Gyrate atrophy of the choroid and retina (GACR) due to deficiency of ornithine aminotransferase is clinically characterized by a triad of progressive chorioretinal degeneration, early cataract formation, and type II muscle fiber atrophy. Characteristic chorioretinal atrophy with progressive constriction of the visual fields leads to blindness at the latest during the sixth decade of life. Patients generally have normal intelligence (summary by Peltola et al., 2002). See 238970 for another hyperornithinemia syndrome.

Neurofibromatosis 2 (NF2) is characterized by bilateral vestibular schwannomas with associated symptoms of tinnitus, hearing loss, and balance dysfunction. The average age of onset is 18 to 24 years. Almost all affected individuals develop bilateral vestibular schwannomas by age 30 years. Affected individuals may also develop schwannomas of other cranial and peripheral nerves, meningiomas, ependymomas, and, very rarely, astrocytomas. Because NF2 is considered an adult-onset disease, it may be underrecognized in children, in whom skin tumors and ocular findings (retinal hamartoma, thickened optic nerves, cortical wedge cataracts, third cranial nerve palsy) may be the first manifestations. Mononeuropathy that occurs in childhood is an increasingly recognized finding; it frequently presents as a persistent facial palsy or hand/foot drop.

Kyrle disease is rare condition that affects the skin. People with this condition generally develop large papules with central keratin (a protein found in the skin, hair and nails) plugs throughout their body. These lesions are typically not painful but may cause severe itching. Although it can affect both men and women throughout life, the average age of onset is 30 years. The cause of the disease is currently unknown; however, it is often associated with certain conditions such as diabetes mellitus, kidney disease, liver abnormalities, and congestive heart failure. In some families, the condition appears to be inherited but an underlying genetic cause has not been identified. Treatment aims to address the associated signs and symptoms and any additional disease that may be present. Lesions often heal spontaneously but new ones continue to develop.

Sponastrime dysplasia is an autosomal recessive spondyloepimetaphyseal dysplasia (SEMD) named for characteristic clinical and radiographic findings, including spine (spondylar) abnormalities, midface hypoplasia with a depressed nasal bridge, and striation of the metaphyses. Additional features include disproportionate short stature with exaggerated lumbar lordosis, scoliosis, coxa vara, limited elbow extension, small dysplastic epiphyses, childhood cataracts, short dental roots, and hypogammaglobulinemia. Radiographically, the abnormalities of the lumbar vertebral bodies are suggested to be the most specific finding because the characteristic metaphyseal striations may not be apparent at young ages. Striking clinical variability in presentation, severity, and associated features has been observed (summary by Burrage et al., 2019).

Any retinitis pigmentosa in which the cause of the disease is a mutation in the OFD1 gene.

Any retinitis pigmentosa in which the cause of the disease is a mutation in the TULP1 gene.

X-linked intellectual disability-retinitis pigmentosa syndrome is characterized by moderate intellectual deficit and severe, early-onset retinitis pigmentosa. It has been described in five males spanning three generations of one family. Some patients also had microcephaly. It is transmitted as an X-linked recessive trait.

Mutations in the CHMP4B gene have been found to cause multiple types of cataract, which have been described as posterior polar, progressive posterior subcapsular, nuclear, and anterior subcapsular. The preferred title/symbol of this entry was formerly 'Cataract, Posterior Polar, 3; CTPP3.'

Mutations in the GJA8 gene have been found to cause several types of autosomal dominant cataract, which have been described as congenital, zonular pulverulent, nuclear progressive, nuclear pulverulent, stellate nuclear, nuclear total, total, and posterior subcapsular. Cataract associated with microcornea, sometimes called the cataract-microcornea syndrome, is also caused by mutation in the GJA8 gene. Before it was known that mutation in the GJB8 gene caused multiple types of cataract, this entry was titled 'Cataract, zonular pulverulent, 1,' with the symbols CZP1, CZP, and CAE1.

Any retinitis pigmentosa in which the cause of the disease is a mutation in the EYS gene.

Retinitis pigmentosa-10 (RP10) is characterized in most patients by early onset and rapid progression of ocular symptoms, beginning with night blindness in childhood, followed by visual field constriction. Some patients experience an eventual reduction in visual acuity. Funduscopy shows typical changes of RP, including optic disc pallor, retinal vascular attenuation, and bone-spicule pattern of pigmentary deposits in the retinal midperiphery. Electroretinography demonstrates equal reduction in rod and cone responses (Jordan et al., 1993; Bowne et al., 2002; Bowne et al., 2006). For a general phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.

Any retinitis pigmentosa in which the cause of the disease is a mutation in the NR2E3 gene.

Retinitis pigmentosa-46 (RP46) is characterized by night blindness, loss of peripheral vision, and reduced visual acuity. Funduscopic findings are typical of RP, including pale optic discs, attenuated retinal vessels, and intraretinal pigment deposits. Electroretinography shows substantial loss of rod and cone photoreceptor function (Hartong et al., 2008). For a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.

Myotonic dystrophy type 2 (DM2) is characterized by myotonia and muscle dysfunction (proximal and axial weakness, myalgia, and stiffness), and less commonly by posterior subcapsular cataracts, cardiac conduction defects, insulin-insensitive type 2 diabetes mellitus, and other endocrine abnormalities. While myotonia (involuntary muscle contraction with delayed relaxation) has been reported during the first decade, onset is typically in the third to fourth decade, most commonly with fluctuating or episodic muscle pain that can be debilitating and proximal and axial weakness of the neck flexors and the hip flexors. Subsequently, weakness occurs in the elbow extensors and finger flexors. Facial weakness and weakness of the ankle dorsiflexors are less common. Myotonia rarely causes severe symptoms. In a subset of individuals, calf hypertrophy in combination with brisk reflexes is notable.

Retinitis pigmentosa-56 (RP56) is an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity (Bandah-Rozenfeld et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.

Retinitis pigmentosa-43 (RP43) is characterized by night blindness in the first decade of life, with progressive loss of peripheral visual fields and reduction in visual acuity. Examination reveals typical features of RP, including waxy pallor of optic disc, attenuated retinal vessels, and bone-spicule pigment in midperipheral retina. Macular edema and/or atrophy has been observed in some patients. Electroretinographic responses are markedly reduced or absent (summary by Huang et al., 1995 and Corton et al., 2010).

Autosomal recessive childhood-onset severe retinal dystrophy is a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously. The most severe cases are termed Leber congenital amaurosis, whereas the less aggressive forms are usually considered juvenile retinitis pigmentosa (summary by Gu et al., 1997). Mutation in TULP1 can also cause a form of autosomal recessive retinitis pigmentosa (RP14; 600132). For a general phenotypic description and a discussion of the genetic heterogeneity of Leber congenital amaurosis, see LCA1 (204000); for retinitis pigmentosa, see 268000.

Any retinitis pigmentosa in which the cause of the disease is a mutation in the PRPF6 gene.

Any retinitis pigmentosa in which the cause of the disease is a mutation in the RBP3 gene.

Microcornea-myopic chorioretinal atrophy-telecanthus syndrome is rare, genetic, developmental defect of the eye disease characterized by childhood onset of mild to severe myopia with microcornea and chorioretinal atrophy, typically associated with telecanthus and posteriorly rotated ears. Other variable features include early-onset cataracts, ectopia lentis, ecotpia pupilae and retinal detachment.

BBS5 is a ciliopathy associated with severe and early-onset retinal dystrophy, postaxial polydactyly, obesity, renal dysfunction, hypogonadism, and learning difficulties (summary by Scheidecker et al., 2015). Patients described by Young et al. (1999) and Moore et al. (2005) with mutations in the BBS5 gene did not have polydactyly. The contribution of BBS5 mutations to all cases of BBS has been estimated at 2% (Li et al., 2004) and 0.40% (Zaghloul and Katsanis, 2009). For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).

Ruijs et al. (2003) reported a Moroccan boy with a chromosomal breakage who died of hepatocellular carcinoma at age 17 years. The boy was noted to have growth retardation at age 3 years; at age 7 he was found to have thoracic kyphosis, frontal bossing, and a delayed bone age of approximately 3 years. He underwent surgery for severe bilateral posterior subcapsular cataracts at age 14. Examination at age 15 showed short stature and low weight, with premature graying of scalp hair, small frontotemporal diameter, small deep-set eyes, bulbous nose with high nasal bridge, small upper lip, and micrognathia. In addition, he had thoracic kyphoscoliosis, sloping shoulders, mild pectus excavatum, moderate bilateral contractures of both elbows, bilateral clinodactyly, and pes planus. At age 17, he developed abdominal pain, and ultrasonography revealed a liver mass; biopsy confirmed hepatocellular carcinoma. Because of the advanced stage, no treatment was possible, and he died 2 months later. Although his parents were not known to be consanguineous, they originated from the same small Moroccan village. Lessel et al. (2014) studied 2 brothers from a nonconsanguineous Australian family of European ancestry who exhibited low body weight, micrognathia, triangular face, muscular atrophy, lipodystrophy, bilateral simian creases, delayed bone age, and mild joint restrictions in the fingers and elbows. In addition, both brothers developed early-onset hepatocellular carcinoma, at ages 16 and 14 years, respectively. The older brother died at age 18 from complications of acute fulminant hepatic failure. Analysis of patient tumor biopsies showed strong focal accumulations of cancer biomarkers as well as a high proliferative index compared to healthy liver or to cells from idiopathic hepatocellular carcinoma.

Any retinitis pigmentosa in which the cause of the disease is a mutation in the ZNF408 gene.

Any early-onset non-syndromic cataract in which the cause of the disease is a mutation in the UNC45B gene.

Spondyloocular syndrome (SOS) is an autosomal recessive disorder characterized by platyspondyly, bone fragility, cataract, retinal detachment, hearing impairment, cardiac defects, and facial dysmorphism (Schmidt et al., 2001; Munns et al., 2015).

Any retinitis pigmentosa in which the cause of the disease is a mutation in the REEP6 gene.

Retinitis pigmentosa-82 with or without situs inversus (RP82) is an autosomal recessive form of retinal degeneration characterized by initial loss of rod photoreceptors, resulting in impaired night vision followed by progressive visual field constriction as both rod and cone photoreceptors die. Some affected individuals have situs inversus (Davidson et al., 2013; Audo et al., 2017). Male patients with infertility due to reduced or absent sperm motility have been reported; female fertility appears to be unaffected (Moye et al., 2019).

Retinitis pigmentosa-83 (RP83) is characterized by onset of night blindness in the first decade of life, with decreased central vision in the second decade of life in association with retinal degeneration. The retinal dystrophy is associated with cataract, and macular edema has also been reported in some patients (Holtan et al., 2019).

Intellectual developmental disorder and retinitis pigmentosa (IDDRP) is characterized by mild to moderate intellectual disability and typical features of RP. Patients experience reduced night vision, constriction of visual fields, and reduced visual acuity; optic disc pallor, attenuated retinal blood vessels, and bone-spicule pigmentation are seen on funduscopy. Attention-deficit/hyperactivity disorder is observed in some patients (Tatour et al., 2017).

SOFM is characterized by marked short stature, oligodontia, mild facial dysmorphism, and motor delay. Endosteal hyperostosis has also been observed, and patients may exhibit some features of progeria (Terhal et al., 2020; Beauregard-Lacroix et al., 2020).