen

Early-onset neurodegeneration in the human retina can lead to Leber congenital amaurosis (LCA), the most severe human form of inherited photoreceptor-neuron degeneration resulting in congenital blindness, with an incidence of approximately 1 in 80,000 (summary by Koenekoop et al., 2012). NMNAT1 mutations have been observed to cause severe and rapidly progressive macular degeneration, leading to severe central atrophy with an appearance of congenital macular coloboma in the neonatal period, as well as an unusual early-onset atrophy of the optic nerve (Perrault et al., 2012). Some patients present with later onset and milder phenotype than typical LCA (Kumaran et al., 2021). For a general discussion of the phenotypic and genetic heterogeneity in Leber congenital amaurosis, see LCA1 (204000). [from OMIM]

Paget disease of bone-5 is an autosomal recessive, juvenile-onset form of Paget disease, a disorder of the skeleton resulting from abnormal bone resorption and formation. Clinical manifestations include short stature, progressive long bone deformities, fractures, vertebral collapse, skull enlargement, and hyperostosis with progressive deafness. There is phenotypic variability, with some patients presenting in infancy, while others present later in childhood (summary by Naot et al., 2014). For discussion of genetic heterogeneity of Paget disease of bone, see 167250. [from OMIM]

Age-related macular degeneration (ARMD) is a multifactorial disorder of the central retina that is the most prevalent cause of progressive vision loss in the developed world. As in other chronic age-related diseases, most cases result from interplay between multiple environmental and genetic factors, with a resultant spectrum of phenotypes. In rare cases, ARMD may manifest early, but there is an exponential rise in prevalence after the age of 60 years (summary by Pras et al., 2015). For a phenotypic description and a discussion of genetic heterogeneity of age-related macular degeneration (ARMD), see 603075. [from OMIM]

Cherubism is a childhood-onset, autoinflammatory bone disease characterized by bilateral and symmetric proliferative fibroosseous lesions limited to the mandible and maxilla. The enlargement is usually symmetric in nature. The phenotype ranges from no clinical manifestations to severe mandibular and maxillary overgrowth with respiratory, vision, speech, and swallowing problems. In most affected persons, teeth are displaced, unerupted, unformed, or absent, or may appear to be floating in cystlike spaces; malocclusion, premature exfoliation of deciduous teeth, and root resorption have also been reported. The course and duration of the active process of bone destruction varies between affected individuals; the onset is usually in early childhood, and typically new lesions can occur until puberty. Regression of the lesions occurs as they become filled with bone and remodel during the second and third decade of life. By age 30 years, the facial abnormalities associated with cherubism are not usually recognizable and residual deformity of the jaws is rare. Typically, cherubism is an isolated benign condition; the affected person has normal intellectual skills and is without other physical anomalies. [from GeneReviews]

Scar tissue in the macula. [from HPO]