Autosomal dominant optic atrophy

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Classification according to ICD-10
H47.2 Optic atrophy
ICD-10 online (WHO version 2019)

The autosomal dominant optic atrophy ( ADOA ), English autosomal dominant optic atrophy is a group of rare congenital diseases with the main features of an optic atrophy .

ADOA are the most common forms of hereditary neuropathy of the optic nerve , along with Leber's optic neuropathy (LHON) . It is based on the degeneration of ganglion cells in the retina .

Classification

This group of diseases includes the following diseases:

  • DOA + Optic atrophy plus syndrome (synonym: Hagemoser-Weinstein Bresnick syndrome , optic atrophy - deafness polyneuropathy - myopathy), autosomal dominant , with mutations at OPA1 - gene in chromosome 3 locus q29
  • OPA1 optic atrophy, type OPA1, (synonym: autosomal dominant optic atrophy type Kjer; optic atrophy type 1; optic atrophy type Kjer), autosomal dominant, mutations in the OPA1 gene
  • OPA2 , (synonym: optic atrophy (not liver type) with early onset; optic atrophy type 2), X-linked recessive , mutations in the X-chromosome locus p11.4-p11.21
  • OPA3 , autosomal dominant, mutations in the OPA3 gene in chromosome 19 locus q13.32 s. also Costeff syndrome
  • OPA4 , mutations in chromosome 18 q12.2-q12.3
  • OPA5 , autosomal dominant, mutations in chromosome 22 q12.1-q13.1
  • OPA6 (synonyms: optic atrophy, autosomal recessive, isolated; optic atrophy, congenital or early infantile), autosomal recessive, mutations in chromosome 8 q21-q22
  • OPA7 , autosomal recessive, mutations in the TMEM126A gene in chromosome 11 q14.1

Clinical manifestations

With all diseases, the loss of vision begins in childhood or adolescence. Usually there are other affected persons in the family. The ophthalmoscope shows a pale papilla on both sides with a central loss of visual acuity and color vision.

Differential diagnosis

ADOA and Leber hereditary optic neuropathy (LHON) are distinguishable, rare mitochondrial diseases . However, they are clinically as well as pathogenetically similar in certain aspects . In these hereditary optic neuropathies, retinal ganglion cells are destroyed . In LHON, the mitochondrial defect is related to a mutation in the mitochondrial DNA , in ADOA to a defect in the somatic DNA. Both diseases result from a mitochondrial complex I defect. For example, B. Barboni et al. (2013) on the pathogenetic relationship of LHON and ADOA. Affected patients usually suffer from central vision loss and color vision disorders.

The clinical symptoms of ADOA are mostly limited to optic neuropathy. The severity ranges from severe congenital optical atrophy to relatively mild cases. As with LHON, vision loss in ADOA affects central vision with central scotoma and loss of color contrast vision. The temporal side of the papilla is particularly impaired, as the papillomacular bundle is affected at an early stage. ADOA usually progresses slowly without spontaneous improvement.

therapy

No causal treatment is known. A idebenone therapy has been used successfully in ADOA / OPA-1 by specialists from Milan in individual cases. The results of this open, uncontrolled clinical study on idebenone in 7 patients with OPA1-associated ADOA were published in 2013 (Barboni 2013). Regarding the results described, La Morgia et al. (2014) state that spontaneous improvements in ADOA have not yet become known, and the results of Barboni et al. (2013) are therefore encouraging. Barboni et al. (2013) advocate the use of idebenone in ADOA patients based on the results of their pilot study (5 out of 7 patients benefited from idebenone therapy). They advocate the implementation of further randomized and controlled clinical trials.

literature

  • P. Barboni et al .: Idebenone treatment in patients with OPA1-mutant dominant optic atrophy . In: Brain - A Journal of Neurology . February 1, 2013, doi : 10.1093 / brain / aws280 .
  • P. Barboni et al .: Medical Management of Hereditary Optic Neuropathies . In: frontiers in Neurology . July 31, 2014, doi : 10.3389 / fneur.2014.00141 .

Web links

Individual evidence

  1. ↑ Optic atrophy, autosomal dominant. In: Orphanet (Rare Disease Database).
  2. ↑ a b Medical Genetic Center
  3. ↑ Optic atrophy plus syndrome, autosomal dominant. In: Orphanet (Rare Disease Database).
  4. ↑ Optic atrophy plus syndrome.  In: Online Mendelian Inheritance in Man . (English)
  5. ↑ autosomal dominant optic atrophy.  In: Online Mendelian Inheritance in Man . (English)
  6. ↑ Optic atrophy, type OPA1. In: Orphanet (Rare Disease Database).
  7. ^ Optic atrophy 1.  In: Online Mendelian Inheritance in Man . (English)
  8. ↑ Optic atrophy, X-linked, with early onset. In: Orphanet (Rare Disease Database).
  9. ↑ Optic atrophy 2, X-linked.  In: Online Mendelian Inheritance in Man . (English)
  10. ↑ Optic atrophy and cataract, autosomal dominant form. In: Orphanet (Rare Disease Database).
  11. ^ Optic atrophy 3 with cataract.  In: Online Mendelian Inheritance in Man . (English)
  12. ^ Optic atrophy 4th  In: Online Mendelian Inheritance in Man . (English)
  13. ^ Optic atrophy 5.  In: Online Mendelian Inheritance in Man . (English)
  14. ↑ Optic atrophy, autosomal recessive, type 6. In: Orphanet (database for rare diseases).
  15. ^ Optic atrophy 6.  In: Online Mendelian Inheritance in Man . (English)
  16. ↑ Optic atrophy, autosomal recessive, type 7. In: Orphanet (database for rare diseases).
  17. ^ Optic atrophy 7.  In: Online Mendelian Inheritance in Man . (English)
  18. ↑ a b Idebenone treatment in patients with OPA1-mutant dominant optic atrophy
  19. ^ Medical Management of Hereditary Optic Neuropathies . PMC 4117178 (free full text)