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Optic atrophy 11(OPA11)

MedGen UID:
934595
Concept ID:
C4310628
Disease or Syndrome
Synonym: OPA11
 
Gene (location): YME1L1 (10p12.1)
 
Monarch Initiative: MONDO:0015011
OMIM®: 617302

Definition

OPA11 is an autosomal recessive disorder characterized by delayed psychomotor development, intellectual disability, ataxia, optic atrophy, and leukoencephalopathy on brain imaging. Laboratory studies are consistent with mitochondrial dysfunction (summary by Hartmann et al., 2016). For a discussion of genetic heterogeneity of optic atrophy, see OPA1 (165500). [from OMIM]

Clinical features

From HPO
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Macrotia
MedGen UID:
488785
Concept ID:
C0152421
Congenital Abnormality
Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective).
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
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- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Leukoencephalopathy
MedGen UID:
78722
Concept ID:
C0270612
Disease or Syndrome
This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells.
Hyperactivity
MedGen UID:
98406
Concept ID:
C0424295
Finding
Hyperactivity is a state of constantly being unusually or abnormally active, including in situations in which it is not appropriate.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Hyperkinetic movements
MedGen UID:
854367
Concept ID:
C3887506
Disease or Syndrome
Motor hyperactivity with excessive movement of muscles of the body as a whole.
Brain atrophy
MedGen UID:
1643639
Concept ID:
C4551584
Disease or Syndrome
Partial or complete wasting (loss) of brain tissue that was once present.
Facial diplegia
MedGen UID:
322796
Concept ID:
C1836003
Finding
Facial diplegia refers to bilateral facial palsy (bilateral facial palsy is much rarer than unilateral facial palsy).
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Amblyopia
MedGen UID:
8009
Concept ID:
C0002418
Disease or Syndrome
Reduced visual acuity that is uncorrectable by lenses in the absence of detectable anatomic defects in the eye or visual pathways.
Hypermetropia
MedGen UID:
43780
Concept ID:
C0020490
Disease or Syndrome
An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry.
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.
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
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
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.

Professional guidelines

PubMed

Ferro Desideri L, Traverso CE, Iester M
Drugs Today (Barc) 2022 Nov;58(11):547-552. doi: 10.1358/dot.2022.58.11.3448291. PMID: 36422516
Pan KS, FitzGibbon EJ, Vitale S, Lee JS, Collins MT, Boyce AM
J Bone Miner Res 2020 Nov;35(11):2199-2210. Epub 2020 Aug 24 doi: 10.1002/jbmr.4129. PMID: 32644197
Chen AT, Brady L, Bulman DE, Sundaram ANE, Rodriguez AR, Margolin E, Waye JS, Tarnopolsky MA
PLoS One 2019;14(11):e0225656. Epub 2019 Nov 25 doi: 10.1371/journal.pone.0225656. PMID: 31765440Free PMC Article

Recent clinical studies

Etiology

Rocatcher A, Desquiret-Dumas V, Charif M, Ferré M, Gohier P, Mirebeau-Prunier D, Verny C, Milea D, Lenaers G; HON Collaborators Group, Bonneau D, Reynier P, Amati-Bonneau P
Brain 2023 Feb 13;146(2):455-460. doi: 10.1093/brain/awac395. PMID: 36317462
Hanna Al-Shaikh R, Milanowski LM, Holla VV, Kurihara K, Yadav R, Kamble N, Muthusamy B, Bellad A, Koziorowski D, Szlufik S, Hoffman-Zacharska D, Fujioka S, Tsuboi Y, Ross OA, Wierenga K, Uitti RJ, Wszolek Z, Pal PK
Parkinsonism Relat Disord 2022 Aug;101:66-74. Epub 2022 Jun 30 doi: 10.1016/j.parkreldis.2022.06.016. PMID: 35803092
Akgun A, Sen A, Onal H
J Pediatr Endocrinol Metab 2021 Nov 25;34(11):1425-1433. Epub 2021 Aug 26 doi: 10.1515/jpem-2021-0242. PMID: 34448386
Newman NJ, Yu-Wai-Man P, Carelli V, Moster ML, Biousse V, Vignal-Clermont C, Sergott RC, Klopstock T, Sadun AA, Barboni P, DeBusk AA, Girmens JF, Rudolph G, Karanjia R, Taiel M, Blouin L, Smits G, Katz B, Sahel JA; LHON Study Group
Ophthalmology 2021 May;128(5):649-660. Epub 2021 Jan 12 doi: 10.1016/j.ophtha.2020.12.012. PMID: 33451738
Rizvi R, Anjum Q
J Pak Med Assoc 2005 Nov;55(11):502-7. PMID: 16304873

Diagnosis

Rocatcher A, Desquiret-Dumas V, Charif M, Ferré M, Gohier P, Mirebeau-Prunier D, Verny C, Milea D, Lenaers G; HON Collaborators Group, Bonneau D, Reynier P, Amati-Bonneau P
Brain 2023 Feb 13;146(2):455-460. doi: 10.1093/brain/awac395. PMID: 36317462
Ferro Desideri L, Traverso CE, Iester M
Drugs Today (Barc) 2022 Nov;58(11):547-552. doi: 10.1358/dot.2022.58.11.3448291. PMID: 36422516
Azad R, Sinha S, Nishant P
Indian J Ophthalmol 2021 Nov;69(11):3026-3034. doi: 10.4103/ijo.IJO_1525_21. PMID: 34708738Free PMC Article
Akgun A, Sen A, Onal H
J Pediatr Endocrinol Metab 2021 Nov 25;34(11):1425-1433. Epub 2021 Aug 26 doi: 10.1515/jpem-2021-0242. PMID: 34448386
Newman NJ, Yu-Wai-Man P, Carelli V, Moster ML, Biousse V, Vignal-Clermont C, Sergott RC, Klopstock T, Sadun AA, Barboni P, DeBusk AA, Girmens JF, Rudolph G, Karanjia R, Taiel M, Blouin L, Smits G, Katz B, Sahel JA; LHON Study Group
Ophthalmology 2021 May;128(5):649-660. Epub 2021 Jan 12 doi: 10.1016/j.ophtha.2020.12.012. PMID: 33451738

Therapy

Lam BL, Feuer WJ, Davis JL, Porciatti V, Yu H, Levy RB, Vanner E, Guy J
Am J Ophthalmol 2022 Sep;241:262-271. Epub 2022 Mar 7 doi: 10.1016/j.ajo.2022.02.023. PMID: 35271811Free PMC Article
Newman NJ, Yu-Wai-Man P, Carelli V, Moster ML, Biousse V, Vignal-Clermont C, Sergott RC, Klopstock T, Sadun AA, Barboni P, DeBusk AA, Girmens JF, Rudolph G, Karanjia R, Taiel M, Blouin L, Smits G, Katz B, Sahel JA; LHON Study Group
Ophthalmology 2021 May;128(5):649-660. Epub 2021 Jan 12 doi: 10.1016/j.ophtha.2020.12.012. PMID: 33451738
Law SK, Wang L, Li T
Cochrane Database Syst Rev 2020 Feb 7;2(2):CD006030. doi: 10.1002/14651858.CD006030.pub4. PMID: 32032457Free PMC Article
Schmitt HM, Schlamp CL, Nickells RW
Neurosci Lett 2016 Jun 20;625:11-5. Epub 2015 Dec 28 doi: 10.1016/j.neulet.2015.12.012. PMID: 26733303Free PMC Article
Law SK, Li T
Cochrane Database Syst Rev 2013 May 31;5(5):CD006030. doi: 10.1002/14651858.CD006030.pub3. PMID: 23728656Free PMC Article

Prognosis

Ferro Desideri L, Traverso CE, Iester M
Drugs Today (Barc) 2022 Nov;58(11):547-552. doi: 10.1358/dot.2022.58.11.3448291. PMID: 36422516
Newman NJ, Yu-Wai-Man P, Carelli V, Moster ML, Biousse V, Vignal-Clermont C, Sergott RC, Klopstock T, Sadun AA, Barboni P, DeBusk AA, Girmens JF, Rudolph G, Karanjia R, Taiel M, Blouin L, Smits G, Katz B, Sahel JA; LHON Study Group
Ophthalmology 2021 May;128(5):649-660. Epub 2021 Jan 12 doi: 10.1016/j.ophtha.2020.12.012. PMID: 33451738
Armangue T, Olivé-Cirera G, Martínez-Hernandez E, Sepulveda M, Ruiz-Garcia R, Muñoz-Batista M, Ariño H, González-Álvarez V, Felipe-Rucián A, Jesús Martínez-González M, Cantarín-Extremera V, Concepción Miranda-Herrero M, Monge-Galindo L, Tomás-Vila M, Miravet E, Málaga I, Arrambide G, Auger C, Tintoré M, Montalban X, Vanderver A, Graus F, Saiz A, Dalmau J; Spanish Pediatric anti-MOG Study Group
Lancet Neurol 2020 Mar;19(3):234-246. Epub 2020 Feb 10 doi: 10.1016/S1474-4422(19)30488-0. PMID: 32057303
Ohno-Matsui K, Lai TY, Lai CC, Cheung CM
Prog Retin Eye Res 2016 May;52:156-87. Epub 2016 Jan 6 doi: 10.1016/j.preteyeres.2015.12.001. PMID: 26769165
Finsterer J
Eur J Neurol 2004 Mar;11(3):163-86. doi: 10.1046/j.1351-5101.2003.00728.x. PMID: 15009163

Clinical prediction guides

Costa CBDC, Freitas D
Int Ophthalmol 2022 Oct;42(10):3117-3127. Epub 2022 May 15 doi: 10.1007/s10792-022-02311-8. PMID: 35569052
Azad R, Sinha S, Nishant P
Indian J Ophthalmol 2021 Nov;69(11):3026-3034. doi: 10.4103/ijo.IJO_1525_21. PMID: 34708738Free PMC Article
Armangue T, Olivé-Cirera G, Martínez-Hernandez E, Sepulveda M, Ruiz-Garcia R, Muñoz-Batista M, Ariño H, González-Álvarez V, Felipe-Rucián A, Jesús Martínez-González M, Cantarín-Extremera V, Concepción Miranda-Herrero M, Monge-Galindo L, Tomás-Vila M, Miravet E, Málaga I, Arrambide G, Auger C, Tintoré M, Montalban X, Vanderver A, Graus F, Saiz A, Dalmau J; Spanish Pediatric anti-MOG Study Group
Lancet Neurol 2020 Mar;19(3):234-246. Epub 2020 Feb 10 doi: 10.1016/S1474-4422(19)30488-0. PMID: 32057303
Ohno-Matsui K, Lai TY, Lai CC, Cheung CM
Prog Retin Eye Res 2016 May;52:156-87. Epub 2016 Jan 6 doi: 10.1016/j.preteyeres.2015.12.001. PMID: 26769165
Polletta L, Vernucci E, Carnevale I, Arcangeli T, Rotili D, Palmerio S, Steegborn C, Nowak T, Schutkowski M, Pellegrini L, Sansone L, Villanova L, Runci A, Pucci B, Morgante E, Fini M, Mai A, Russo MA, Tafani M
Autophagy 2015;11(2):253-70. doi: 10.1080/15548627.2015.1009778. PMID: 25700560Free PMC Article

Recent systematic reviews

Dulski J, Souza J, Santos ML, Wszolek ZK
Orphanet J Rare Dis 2023 Jun 22;18(1):160. doi: 10.1186/s13023-023-02772-9. PMID: 37349768Free PMC Article
Garzón-Rodríguez MC, Reyes-Figueredo LS, Velandia-Rodríguez LÁ, Méndez-Ruiz OD, Gómez-Rodríguez MA, Esguerra-Ochoa LT, García-Lozada D
Arch Soc Esp Oftalmol (Engl Ed) 2023 Feb;98(2):83-97. Epub 2022 Sep 6 doi: 10.1016/j.oftale.2022.06.016. PMID: 36068132
Law SK, Wang L, Li T
Cochrane Database Syst Rev 2020 Feb 7;2(2):CD006030. doi: 10.1002/14651858.CD006030.pub4. PMID: 32032457Free PMC Article
Gharaibeh A, Savage HI, Scherer RW, Goldberg MF, Lindsley K
Cochrane Database Syst Rev 2013 Dec 3;12(12):CD005431. doi: 10.1002/14651858.CD005431.pub3. PMID: 24302299Free PMC Article
Law SK, Li T
Cochrane Database Syst Rev 2013 May 31;5(5):CD006030. doi: 10.1002/14651858.CD006030.pub3. PMID: 23728656Free PMC Article

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