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Dominant hereditary optic atrophy(OPA1)

MedGen UID:
137902
Concept ID:
C0338508
Disease or Syndrome
Synonyms: Kjer-type optic atrophy; OPA1; Optic Atrophy Type 1; Optic Atrophy, Autosomal Dominant; Optic atrophy, juvenile
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Autosomal dominant optic atrophy (2065009); Autosomal dominant optic atrophy classic form (717336005); Autosomal dominant optic atrophy Kjer type (717336005); Kjer optic atrophy (717336005); Optic atrophy type 1 (717336005); Dominant hereditary optic atrophy (2065009)
 
Gene (location): OPA1 (3q29)
OMIM®: 165500
Orphanet: ORPHA98672

Disease characteristics

Excerpted from the GeneReview: Optic Atrophy Type 1
Optic atrophy type 1 (OPA1, or Kjer type optic atrophy) is characterized by bilateral and symmetric optic nerve pallor associated with insidious decrease in visual acuity (usually between ages 4 and 6 years), visual field defects, and color vision defects. Visual impairment is usually moderate (6/10 to 2/10), but ranges from mild or even insignificant to severe (legal blindness with acuity <1/20). The visual field defect is typically centrocecal, central, or paracentral; it is often large in those with severe disease. The color vision defect is often described as acquired blue-yellow loss (tritanopia). Other findings can include auditory neuropathy resulting in sensorineural hearing loss that ranges from severe and congenital to subclinical (i.e., identified by specific audiologic testing only). Visual evoked potentials are typically absent or delayed; pattern electroretinogram shows an abnormal N95:P50 ratio. Tritanopia is the classic feature of color vision defect, but more diffuse nonspecific dyschromatopsia is not uncommon. Ophthalmoscopic examination discloses temporal or diffuse pallor of the optic discs, sometimes associated with optic disc excavation. The neuroretinal rim shows some pallor in most cases, sometimes associated with a temporal pigmentary gray crescent. [from GeneReviews]
Authors:
Cécile Delettre-Cribaillet  |  Christian P Hamel  |  Guy Lenaers   view full author information

Additional descriptions

From OMIM
Autosomal dominant optic atrophy is characterized by an insidious onset of visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disc pallor, color vision deficits, and centrocecal scotoma of variable density (Votruba et al., 1998). Some patients with mutations in the OPA1 gene may also develop extraocular neurologic features, such as deafness, progressive external ophthalmoplegia, muscle cramps, hyperreflexia, and ataxia; see 125250. There appears to be a wide range of intermediate phenotypes (Yu-Wai-Man et al., 2010). Yu-Wai-Man et al. (2009) provided a detailed review of autosomal dominant optic atrophy and Leber hereditary optic neuropathy (LHON; 535000), with emphasis on the selective vulnerability of retinal ganglion cells to mitochondrial dysfunction in both disorders. Genetic Heterogeneity of Optic Atrophy Optic atrophy-2 (OPA2; 311050) maps to chromosome Xp11.4-p11.21. OPA3 (165300) is caused by mutation in the OPA3 gene (606580) on chromosome 19q13. OPA4 (605293) maps to chromosome 18q12.2-q12.3. OPA5 (610708) maps to chromosome 22q12.1-q13.1. OPA6 (258500) maps to chromosome 8q. OPA7 (612989) is caused by mutation in the TMEM126A gene (612988) on chromosome 11q14. OPA8 (616648) maps to chromosome 16q21-q22. OPA9 (616289) is caused by mutation in the ACO2 gene (100850) on chromosome 22q13; OPA10 (616732) is caused by mutation in the RTN4IP1 gene (610502) on chromosome 6q21; and OPA11 (617302) is caused by mutation in the YME1L1 gene (607472) on chromosome 10p12.  http://www.omim.org/entry/165500
From GHR
Optic atrophy type 1 is a condition that affects vision. Individuals with this condition have progressive vision loss that typically begins within the first decade of life. The severity of the vision loss varies widely among affected people, even among members of the same family. People with this condition can range from having nearly normal vision to complete blindness. The vision loss usually progresses slowly.People with optic atrophy type 1 frequently have problems with color vision that make it difficult or impossible to distinguish between shades of blue and green. Other vision problems associated with this condition include a progressive narrowing of the field of vision (tunnel vision) and an abnormally pale appearance (pallor) of the nerve that relays visual information from the eye to the brain (optic nerve). Optic nerve pallor can be detected during an eye examination.  https://ghr.nlm.nih.gov/condition/optic-atrophy-type-1

Clinical features

Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
Strabismus (also known as squint) is a condition in which the eyes are not properly aligned with each other.
Central scotoma
MedGen UID:
57750
Concept ID:
C0152191
Finding
An area of depressed vision located at the point of fixation and that interferes with central vision.
Progressive external ophthalmoplegia
MedGen UID:
102439
Concept ID:
C0162674
Disease or Syndrome
Progressive external ophthalmoplegia is a condition characterized by weakness of the eye muscles. The condition typically appears in adults between ages 18 and 40 and slowly worsens over time. The first sign of progressive external ophthalmoplegia is typically drooping eyelids (ptosis), which can affect one or both eyelids. As ptosis worsens, affected individuals may use the forehead muscles to try to lift the eyelids, or they may lift up their chin in order to see. Another characteristic feature of progressive external ophthalmoplegia is weakness or paralysis of the muscles that move the eye (ophthalmoplegia). Affected individuals have to turn their head to see in different directions, especially as the ophthalmoplegia worsens. People with progressive external ophthalmoplegia may also have general weakness of the muscles used for movement (myopathy), particularly those in the neck, arms, or legs. The weakness may be especially noticeable during exercise (exercise intolerance). Muscle weakness may also cause difficulty swallowing (dysphagia).When the muscle cells of affected individuals are stained and viewed under a microscope, these cells usually appear abnormal. These abnormal muscle cells contain an excess of cell structures called mitochondria and are known as ragged-red fibers.Although muscle weakness is the primary symptom of progressive external ophthalmoplegia, this condition can be accompanied by other signs and symptoms. In these instances, the condition is referred to as progressive external ophthalmoplegia plus (PEO+). Additional signs and symptoms can include hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss), weakness and loss of sensation in the limbs due to nerve damage (neuropathy), impaired muscle coordination (ataxia), a pattern of movement abnormalities known as parkinsonism, and depression.Progressive external ophthalmoplegia is part of a spectrum of disorders with overlapping signs and symptoms. Similar disorders include ataxia neuropathy spectrum and Kearns-Sayre syndrome. Like progressive external ophthalmoplegia, the other conditions in this spectrum can involve weakness of the eye muscles. However, these conditions have many additional features not shared by most people with progressive external ophthalmoplegia.
Centrocecal scotoma
MedGen UID:
82870
Concept ID:
C0271196
Finding
A scotoma (area of diminished vision within the visual field) located between the central point of fixation and the blind spot with a roughly horizontal oval shape.
Horizontal nystagmus
MedGen UID:
124399
Concept ID:
C0271385
Disease or Syndrome
Nystagmus consisting of horizontal to-and-fro eye movements.
Tritanomaly
MedGen UID:
370841
Concept ID:
C1970167
Finding
Difficulty distinguishing between yellow and blue, possible related to dysfunction of the S photopigment.
Red-green dyschromatopsia
MedGen UID:
410005
Concept ID:
C1970168
Finding
Difficulty with discriminating red and green hues.
Reduced visual acuity
MedGen UID:
461148
Concept ID:
C3149798
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.
Abnormal amplitude of pattern reversal visual evoked potentials
MedGen UID:
871342
Concept ID:
C4025834
Finding
Ataxia
MedGen UID:
849
Concept ID:
C0007758
Sign or Symptom
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Proximal muscle weakness
MedGen UID:
325534
Concept ID:
C1838869
Sign or Symptom
A lack of strength of the proximal muscles.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDominant hereditary optic atrophy
Follow this link to review classifications for Dominant hereditary optic atrophy in Orphanet.

Recent clinical studies

Diagnosis

Skidd PM, Lessell S, Cestari DM
Semin Ophthalmol 2013 Sep-Nov;28(5-6):422-6. doi: 10.3109/08820538.2013.825296. PMID: 24138050

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