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Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy(DOA+)

MedGen UID:
478179
Concept ID:
C3276549
Disease or Syndrome
Synonyms: DOA+; DOMINANT OPTIC ATROPHY PLUS SYNDROME; OPTIC ATROPHY WITH OR WITHOUT DEAFNESS, OPHTHALMOPLEGIA, MYOPATHY, ATAXIA, AND NEUROPATHY
SNOMED CT: Autosomal dominant optic atrophy plus syndrome (715374003); ADOA (autosomal dominant optic atrophy) plus (715374003)
 
Gene (location): OPA1 (3q29)
 
Monarch Initiative: MONDO:0007429
OMIM®: 125250

Definition

Syndromic optic atrophy, also known as DOA+ syndrome, is a neurologic disorder characterized most commonly by an insidious onset of visual loss and sensorineural hearing loss in childhood with variable presentation of other clinical manifestations including progressive external ophthalmoplegia (PEO), muscle cramps, hyperreflexia, and ataxia. There appears to be a wide range of intermediate phenotypes (Yu-Wai-Man et al., 2010). [from OMIM]

Clinical features

From HPO
Progressive sensorineural hearing impairment
MedGen UID:
335894
Concept ID:
C1843156
Disease or Syndrome
A progressive form of sensorineural hearing impairment.
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).
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
Polyneuropathy
MedGen UID:
57502
Concept ID:
C0152025
Disease or Syndrome
A generalized disorder of peripheral nerves.
Abnormal auditory evoked potentials
MedGen UID:
141758
Concept ID:
C0522216
Finding
An abnormality of the auditory evoked potentials, which are used to trace the signal generated by a sound, from the cochlear nerve, through the lateral lemniscus, to the medial geniculate nucleus, and to the cortex.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk. In general, this can refer to neurological diseases but also fractures or other sources of pain that is triggered upon walking. However, in the current context gait disturbance refers to difficulty walking on the basis of a neurological or muscular disease.
Abnormal amplitude of pattern reversal visual evoked potentials
MedGen UID:
871342
Concept ID:
C4025834
Finding
Myopathy
MedGen UID:
10135
Concept ID:
C0026848
Disease or Syndrome
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
Increased variability in muscle fiber diameter
MedGen UID:
336019
Concept ID:
C1843700
Finding
An abnormally high degree of muscle fiber size variation. This phenotypic feature can be observed upon muscle biopsy.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Ophthalmoplegia
MedGen UID:
45205
Concept ID:
C0029089
Sign or Symptom
Paralysis of one or more extraocular muscles that are responsible for eye movements.
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.
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.
Red-green dyschromatopsia
MedGen UID:
102324
Concept ID:
C0155016
Disease or Syndrome
Difficulty with discriminating red and green hues.
Blue color blindness
MedGen UID:
57827
Concept ID:
C0155017
Disease or Syndrome
Tritanopia is an autosomal dominant disorder of human vision characterized by a selective deficiency of blue spectral sensitivity (Weitz et al., 1992).
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
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.
Dyschromatopsia
MedGen UID:
163559
Concept ID:
C0858618
Disease or Syndrome
A form of colorblindness in which only two of the three fundamental colors can be distinguished due to a lack of one of the retinal cone pigments.
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Bennett JL, Costello F, Chen JJ, Petzold A, Biousse V, Newman NJ, Galetta SL
Lancet Neurol 2023 Jan;22(1):89-100. Epub 2022 Sep 22 doi: 10.1016/S1474-4422(22)00187-9. PMID: 36155661
Urano F
Curr Diab Rep 2016 Jan;16(1):6. doi: 10.1007/s11892-015-0702-6. PMID: 26742931Free PMC Article
Karaa A, Goldstein A
Pediatr Diabetes 2015 Feb;16(1):1-9. Epub 2014 Oct 20 doi: 10.1111/pedi.12223. PMID: 25330715

Recent clinical studies

Etiology

Cartes-Saavedra B, Lagos D, Macuada J, Arancibia D, Burté F, Sjöberg-Herrera MK, Andrés ME, Horvath R, Yu-Wai-Man P, Hajnóczky G, Eisner V
Proc Natl Acad Sci U S A 2023 Mar 21;120(12):e2207471120. Epub 2023 Mar 16 doi: 10.1073/pnas.2207471120. PMID: 36927155Free PMC Article
Newman NJ, Yu-Wai-Man P, Subramanian PS, Moster ML, Wang AG, Donahue SP, Leroy BP, Carelli V, Biousse V, Vignal-Clermont C, Sergott RC, Sadun AA, Rebolleda Fernández G, Chwalisz BK, Banik R, Bazin F, Roux M, Cox ED, Taiel M, Sahel JA; LHON REFLECT Study Group
Brain 2023 Apr 19;146(4):1328-1341. doi: 10.1093/brain/awac421. PMID: 36350566Free PMC Article
Davila-Siliezar P, Carter M, Milea D, Lee AG
Curr Opin Ophthalmol 2022 Nov 1;33(6):574-578. Epub 2022 Aug 24 doi: 10.1097/ICU.0000000000000891. PMID: 36066375
Meunier I, Bocquet B, Defoort-Dhellemmes S, Smirnov V, Arndt C, Picot MC, Dollfus H, Charif M, Audo I, Huguet H, Zanlonghi X, Lenaers G
Sci Rep 2021 Sep 21;11(1):18703. doi: 10.1038/s41598-021-98150-1. PMID: 34548540Free PMC Article
Dul MW
Optom Clin 1993;3(2):91-101. PMID: 8268699

Diagnosis

Carelli V, La Morgia C, Yu-Wai-Man P
Handb Clin Neurol 2023;194:23-42. doi: 10.1016/B978-0-12-821751-1.00010-5. PMID: 36813316
Rigoli L, Caruso V, Salzano G, Lombardo F
Int J Environ Res Public Health 2022 Mar 9;19(6) doi: 10.3390/ijerph19063225. PMID: 35328914Free PMC Article
Banc A, Bianchi Marzoli S
Eur J Ophthalmol 2022 Jan;32(1):95-101. Epub 2021 Nov 11 doi: 10.1177/11206721211060655. PMID: 34761686
Sundaramurthy S, SelvaKumar A, Ching J, Dharani V, Sarangapani S, Yu-Wai-Man P
Graefes Arch Clin Exp Ophthalmol 2021 Sep;259(9):2461-2472. Epub 2020 Nov 13 doi: 10.1007/s00417-020-04993-1. PMID: 33185731
Lenaers G, Hamel C, Delettre C, Amati-Bonneau P, Procaccio V, Bonneau D, Reynier P, Milea D
Orphanet J Rare Dis 2012 Jul 9;7:46. doi: 10.1186/1750-1172-7-46. PMID: 22776096Free PMC Article

Therapy

Shamsnajafabadi H, MacLaren RE, Cehajic-Kapetanovic J
Cells 2023 Aug 7;12(15) doi: 10.3390/cells12152013. PMID: 37566092Free PMC Article
Gorgogietas V, Rajaei B, Heeyoung C, Santacreu BJ, Marín-Cañas S, Salpea P, Sawatani T, Musuaya A, Arroyo MN, Moreno-Castro C, Benabdallah K, Demarez C, Toivonen S, Cosentino C, Pachera N, Lytrivi M, Cai Y, Carnel L, Brown C, Urano F, Marchetti P, Gilon P, Eizirik DL, Cnop M, Igoillo-Esteve M
Diabetologia 2023 Jul;66(7):1306-1321. Epub 2023 Mar 30 doi: 10.1007/s00125-023-05905-8. PMID: 36995380Free PMC Article
Newman NJ, Yu-Wai-Man P, Subramanian PS, Moster ML, Wang AG, Donahue SP, Leroy BP, Carelli V, Biousse V, Vignal-Clermont C, Sergott RC, Sadun AA, Rebolleda Fernández G, Chwalisz BK, Banik R, Bazin F, Roux M, Cox ED, Taiel M, Sahel JA; LHON REFLECT Study Group
Brain 2023 Apr 19;146(4):1328-1341. doi: 10.1093/brain/awac421. PMID: 36350566Free PMC Article
Chen BS, Yu-Wai-Man P, Newman NJ
Curr Neurol Neurosci Rep 2022 Dec;22(12):881-892. Epub 2022 Nov 21 doi: 10.1007/s11910-022-01246-y. PMID: 36414808Free PMC Article
Davila-Siliezar P, Carter M, Milea D, Lee AG
Curr Opin Ophthalmol 2022 Nov 1;33(6):574-578. Epub 2022 Aug 24 doi: 10.1097/ICU.0000000000000891. PMID: 36066375

Prognosis

Shamsnajafabadi H, MacLaren RE, Cehajic-Kapetanovic J
Cells 2023 Aug 7;12(15) doi: 10.3390/cells12152013. PMID: 37566092Free PMC Article
Chow-Wing-Bom HT, Callaghan MF, Wang J, Wei S, Dick F, Yu-Wai-Man P, Dekker TM
Neuroimage Clin 2022;36:103240. Epub 2022 Oct 25 doi: 10.1016/j.nicl.2022.103240. PMID: 36510411Free PMC Article
Rigoli L, Caruso V, Salzano G, Lombardo F
Int J Environ Res Public Health 2022 Mar 9;19(6) doi: 10.3390/ijerph19063225. PMID: 35328914Free PMC Article
Iafusco D, Zanfardino A, Piscopo A, Curto S, Troncone A, Chianese A, Rollato AS, Testa V, Iafusco F, Maione G, Pennarella A, Boccabella L, Ozen G, Palma PL, Mazzaccara C, Tinto N, Miraglia Del Giudice E
Int J Environ Res Public Health 2022 Feb 27;19(5) doi: 10.3390/ijerph19052755. PMID: 35270448Free PMC Article
Lenaers G, Hamel C, Delettre C, Amati-Bonneau P, Procaccio V, Bonneau D, Reynier P, Milea D
Orphanet J Rare Dis 2012 Jul 9;7:46. doi: 10.1186/1750-1172-7-46. PMID: 22776096Free PMC Article

Clinical prediction guides

Yang YP, Foustine S, Hsiao YJ, Tsai ET, Tsai FT, Wang CL, Ko YL, Tai HY, Tsai YC, Yang CH, Fu YJ, Wang AG, Chien Y
J Chin Med Assoc 2023 Jun 1;86(6):539-541. Epub 2023 Apr 10 doi: 10.1097/JCMA.0000000000000927. PMID: 37027535
Newman NJ, Yu-Wai-Man P, Subramanian PS, Moster ML, Wang AG, Donahue SP, Leroy BP, Carelli V, Biousse V, Vignal-Clermont C, Sergott RC, Sadun AA, Rebolleda Fernández G, Chwalisz BK, Banik R, Bazin F, Roux M, Cox ED, Taiel M, Sahel JA; LHON REFLECT Study Group
Brain 2023 Apr 19;146(4):1328-1341. doi: 10.1093/brain/awac421. PMID: 36350566Free PMC Article
Gupta PR, Gospe SM , III
Ophthalmic Genet 2023 Oct;44(5):469-474. Epub 2022 Oct 19 doi: 10.1080/13816810.2022.2135112. PMID: 36262091
Delvecchio M, Iacoviello M, Pantaleo A, Resta N
Int J Environ Res Public Health 2021 Apr 30;18(9) doi: 10.3390/ijerph18094796. PMID: 33946243Free PMC Article
Newman NJ, Biousse V
Eye (Lond) 2004 Nov;18(11):1144-60. doi: 10.1038/sj.eye.6701591. PMID: 15534600

Recent systematic reviews

Finsterer J
J Clin Neuromuscul Dis 2023 Mar 1;24(3):140-146. doi: 10.1097/CND.0000000000000422. PMID: 36809201
Petzold A, Balcer LJ, Calabresi PA, Costello F, Frohman TC, Frohman EM, Martinez-Lapiscina EH, Green AJ, Kardon R, Outteryck O, Paul F, Schippling S, Vermersch P, Villoslada P, Balk LJ; ERN-EYE IMSVISUAL
Lancet Neurol 2017 Oct;16(10):797-812. Epub 2017 Sep 12 doi: 10.1016/S1474-4422(17)30278-8. PMID: 28920886
Law SK, Li T
Cochrane Database Syst Rev 2013 May 31;5(5):CD006030. doi: 10.1002/14651858.CD006030.pub3. PMID: 23728656Free PMC Article
Terelak-Borys B, Skonieczna K, Grabska-Liberek I
Med Sci Monit 2012 Aug;18(8):RA138-144. doi: 10.12659/msm.883260. PMID: 22847215Free PMC Article
Law SK, Li T
Cochrane Database Syst Rev 2007 Oct 17;(4):CD006030. doi: 10.1002/14651858.CD006030.pub2. PMID: 17943876Free PMC Article

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