Achromatopsia is characterized by reduced visual acuity, pendular nystagmus, increased sensitivity to light (photophobia), a small central scotoma, eccentric fixation, and reduced or complete loss of color discrimination. All individuals with achromatopsia (achromats) have impaired color discrimination along all three axes of color vision corresponding to the three cone classes: the protan or long-wavelength-sensitive cone axis (red), the deutan or middle-wavelength-sensitive cone axis (green), and the tritan or short-wavelength-sensitive cone axis (blue). Most individuals have complete achromatopsia, with total lack of function of all three types of cones. Rarely, individuals have incomplete achromatopsia, in which one or more cone types may be partially functioning. The manifestations are similar to those of individuals with complete achromatopsia, but generally less severe. Hyperopia is common in achromatopsia. Nystagmus develops during the first few weeks after birth followed by increased sensitivity to bright light. Best visual acuity varies with severity of the disease; it is 20/200 or less in complete achromatopsia and may be as high as 20/80 in incomplete achromatopsia. Visual acuity is usually stable over time; both nystagmus and sensitivity to bright light may improve slightly. Although the fundus is usually normal, macular changes (which may show early signs of progression) and vessel narrowing may be present in some affected individuals. Defects in the macula are visible on optical coherence tomography.

Multiple congenital anomalies-hypotonia-seizures syndrome-2 (MCAHS2) is an X-linked recessive neurodevelopmental disorder characterized by dysmorphic features, neonatal hypotonia, early-onset myoclonic seizures, and variable congenital anomalies involving the central nervous, cardiac, and urinary systems. Some affected individuals die in infancy (summary by Johnston et al., 2012). The phenotype shows clinical variability with regard to severity and extraneurologic features. However, most patients present in infancy with early-onset epileptic encephalopathy associated with developmental arrest and subsequent severe neurologic disability; these features are consistent with a form of developmental and epileptic encephalopathy (DEE) (summary by Belet et al., 2014, Kato et al., 2014). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. For a discussion of genetic heterogeneity of MCAHS, see MCAHS1 (614080). For a discussion of nomenclature and genetic heterogeneity of DEE, see 308350. For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).

Macular dystrophies are inherited retinal dystrophies in which various forms of deposits, pigmentary changes, and atrophic lesions are observed in the macula lutea, the cone-rich region of the central retina. Vitelliform macular dystrophies (VMDs) form a subset of macular dystrophies characterized by round yellow deposits, usually at the center of the macula and containing lipofuscin, a chemically heterogeneous pigment visualized by autofluorescence imaging of the fundus (summary by Manes et al., 2013). Vitelliform macular dystrophy-4 (VMD4) is characterized by late-onset moderate visual impairment, small satellite drusen-like lesions in the foveal area, preservation of retinal pigment epithelium (RPE) reflectivity, deposits above the RPE between the ellipsoid and outer segment interdigitation lines on spectral-domain optical coherence tomography (SD-OCT), and normal or borderline results on electrooculography (EOG) (Meunier et al., 2014). In most families with VMD4 caused by compound heterozygous or homozygous mutations in IMPG1, asymptomatic heterozygous carriers have been found to have fundus changes (Manes et al., 2013; Brandl et al., 2017). Brandl et al. (2017) examined patients with VMD4, caused by mutation in the IMPG1 gene, and patients with VMD5 (616152), caused by mutation in the IMPG2 gene, and observed strikingly similar phenotypic characteristics. They noted that retinal lesions progressed in consecutive stages, with the initial development of a single vitelliform lesion in the central macula, with detachment of the neurosensory retina and hyperreflective material located above a preserved Bruch membrane/RPE on SD-OCT. Next, resorption of the hyperreflective material occurs, leaving behind a dome-shaped, optically empty cavity; alternatively, the foveal cavity formed by retinal detachment may become successively filled with material. Finally, there is collapse of the cavity with central retinal atrophy and loss of RPE, resulting in the most pronounced loss of visual acuity. The authors also noted that symptoms tended to be more severe in patients with IMPG1 mutations. For a discussion of genetic heterogeneity of vitelliform macular dystrophy, see VMD1 (153840).

Macular dystrophies are inherited retinal dystrophies in which various forms of deposits, pigmentary changes, and atrophic lesions are observed in the macula lutea, the cone-rich region of the central retina. Vitelliform macular dystrophies (VMDs) form a subset of macular dystrophies characterized by round yellow deposits, usually at the center of the macula and containing lipofuscin, a chemically heterogeneous pigment visualized by autofluorescence imaging of the fundus (summary by Manes et al., 2013). Vitelliform macular dystrophy-5 (VMD5) is characterized by late-onset moderate visual impairment, preservation of retinal pigment epithelium (RPE) reflectivity, deposits above the RPE between the ellipsoid and outer segment interdigitation lines on spectral-domain optical coherence tomography (SD-OCT), and normal or borderline results on electrooculopathy (EOG) (Meunier et al., 2014). Brandl et al. (2017) examined patients with IMPG2- and IMPG1 (602870)-associated VMD (see VMD4; 616151) and observed strikingly similar phenotypic characteristics. They noted that retinal lesions progressed in consecutive stages, with the initial development of a single vitelliform lesion in the central macula, with detachment of the neurosensory retina and hyperreflective material located above the seemingly preserved Bruch membrane/RPE seen on SD-OCT. Next, resorption of the hyperreflective material occurs, leaving behind a dome-shaped, optically empty cavity; alternatively, the foveal cavity formed by retinal detachment may become successively filled with material. Finally, there is collapse of the cavity with central retinal atrophy and loss of RPE, resulting in the most pronounced loss of visual acuity. The authors also noted that symptoms tended to be more severe in patients with IMPG1 mutations. For a discussion of genetic heterogeneity of vitelliform macular dystrophy, see VMD1 (153840).