Oguchi disease is an autosomal recessive retinal disorder characterized by congenital stationary night blindness (see this term) and the Mizuo-Nakamura phenomenon. Epidemiology Oguchi disease is a very rare condition with approximately 50 cases described in the literature to date. It was originally discovered in Japan where the prevalence is the highest but has been found occasionally in European, American, Pakistani and Indian patients. Clinical description The disease is characterized by congenital stationary night blindness and the Mizuo-Nakamura phenomenon which is a unique morphological and functional abnormality of the retina that presents with a typical golden-yellow or silver-gray discoloration of the fundus in the presence of light that disappears after dark-adaptation and appears again after the onset of light. Patients have non progressive night blindness since young childhood with normal day vision, but they often claim improvement of light sensitivities when they remain a long time in a dark environment.

A number sign (#) is used with this entry because of evidence that Oguchi disease-2 (CSNBO2) can be caused by homozygous mutation in the GRK1 gene (180381) on chromosome 13q34. Description Oguchi disease is a rare autosomal recessive form of congenital stationary night blindness in which all other visual functions, including visual acuity, visual field, and color vision, are usually normal. A typical feature of the disease is a golden or gray-white discoloration of the fundus that disappears in the dark-adapted state and reappears shortly after the onset of light (Mizuo phenomenon). The course of dark adaptation of rod photoreceptors is extremely retarded, whereas that of cones appears to proceed normally (summary by Fuchs et al., 1995). For a general description and a discussion of genetic heterogeneity of Oguchi disease, see CSNBO1 (258100).

Oguchi disease Other names Congenital stationary night blindness, Oguchi type 1 or Oguchi disease 1 [1] Oguchi disease has an autosomal recessive pattern of inheritance. Specialty Neurology Oguchi disease , is an autosomal recessive [2] form of congenital stationary night blindness associated with fundus discoloration and abnormally slow dark adaptation . Contents 1 Genetics 2 Diagnosis 2.1 Differential diagnosis 2.2 Electroretinographic studies 3 Management 4 History 5 References 6 External links Genetics [ edit ] Several mutations have been implicated as a cause of Oguchi disease. These include mutations in the arrestin gene or the rhodopsin kinase gene. [1] Type OMIM Gene Type 1 258100 SAG Type 2 613411 GRK1 The condition is more frequent in individuals of Japanese ethnicity. [3] Diagnosis [ edit ] Oguchi disease present with nonprogressive night blindness since young childhood or birth with normal day vision, but they frequently claim improvement of light sensitivities when they remain for some time in a darkened environment. [ citation needed ] On examination patients have normal visual fields but the fundi have a diffuse or patchy, silver-gray or golden-yellow metallic sheen and the retinal vessels stand out in relief against the background. A prolonged dark adaptation of three hours or more, leads to disappearance of this unusual discoloration and the appearance of a normal reddish appearance.

A number sign (#) is used with this entry because of evidence that this Marfan-like syndrome can be caused by mutation in the gene encoding fibrillin (FBN1; 134797) on chromosome 15q21.1. Clinical Features Glesby and Pyeritz (1989) pointed out that more than half of a large number of patients evaluated in the medical genetics clinic at Johns Hopkins for a possible heritable disorder of connective tissue could not be precisely classified. As a group, these patients showed many manifestations of the Marfan syndrome (154700), including long limbs, deformity of the thoracic cage, striae atrophicae, mitral valve prolapse, and mild dilatation of the aortic root. Clinical clustering did not emerge when patients were stratified by mitral valve prolapse or aortic dilatation. The clinical phenotype of patients with mitral valve prolapse constituted a continuum, from Marfan syndrome at one extreme to isolated mitral valve prolapse due to myxomatous change of the valve leaflets (see 157700).

MASS phenotype is a familial connective tissue disorder similar to Marfan syndrome that affects different people in different ways. MASS is an acronym for features of the disorder that may be present: M itral valve prolapse - a heart condition in which the two valve flaps of the mitral valve in the heart do not close smoothly or evenly, and bulge (prolapse) upward into the left atrium. A ortic root dilation - borderline, non-progressive enlargement of the section of the aorta where the aorta and heart meet. Unlike in Marfan syndrome, aortic complications such as dissection and aneurysm usually do not occur. However some authors believe there may be an increased risk for aortic complications.

A number sign (#) is used with this entry because of evidence that Cole-Carpenter syndrome-2 (CLCRP2) is caused by compound heterozygous mutation in the SEC24D gene (607186) on chromosome 4q26. For a general phenotypic description and discussion of genetic heterogeneity of Cole-Carpenter syndrome, see CLCRP1 (112240). Clinical Features Garbes et al. (2015) reported a German boy with multiple pre- and postnatal fractures and craniofacial malformations. At birth, he was noted to have turricephaly, exophthalmos, downslanting palpebral fissures, angular root of nose, retrognathia, and gaping fontanels. Ultrasound and x-ray examination showed both new and old fractures involving the right clavicle, multiple ribs, and both radii, as well as extensive ossification defects of the cranium and craniosynostosis.

Cole-Carpenter syndrome Autosomal recessive pattern is the inheritance manner of this condition Specialty Medical genetics Cole-Carpenter syndrome is a rare autosomal recessive medical condition in humans. [1] It is characterised by dysmorphic features and a tendency to fractures. Contents 1 Signs and symptoms 2 Genetics 3 Pathogensis 4 Diagnosis 4.1 Differential diagnosis 5 Treatment 6 History 7 References Signs and symptoms [ edit ] This condition is usually diagnosed in infancy. Features of this condition include [ citation needed ] Short trunk Poor growth Hydrocephalus Multiple fractures Craniofacial abnormalities Multisutural craniosynostosis Ocular proptosis Marked frontal bossing Midface hypoplasia Micrognathia Genetics [ edit ] There are three forms of this syndrome. Type 1 has mutations in the protein disulfide-isomerase ( P4HB ) gene located on the long arm of chromosome 17 (17q25). [2] Type 2 have mutations in the protein transport protein Sec24D ( SEC24D ) gene located on the long arm of chromosome 4 (4q26). [3] A third type has been described with a mutation in the cartilage associated protein ( CRTAP ) located on the short arm of chromosome 3 (3p22.3). [4] Clinically these forms are very similar and are best differentiated by gene sequencing. Pathogensis [ edit ] Protein disulfide-isomerase is involved in the hydroxylation of proline residues in preprocollagen.

An extremely rare form of bone dysplasia characterized by the features of osteogenesis imperfecta such as bone fragility associated with multiple fractures, bone deformities (metaphyseal irregularities and bowing of the long bones) and blue sclera, in association with growth failure, craniosynostosis, hydrocephalus, ocular proptosis, and distinctive facial features (e.g. frontal bossing, midface hypoplasia, and micrognathia).

A rare mitochondrial oxidative phosphorylation disorder characterized by a variable clinical phenotype including infantile onset of epileptic encephalopathy, hypotonia, global developmental delay, failure to thrive, complex movement disorder, and liver involvement, as well as childhood onset of severe myoclonus epilepsy, cognitive decline, progressive hearing and visual impairment, and progressive tetraparesis. Serum lactate may be increased, and brain imaging shows variable atrophy and white matter abnormalities.

A rare skin disease that is the most common form of porokeratosis characterized by the presence of several small annular plaques with a distinctive keratotic rim found most commonly on sun-exposed areas of the skin, particularly the extremities. Epidemiology Disseminated superficial actinic porokeratosis (DSAP) prevalence is not precisely known, although DSAP is the most common form of porokeratosis. It is more frequently seen in women, probably because they more readily seek advice for cosmetic concerns. Clinical description The disease usually starts during the third to fourth decade of life (only rarely during childhood). DSAP is characterized by several small (0.5-1 cm), round, pink-brownish plaques, surrounded by a distinctive keratotic rim, corresponding microscopically to the cornoid lamella.

A number sign (#) is used with this entry because of evidence that multiple types of porokeratosis (POROK9) are caused by heterozygous mutation in the FDPS gene (134629) gene on chromosome 1q22. Description Porokeratosis is a rare skin disorder characterized by one or more annular plaques with a surrounding raised horny border that spreads centrifugally. Variants of porokeratosis have been described that differ in morphologic shapes, distribution, and clinical course (Schamroth et al., 1997). However, as noted by Sybert (2010), several families with expression of more than one variant of porokeratosis among members, and individuals expressing more than one variant, have been reported, suggesting that the distinctions among these variants may be artificial. Mutations in the FDPS gene have been found to cause multiple types of porokeratosis, which have been described as disseminated superficial actinic porokeratosis (DSAP) and nonactinic disseminated superficial porokeratosis (DSP).

A number sign (#) is used with this entry because of evidence that disseminated superficial actinic porokeratosis-8 (POROK8) is caused by heterozygous mutation in the SLC17A9 gene (612107) on chromosome 20q13. Description Porokeratosis is a rare skin disorder characterized by one or more annular plaques with a surrounding raised horny border that spreads centrifugally. Variants of porokeratosis have been described that differ in morphologic shape, distribution, and clinical course (Schamroth et al., 1997). However, as noted by Sybert (2010), the existence of several families with expression of more than one variant of porokeratosis among members, and individuals expressing more than one variant, suggest that the distinctions among these variants may be artificial. Disseminated superficial actinic porokeratosis (DSAP) is the most common subtype of porokeratosis.

Description Porokeratosis is a rare skin disorder characterized by one or more annular plaques with a surrounding raised horny border that spreads centrifugally. Variants of porokeratosis have been described that differ in morphologic shapes, distribution, and clinical course (Schamroth et al., 1997). However, as noted by Sybert (2010), several families with expression of more than one variant of porokeratosis among members as well as individuals expressing more than one variant have been reported, suggesting that the distinctions among these variants may be artificial. Disseminated superficial actinic porokeratosis (DSAP) is the most common subtype of porokeratosis. It is characterized by multiple small, annular, anhidrotic, keratotic lesions that are located predominantly on sun-exposed areas of the skin, such as the face, neck, and distal limbs.

Description Porokeratosis is a rare skin disorder characterized by one or more annular plaques with a surrounding raised horny border that spreads centrifugally. Variants of porokeratosis have been described that differ in morphologic shapes, distribution, and clinical course (Schamroth et al., 1997). However, as noted by Sybert (2010), reports of several families with expression of more than one variant of porokeratosis among members, and of individuals expressing more than one variant, suggest that the distinctions among these variants may be artificial. Disseminated superficial actinic porokeratosis (DSAP) is the most common subtype of porokeratosis. It is characterized by multiple small, annular, anhidrotic, keratotic lesions that are located predominantly on sun-exposed areas of the skin, such as the face, neck, and distal limbs.

Description Porokeratosis is a rare skin disorder characterized by one or more annular plaques with a surrounding raised horny border that spreads centrifugally. Variants of porokeratosis have been described that differ in morphologic shapes, distribution, and clinical course (Schamroth et al., 1997). However, as noted by Sybert (2010), several families with expression of more than one variant of porokeratosis among members, and individuals expressing more than one variant, have been reported, suggesting that the distinctions among these variants may be artificial. Disseminated superficial actinic porokeratosis (DSAP) is the most common subtype of porokeratosis. It is characterized by multiple small, annular, anhidrotic, keratotic lesions that are located predominantly on sun-exposed areas of the skin, such as the face, neck, and distal limbs.

Disseminated superficial actinic porokeratosis (DSAP) is a skin condition that causes dry, scaly patches. Symptoms include a large number of small, brownish patches with a distinctive border, found most commonly on sun-exposed areas of the skin (particularly the lower arms and legs). DSAP usually starts during the third or fourth decade of life and rarely affects children. Lesions generally are more prominent in the summer and less prominent in the winter. While DSAP is usually not cancerous, squamous cell carcinoma or Bowen’s disease may occasionally develop within patches.

Atypical Rett syndrome is a neurodevelopmental disorder that is diagnosed when a child has some of the symptoms of Rett syndrome but does not meet all the diagnostic criteria. Like the classic form of Rett syndrome, atypical Rett syndrome mostly affects girls. Children with atypical Rett syndrome can have symptoms that are either milder or more severe than those seen in Rett syndrome. Several subtypes of atypical Rett syndrome have been defined: The early-onset seizure type is characterized by seizures in the first months of life with later development of Rett features (including developmental problems, loss of language skills, and repeated hand wringing or hand washing movements). It is frequently caused by mutations in the X-linked CDKL5 gene (Xp22).

A number sign (#) is used with this entry because the congenital variant of Rett syndrome is caused by heterozygous mutation in the FOXG1 gene (164874) on chromosome 14q13. Description The congenital variant of Rett syndrome is a severe neurodevelopmental disorder with features of classic Rett syndrome (RTT; 312750), but earlier onset in the first months of life. Classic Rett syndrome shows later onset and is caused by mutation in the MECP2 gene (300005). Clinical Features Ariani et al. (2008) reported 2 unrelated girls, aged 22 years and 7 years, with a congenital variant of Rett syndrome. Both had normal birth, but developed progressive microcephaly at age 3 months.

All 29 patients had mutation in the MECP2 gene, of which 28 were missense (see, e.g., R133C; 312750.0001) or late truncating mutations. ... At age 1 year, he began to show stereotypic hand movements, bruxism, and constipation. At age 28 months, he presented severe global retardation and slight diffuse hypotonia. ... In the course of a systematic high-resolution chromosome analysis on 28 patients with Rett syndrome, Zoghbi et al. (1990) found a patient with a de novo balanced translocation t(X;3)(p22.1;q13.31).

Nemos et al. (2009) noted that this study brought the number of published CDKL5 mutations to 59, and indicated that CDKL5 mutations account for up to 28% of females with early-onset seizures and intractable epilepsy.

A rare genetic neurological disorder characterized by the presence of two or more of the main criteria for classic Rett syndrome (loss of acquired purposeful hand skills, loss of acquired spoken language, gait abnormalities, stereotypic hand movements), a period of regression followed by recovery or stabilization, and five out of eleven supportive criteria (breathing difficulties, bruxism, impaired sleep pattern, abnormal muscle tone, peripheral vasomotor disturbances, scoliosis/kyphosis, delayed growth, small cold hands and feet, inappropriate laughter or screaming spells, decreased pain sensation, and intense eye communication). Like classic Rett syndrome, it almost exclusively affects girls, while the disease course may be either milder or more severe. Epidemiology Based on reports that up to 32% of RTT cases show an atypical phenotype, the prevalence of atypical RTT is estimated at around 1/45,000. Like classic RTT, atypical RTT syndrome predominantly affects girls. Clinical description Atypical forms may present with either a milder or more severe clinical picture than that seen in typical RTT. Several subvariants of atypical RTT have been defined. i) The early-onset seizure type (Hanefeld variant) is characterized by seizures in the first months of life with subsequent development of RTT features. ii) The congenital variant (Rolando variant) is the most severe form of atypical RTT, with onset of classic RTT features during the first three months of life. iii) The 'forme fruste' is a milder variant with onset in early childhood and an incomplete and protracted course. iv) The late childhood regression form is characterized by a normal head circumference and by a more gradual and later onset (late childhood) regression of language and motor skills. v) The preserved speech variant (PSD or Zappella variant) is marked by recovery of some verbal and manual skills.

A number sign (#) is used with this entry because of evidence that early infantile epileptic encephalopathy-59 (EIEE59) is caused by heterozygous mutation in the GABBR2 gene (607340) on chromosome 9q22. For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350). Clinical Features The EuroEPINOMICS-RES Consortium et al. (2014) reported 2 unrelated patients, a 3-year-old girl (NLES8) and an 18-year-old man (NLES10), with EIEE59. The patients had onset of seizures within the first 3 months of life. The girl had multiple seizure types, whereas the male had infantile spasms that mostly resolved by age 5 months, although he had a few focal dyscognitive seizures and nonepileptic apneic spells later in life.

Reis-Bücklers corneal dystrophy (RBCD), also known as granular corneal dystrophy type III, is a rare form of superficial corneal dystrophy characterized by bilateral symmetrical reticular opacities in the superficial central cornea, with progressive visual impairment. Epidemiology Prevalence of this form of corneal dystrophy is not known. Clinical description Lesions develop at about 4 to 5 years of age. The opacities assume an irregular ring-shaped pattern of discrete spots and lines that focally elevate the corneal epithelium. RBCD remains asymptomatic until epithelial erosions precipitate acute episodes of ocular hyperemia, pain, and photophobia. Visual acuity eventually becomes reduced during the second and third decades of life following a progressive superficial haze and development of an irregular corneal surface.

Reis-Bücklers corneal dystrophy Other names Corneal dystrophy of Bowman layer, type I Reis-Bücklers corneal dystrophy. Reticular opacity in the superficial cornea Specialty Ophthalmology Reis-Bücklers corneal dystrophy , is a rare, corneal dystrophy of unknown cause, in which the Bowman's layer of the cornea undergoes disintegration. The disorder is inherited in an autosomal dominant fashion, and is associated with mutations in the gene TGFB1 . Reis-Bücklers dystrophy causes a cloudiness in the corneas of both eyes, which may occur as early as 1 year of age, but usually develops by 4 to 5 years of age. It is usually evident within the first decade of life. This cloudiness, or opacity, causes the corneal epithelium to become elevated, which leads to corneal opacities.

Distal spinal muscular atrophy type 3 is a rare neuromuscular disease characterized by progressive muscular weakness and atrophy predominantly affecting distal parts of limbs, later involvement of proximal and trunk muscles with marked hyperlordosis and late diaphragmatic dysfunction.

Multiple epiphyseal dysplasia type 5 is a multiple epiphyseal dysplasia characterized by an early-onset of pain and stiffness (involving knee and hip), progressive deformity of the extremities and precocious osteoarthritis associated with delayed and irregular ossification of epiphyses. Features specific to multiple epiphyseal dysplasia, type 5 include normal stature and lesser incidence of gait abnormalities. Radiographs reveal epiphyseal and metaphyseal irregularities. Multiple epiphyseal dysplasia type 5 follows an autosomal dominant mode of transmission.

Achondrogenesis is a group of severe disorders that are present from birth and affect the development of cartilage and bone. Infants with achondrogenesis usually have a small body, extremely short arms and legs, other skeletal abnormalities, and underdeveloped lungs. There are at least three forms of achondrogenesis, type 1A, type 1B and type 2. Achondrogenesis is usually diagnosed during pregnancy by ultrasound and genetic testing is used to distinguish between the three types. Type 1A and 1B achondrogenesis are both inherited in an autosomal recessive pattern.

A rare group of lethal skeletal dysplasias characterized by an endochondral ossification deficiency that leads to dwarfism with extreme micromelia, a small thorax, a prominent abdomen, anasarca and polyhydramnios. There are three types of achondrogenesis that exist and that differ clinically, radiologically, histologically and genetically: achondrogensis type 1a, type 1b and type 2.

Achondrogenesis Postmortem anteroposterior (A) and lateral (B) whole-body radiographs of the baby. Specialty Medical genetics Deaths Common Achondrogenesis is a number of disorders that are the most severe form of congenital chondrodysplasia (malformation of bones and cartilage ). These conditions are characterized by a small body, short limbs, and other skeletal abnormalities. As a result of their serious health problems, infants with achondrogenesis are usually born prematurely , are stillborn , or die shortly after birth from respiratory failure. Some infants, however, have lived for a while with intensive medical support.

A rare, systemic amyloidosis characterized by a triad of ophthalmologic, neurologic and dermatologic findings due to the deposition of gelsolin amyloid fibrils in these tissues. Clinical manifestations include corneal lattice dystrophy, cranial neuropathy, especially affecting the facial nerve, bulbar signs, cutis laxa, increased skin fragility, and less commonly peripheral neuropathy and renal failure.

Familial amyloidosis, Finnish type , or gelsolin amyloidosis, is a condition characterized by abnormal deposits of amyloid protein that mainly affect the eyes, nerves and skin. The 3 main features are amyloid deposits in the cornea ( corneal lattice dystrophy ), bilateral facial paralysis, and cutis laxa ("sagging" skin). Symptoms generally worsen with age. This condition is inherited in an autosomal dominant manner and is caused by mutations in the GSN gene. Treatment generally focuses on specific signs and symptoms. Plastic surgery may relieve problems caused by facial paralysis and cutis laxa.

A number sign (#) is used with this entry because the Finnish type of amyloidosis is caused by mutation in the gelsolin gene (GSN; 137350). See also corneal lattice dystrophy due to local amyloid deposition (122200), which occurs as an isolated dominant. Description The Finnish type of systemic amyloidosis is characterized clinically by a unique constellation of features including corneal lattice dystrophy, and cranial neuropathy, bulbar signs, and skin changes. Some patients may develop peripheral neuropathy and renal failure. The disorder is usually inherited in an autosomal dominant pattern; however, homozygotes with a more severe phenotype have also been reported (Meretoja, 1973). Clinical Features In a massive investigation in Finland, Meretoja (1973) identified 207 affected persons.

Lattice corneal dystrophy type II is characterized by an accumulation of protein clumps called amyloid deposits in tissues throughout the body. The deposits frequently occur in blood vessel walls and basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues. Amyloid deposits lead to characteristic signs and symptoms involving the eyes, nerves, and skin that worsen with age. The earliest sign of this condition, which is usually identified in a person's twenties, is accumulation of amyloid deposits in the cornea (lattice corneal dystrophy). The cornea is the clear, outer covering of the eye. It is made up of several layers of tissue, and in lattice corneal dystrophy type II, the amyloid deposits form in the stromal layer.

Hemoglobinopathy Toms River is a rare, genetic hemoglobinopathy disorder, due to a defect in the gama subunit of the fetal hemoglobin, characterized by neonatal cyanosis, low hemoglobin oxygen saturation levels without arterial hypoxemia, moderate anemia and reticulocytosis, not associated with heart or lung disease. Symptoms progressively subside within the first months of life.

A rare systemic autoimmune disease characterized by the presence of signs and symptoms suggestive of a systemic autoimmune disease that do not fulfil the existing classification criteria. The main clinical manifestations are arthritis with arthralgia, Raynaud's phenomenon, xerostomia, xerophthalmia, and leukopenia, while neurologic or renal involvement are virtually absent.