brief presentation on autosomal dominant optic atrophy

1. AUTOSOMAL
DOMINANT OPTIC
ATROPHY
-GERSHON HAYFORD-

2. CLASSIFICATION AND EXTERNAL
RESOURCES
An autosomal inherited disease that
affects the optic nerves, causing
reduced visual acuity and
blindness beginning in childhood.
This condition is due to
mitochondrial dysfunction
mediating the death of optic nerve
fibres.

3. First described clinically by BATTEN
in 1896 and named Kjer’s Optic
Neuropathy in 1959 after Danish
ophthalmologist POUL KJER, who
studied 19 families with the disease
Synonyms
Kjer’s Optic nueropathy
Kjer’s optic atrophy
Kjer’s autosomal optic atrophy

4. HOW IS DOA PRESENTED?
 Presented as an isolated bilateral optic
neuropathy (non-syndromic form) or rather as
a complicated phenotype with extra-ocular
signs (syndromic form)
 Changes in VISION
 Loss of Visual Acuity-Progressive pattern of
vision loss beginning in childhood and is hence a
contributor to childhood blindness
 Scotomas-In the central visual fields with
peripheral vision.
 Colour blindness

5. CONTINUED….
 Changes in FUNDUS
 Temporal Pallor (indicating atrophy)
 Excavation of the optic disc, as is also seen in
Leber hereditary optic neuropathy
 Normal tension glaucoma
 *peripheral neuropathy, deafness, cerebellar
ataxia, spastic paraparesis, myopathy*

8. INCIDENCE AND INHERITANCE
Incidence- Estimated as 1:50000 with
high penetrance of 98%
Prevalence as high as 1:10000 in the
Danish population (Votruba, 1998)
Is inherited in an autosomal dominant
manner
Males and females are affected at the
same rate

9. PATHOPHYSIOLOGY
 Mutation of the OPA1 gene found on chromosome 3,
region q28-qter. The OPA1 gene codes for a dynamin-
related GTPase protein.
 FUNCTIONS OF OPA1 gene
 Organization of the shape and structure of the
mitochondria and apoptosis, oxidative
phosphorylation and maintenance of the small
amount of DNA within mitochondria, called
mitochondrial DNA (mtDNA).
 Also, 5 other chromosomal genes are described as
causing optic atrophy:
 OPA2 (x-linked), OPA3 (dominant), OPA4 (dominant),
OPA5 (dominant) and OPA6 (recessive)

11. MANAGEMENT
To date, there is no preventative or
curative treatment in DOA; severely
visually impaired patients may benefit
from low vision aids. Genetic counseling
is commonly offered and patients are
advised to avoid alcohol and tobacco
consumption, as well as the use of
medications that may interfere with
mitochondrial metabolism. Gene and
pharmacological therapies for DOA are
currently under investigation

12. REFERENCES
 Kjer B, Eiberg H, Kjer P, Rosenberg T. “Dominant optic atrophy
mapped to chromosome 3q region. II. Clinical and epidemiological
aspects”. Acta Ophthalmol Scand. 1996;74(1):3-7.
 Votruba M, Fitzke FW, Holder CE, Carter A, Bhattacharya SS, Moore
AT. “Clinical features in affected individuals from 21 pedigrees with
dominant optic atrophy”. Arch Ophthalmol. 1998;116(3):353-358.
 Delettre C, Lenaers G, Pelloquin L, Belenguer P, Hamel CP. “OPA1
(Kjer type) dominant optic atrophy: a novel mitochondrial disease”.
Mol Genet Metab. 2002;75(2):97-107.
 Kline LB, Glaser JS. Dominant optic atrophy: The clinical profile.
Arch Ophthalmol. 1979;97(9):245-251.
 Newman NJ. “Hereditary Optic Neuropathies: from the mitochondria
to the optic nerve”. Am J Ophthal. 2005;140(3):517-523.
 Carelli V, La Morgia C, Sadun AA. “Mitochondrial dysfunction in optic
neuropathies: animal models and therapeutic options”. Curr Opin
Neurol. 2013;26(1):52-58.

13. THANK YOU FOR YOUR ATTENTION
Our greatest weakness lies in
giving up. The most certain way
to succeed is always to try one
more time. Thomas A Edison

14. QUESTIONS TIME