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Optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome

MedGen UID:
1807322
•Concept ID:
C5681321
•
Disease or Syndrome
Synonyms: Optic atrophy, ataxia, peripheral neuropathy, global developmental delay syndrome; optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome
SNOMED CT: Optic atrophy, ataxia, peripheral neuropathy, global developmental delay syndrome (1222655009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Monarch Initiative: MONDO:0034092
Orphanet: ORPHA543470

Definition

A rare mitochondrial disease with characteristics of a variable clinical phenotype with the core features of optic atrophy, ataxia and hypotonia. Additional common manifestations include global developmental delay with or without regression, neuropathy, spasticity, and microcephaly, less frequently seizures, movement disorder, hearing loss and respiratory failure. Brain imaging may show abnormalities of the corpus callosum, basal ganglia and midbrain, cerebral or cerebellar atrophy, or white matter abnormalities. The condition is frequently fatal at an early age. [from SNOMEDCT_US]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • Optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome

Professional guidelines

PubMed

Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline.
Nordenström A, Ahmed SF, van den Akker E, Blair J, Bonomi M, Brachet C, Broersen LHA, Claahsen-van der Grinten HL, Dessens AB, Gawlik A, Gravholt CH, Juul A, Krausz C, Raivio T, Smyth A, Touraine P, Vitali D, Dekkers OM
Eur J Endocrinol 2022 Apr 21;186(6):G9-G49. doi: 10.1530/EJE-22-0073. PMID: 35353710Free PMC Article
Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism.
Stamou MI, Georgopoulos NA
Metabolism 2018 Sep;86:124-134. Epub 2017 Nov 3 doi: 10.1016/j.metabol.2017.10.012. PMID: 29108899Free PMC Article
Craniosynostosis - Recognition, clinical characteristics, and treatment.
Kajdic N, Spazzapan P, Velnar T
Bosn J Basic Med Sci 2018 May 20;18(2):110-116. doi: 10.17305/bjbms.2017.2083. PMID: 28623672Free PMC Article

Recent clinical studies

Etiology

Updates on Sturge-Weber Syndrome.
Yeom S, Comi AM
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Rhomboencephalosynapsis: Review of the Literature.
Fouda MA, Kim TY, Cohen AR
World Neurosurg 2022 Mar;159:48-53. Epub 2021 Dec 22 doi: 10.1016/j.wneu.2021.12.062. PMID: 34954057
Molecular findings among patients referred for clinical whole-exome sequencing.
Yang Y, Muzny DM, Xia F, Niu Z, Person R, Ding Y, Ward P, Braxton A, Wang M, Buhay C, Veeraraghavan N, Hawes A, Chiang T, Leduc M, Beuten J, Zhang J, He W, Scull J, Willis A, Landsverk M, Craigen WJ, Bekheirnia MR, Stray-Pedersen A, Liu P, Wen S, Alcaraz W, Cui H, Walkiewicz M, Reid J, Bainbridge M, Patel A, Boerwinkle E, Beaudet AL, Lupski JR, Plon SE, Gibbs RA, Eng CM
JAMA 2014 Nov 12;312(18):1870-9. doi: 10.1001/jama.2014.14601. PMID: 25326635Free PMC Article
Joubert syndrome and related disorders.
Valente EM, Dallapiccola B, Bertini E
Handb Clin Neurol 2013;113:1879-88. doi: 10.1016/B978-0-444-59565-2.00058-7. PMID: 23622411
Cerebro-oculo-facio-skeletal syndrome.
Suzumura H, Arisaka O
Adv Exp Med Biol 2010;685:210-4. doi: 10.1007/978-1-4419-6448-9_19. PMID: 20687508

Diagnosis

Updates on Sturge-Weber Syndrome.
Yeom S, Comi AM
Stroke 2022 Dec;53(12):3769-3779. Epub 2022 Oct 20 doi: 10.1161/STROKEAHA.122.038585. PMID: 36263782Free PMC Article
Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism.
Stamou MI, Georgopoulos NA
Metabolism 2018 Sep;86:124-134. Epub 2017 Nov 3 doi: 10.1016/j.metabol.2017.10.012. PMID: 29108899Free PMC Article
Craniosynostosis - Recognition, clinical characteristics, and treatment.
Kajdic N, Spazzapan P, Velnar T
Bosn J Basic Med Sci 2018 May 20;18(2):110-116. doi: 10.17305/bjbms.2017.2083. PMID: 28623672Free PMC Article
Molecular findings among patients referred for clinical whole-exome sequencing.
Yang Y, Muzny DM, Xia F, Niu Z, Person R, Ding Y, Ward P, Braxton A, Wang M, Buhay C, Veeraraghavan N, Hawes A, Chiang T, Leduc M, Beuten J, Zhang J, He W, Scull J, Willis A, Landsverk M, Craigen WJ, Bekheirnia MR, Stray-Pedersen A, Liu P, Wen S, Alcaraz W, Cui H, Walkiewicz M, Reid J, Bainbridge M, Patel A, Boerwinkle E, Beaudet AL, Lupski JR, Plon SE, Gibbs RA, Eng CM
JAMA 2014 Nov 12;312(18):1870-9. doi: 10.1001/jama.2014.14601. PMID: 25326635Free PMC Article
Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome).
McDonald-McGinn DM, Sullivan KE
Medicine (Baltimore) 2011 Jan;90(1):1-18. doi: 10.1097/MD.0b013e3182060469. PMID: 21200182

Therapy

Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline.
Nordenström A, Ahmed SF, van den Akker E, Blair J, Bonomi M, Brachet C, Broersen LHA, Claahsen-van der Grinten HL, Dessens AB, Gawlik A, Gravholt CH, Juul A, Krausz C, Raivio T, Smyth A, Touraine P, Vitali D, Dekkers OM
Eur J Endocrinol 2022 Apr 21;186(6):G9-G49. doi: 10.1530/EJE-22-0073. PMID: 35353710Free PMC Article
Ocular Features of Cerebro-Costo-Mandibular Syndrome.
Hameed Z, Taylor S, Lindfield D
J Glaucoma 2018 Jan;27(1):e21-e23. doi: 10.1097/IJG.0000000000000815. PMID: 29117007
Optic Pathway Gliomas: Clinical Manifestation, Treatment, and Follow-Up.
Ertiaei A, Hanaei S, Habibi Z, Moradi E, Nejat F
Pediatr Neurosurg 2016;51(5):223-8. Epub 2016 Apr 16 doi: 10.1159/000445064. PMID: 27082859
Sleep in children with autism spectrum disorder.
Kotagal S, Broomall E
Pediatr Neurol 2012 Oct;47(4):242-51. doi: 10.1016/j.pediatrneurol.2012.05.007. PMID: 22964437
The fetal trimethadione syndrome.
Zackai EH, Mellman WJ, Neiderer B, Hanson JW
J Pediatr 1975 Aug;87(2):280-4. doi: 10.1016/s0022-3476(75)80603-2. PMID: 50427

Prognosis

POU3F3-related disorder: Defining the phenotype and expanding the molecular spectrum.
Rossi A, Blok LS, Neuser S, Klöckner C, Platzer K, Faivre LO, Weigand H, Dentici ML, Tartaglia M, Niceta M, Alfieri P, Srivastava S, Coulter D, Smith L, Vinorum K, Cappuccio G, Brunetti-Pierri N, Torun D, Arslan M, Lauridsen MF, Murch O, Irving R, Lynch SA, Mehta SG, Carmichael J, Zonneveld-Huijssoon E, de Vries B, Kleefstra T, Johannesen KM, Westphall IT, Hughes SS, Smithson S, Evans J, Dudding-Byth T, Simon M, van Binsbergen E, Herkert JC, Beunders G, Oppermann H, Bakal M, Møller RS, Rubboli G, Bayat A
Clin Genet 2023 Aug;104(2):186-197. Epub 2023 May 10 doi: 10.1111/cge.14353. PMID: 37165752Free PMC Article
The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders.
Saffari A, Lau T, Tajsharghi H, Karimiani EG, Kariminejad A, Efthymiou S, Zifarelli G, Sultan T, Toosi MB, Sedighzadeh S, Siu VM, Ortigoza-Escobar JD, AlShamsi AM, Ibrahim S, Al-Sannaa NA, Al-Hertani W, Sandra W, Tarnopolsky M, Alavi S, Li C, Day-Salvatore DL, Martínez-González MJ, Levandoski KM, Bedoukian E, Madan-Khetarpal S, Idleburg MJ, Menezes MJ, Siddharth A, Platzer K, Oppermann H, Smitka M, Collins F, Lek M, Shahrooei M, Ghavideldarestani M, Herman I, Rendu J, Faure J, Baker J, Bhambhani V, Calderwood L, Akhondian J, Imannezhad S, Mirzadeh HS, Hashemi N, Doosti M, Safi M, Ahangari N, Torbati PN, Abedini S, Salpietro V, Gulec EY, Eshaghian S, Ghazavi M, Pascher MT, Vogel M, Abicht A, Moutton S, Bruel AL, Rieubland C, Gallati S, Strom TM, Lochmüller H, Mohammadi MH, Alvi JR, Zackai EH, Keena BA, Skraban CM, Berger SI, Andrew EH, Rahimian E, Morrow MM, Wentzensen IM, Millan F, Henderson LB, Dafsari HS, Jungbluth H, Gomez-Ospina N, McRae A, Peter M, Veltra D, Marinakis NM, Sofocleous C, Ashrafzadeh F, Pehlivan D, Lemke JR, Melki J, Benezit A, Bauer P, Weis D, Lupski JR, Senderek J, Christodoulou J, Chung WK, Goodchild R, Offiah AC, Moreno-De-Luca A, Suri M, Ebrahimi-Fakhari D, Houlden H, Maroofian R
Brain 2023 Aug 1;146(8):3273-3288. doi: 10.1093/brain/awad039. PMID: 36757831Free PMC Article
Rare EIF4A2 variants are associated with a neurodevelopmental disorder characterized by intellectual disability, hypotonia, and epilepsy.
Paul MS, Duncan AR, Genetti CA, Pan H, Jackson A, Grant PE, Shi J, Pinelli M, Brunetti-Pierri N, Garza-Flores A, Shahani D, Saneto RP, Zampino G, Leoni C, Agolini E, Novelli A, Blümlein U, Haack TB, Heinritz W, Matzker E, Alhaddad B, Abou Jamra R, Bartolomaeus T, AlHamdan S, Carapito R, Isidor B, Bahram S, Ritter A, Izumi K, Shakked BP, Barel O, Ben Zeev B, Begtrup A, Carere DA, Mullegama SV, Palculict TB, Calame DG, Schwan K, Aycinena ARP, Traberg R; Genomics England Research Consortium, Douzgou S, Pirt H, Ismayilova N, Banka S, Chao HT, Agrawal PB
Am J Hum Genet 2023 Jan 5;110(1):120-145. Epub 2022 Dec 16 doi: 10.1016/j.ajhg.2022.11.011. PMID: 36528028Free PMC Article
Walker-Warburg syndrome.
Vajsar J, Schachter H
Orphanet J Rare Dis 2006 Aug 3;1:29. doi: 10.1186/1750-1172-1-29. PMID: 16887026Free PMC Article
Encephalocraniocutaneous lipomatosis.
Gawel J, Schwartz RA, Józwiak S
J Cutan Med Surg 2003 Jan-Feb;7(1):61-5. Epub 2002 Oct 9 doi: 10.1007/s10227-002-1142-x. PMID: 12362260

Clinical prediction guides

POU3F3-related disorder: Defining the phenotype and expanding the molecular spectrum.
Rossi A, Blok LS, Neuser S, Klöckner C, Platzer K, Faivre LO, Weigand H, Dentici ML, Tartaglia M, Niceta M, Alfieri P, Srivastava S, Coulter D, Smith L, Vinorum K, Cappuccio G, Brunetti-Pierri N, Torun D, Arslan M, Lauridsen MF, Murch O, Irving R, Lynch SA, Mehta SG, Carmichael J, Zonneveld-Huijssoon E, de Vries B, Kleefstra T, Johannesen KM, Westphall IT, Hughes SS, Smithson S, Evans J, Dudding-Byth T, Simon M, van Binsbergen E, Herkert JC, Beunders G, Oppermann H, Bakal M, Møller RS, Rubboli G, Bayat A
Clin Genet 2023 Aug;104(2):186-197. Epub 2023 May 10 doi: 10.1111/cge.14353. PMID: 37165752Free PMC Article
The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders.
Saffari A, Lau T, Tajsharghi H, Karimiani EG, Kariminejad A, Efthymiou S, Zifarelli G, Sultan T, Toosi MB, Sedighzadeh S, Siu VM, Ortigoza-Escobar JD, AlShamsi AM, Ibrahim S, Al-Sannaa NA, Al-Hertani W, Sandra W, Tarnopolsky M, Alavi S, Li C, Day-Salvatore DL, Martínez-González MJ, Levandoski KM, Bedoukian E, Madan-Khetarpal S, Idleburg MJ, Menezes MJ, Siddharth A, Platzer K, Oppermann H, Smitka M, Collins F, Lek M, Shahrooei M, Ghavideldarestani M, Herman I, Rendu J, Faure J, Baker J, Bhambhani V, Calderwood L, Akhondian J, Imannezhad S, Mirzadeh HS, Hashemi N, Doosti M, Safi M, Ahangari N, Torbati PN, Abedini S, Salpietro V, Gulec EY, Eshaghian S, Ghazavi M, Pascher MT, Vogel M, Abicht A, Moutton S, Bruel AL, Rieubland C, Gallati S, Strom TM, Lochmüller H, Mohammadi MH, Alvi JR, Zackai EH, Keena BA, Skraban CM, Berger SI, Andrew EH, Rahimian E, Morrow MM, Wentzensen IM, Millan F, Henderson LB, Dafsari HS, Jungbluth H, Gomez-Ospina N, McRae A, Peter M, Veltra D, Marinakis NM, Sofocleous C, Ashrafzadeh F, Pehlivan D, Lemke JR, Melki J, Benezit A, Bauer P, Weis D, Lupski JR, Senderek J, Christodoulou J, Chung WK, Goodchild R, Offiah AC, Moreno-De-Luca A, Suri M, Ebrahimi-Fakhari D, Houlden H, Maroofian R
Brain 2023 Aug 1;146(8):3273-3288. doi: 10.1093/brain/awad039. PMID: 36757831Free PMC Article
Rare EIF4A2 variants are associated with a neurodevelopmental disorder characterized by intellectual disability, hypotonia, and epilepsy.
Paul MS, Duncan AR, Genetti CA, Pan H, Jackson A, Grant PE, Shi J, Pinelli M, Brunetti-Pierri N, Garza-Flores A, Shahani D, Saneto RP, Zampino G, Leoni C, Agolini E, Novelli A, Blümlein U, Haack TB, Heinritz W, Matzker E, Alhaddad B, Abou Jamra R, Bartolomaeus T, AlHamdan S, Carapito R, Isidor B, Bahram S, Ritter A, Izumi K, Shakked BP, Barel O, Ben Zeev B, Begtrup A, Carere DA, Mullegama SV, Palculict TB, Calame DG, Schwan K, Aycinena ARP, Traberg R; Genomics England Research Consortium, Douzgou S, Pirt H, Ismayilova N, Banka S, Chao HT, Agrawal PB
Am J Hum Genet 2023 Jan 5;110(1):120-145. Epub 2022 Dec 16 doi: 10.1016/j.ajhg.2022.11.011. PMID: 36528028Free PMC Article
De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith-Magenis syndrome.
Vetrini F, McKee S, Rosenfeld JA, Suri M, Lewis AM, Nugent KM, Roeder E, Littlejohn RO, Holder S, Zhu W, Alaimo JT, Graham B, Harris JM, Gibson JB, Pastore M, McBride KL, Komara M, Al-Gazali L, Al Shamsi A, Fanning EA, Wierenga KJ, Scott DA, Ben-Neriah Z, Meiner V, Cassuto H, Elpeleg O, Holder JL Jr, Burrage LC, Seaver LH, Van Maldergem L, Mahida S, Soul JS, Marlatt M, Matyakhina L, Vogt J, Gold JA, Park SM, Varghese V, Lampe AK, Kumar A, Lees M, Holder-Espinasse M, McConnell V, Bernhard B, Blair E, Harrison V; DDD study, Muzny DM, Gibbs RA, Elsea SH, Posey JE, Bi W, Lalani S, Xia F, Yang Y, Eng CM, Lupski JR, Liu P
Genome Med 2019 Feb 28;11(1):12. doi: 10.1186/s13073-019-0623-0. PMID: 30819258Free PMC Article
Molecular findings among patients referred for clinical whole-exome sequencing.
Yang Y, Muzny DM, Xia F, Niu Z, Person R, Ding Y, Ward P, Braxton A, Wang M, Buhay C, Veeraraghavan N, Hawes A, Chiang T, Leduc M, Beuten J, Zhang J, He W, Scull J, Willis A, Landsverk M, Craigen WJ, Bekheirnia MR, Stray-Pedersen A, Liu P, Wen S, Alcaraz W, Cui H, Walkiewicz M, Reid J, Bainbridge M, Patel A, Boerwinkle E, Beaudet AL, Lupski JR, Plon SE, Gibbs RA, Eng CM
JAMA 2014 Nov 12;312(18):1870-9. doi: 10.1001/jama.2014.14601. PMID: 25326635Free PMC Article

Recent systematic reviews

Clinical and Therapeutic Aspects of Sideroblastic Anaemia with B-Cell Immunodeficiency, Periodic Fever and Developmental Delay (SIFD) Syndrome: a Systematic Review.
Maccora I, Ramanan AV, Wiseman D, Marrani E, Mastrolia MV, Simonini G
J Clin Immunol 2023 Jan;43(1):1-30. Epub 2022 Aug 19 doi: 10.1007/s10875-022-01343-0. PMID: 35984545Free PMC Article
Correlation between Phenotype and Genotype in CTNNB1 Syndrome: A Systematic Review of the Literature.
Miroševič Š, Khandelwal S, Sušjan P, Žakelj N, Gosar D, Forstnerič V, Lainšček D, Jerala R, Osredkar D
Int J Mol Sci 2022 Oct 19;23(20) doi: 10.3390/ijms232012564. PMID: 36293418Free PMC Article
Ophthalmologic and facial abnormalities of Nicolaides-Baraitser syndrome.
Simmers R, Goodwin A, Al Saif H, Couser N
Ophthalmic Genet 2022 Oct;43(5):699-702. Epub 2022 Jun 27 doi: 10.1080/13816810.2022.2089358. PMID: 35762114
Eye and ocular adnexa manifestations of MED12-related disorders.
Shah A, Bapna M, Al-Saif H, Li R, Couser NL
Ophthalmic Genet 2022 Feb;43(1):126-129. Epub 2021 Oct 20 doi: 10.1080/13816810.2021.1989601. PMID: 34670449
Phenotypic spectrum of short-chain enoyl-Coa hydratase-1 (ECHS1) deficiency.
Masnada S, Parazzini C, Bini P, Barbarini M, Alberti L, Valente M, Chiapparini L, De Silvestri A, Doneda C, Iascone M, Saielli LA, Cereda C, Veggiotti P, Corbetta C, Tonduti D
Eur J Paediatr Neurol 2020 Sep;28:151-158. Epub 2020 Jul 29 doi: 10.1016/j.ejpn.2020.07.007. PMID: 32800686

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