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C11orf73-related autosomal recessive hypomyelinating leukodystrophy

MedGen UID:
1798879
•Concept ID:
C5567456
•
Disease or Syndrome
Synonyms: C11ORF73-related autosomal recessive hypomyelinating leukodystrophy; c11orf73-related autosomal recessive hypomyelinating leukodystrophy; C11ORF73-related autosomal recessive hypomyelinating leukoencephalopathy; Hypomyelinating leukodystrophy due to HIKESHI deficiency; Hypomyelinating leukodystrophy due to hikeshi deficiency; hypomyelinating leukodystrophy due to hikeshi deficiency
SNOMED CT: C11ORF73-related autosomal recessive hypomyelinating leukodystrophy (1172595004); C11ORF73-related autosomal recessive hypomyelinating leukoencephalopathy (1172595004); Hypomyelinating leukodystrophy due to HIKESHI deficiency (1172595004)
 
Monarch Initiative: MONDO:0044642
Orphanet: ORPHA495844

Definition

A rare leukodystrophy characterized by infantile onset of lower limb spasticity and severe developmental delay associated with delayed myelination and periventricular white matter abnormalities. Other reported signs and symptoms include microcephaly, optic atrophy, nystagmus, ataxia, or seizures. [from SNOMEDCT_US]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVC11orf73-related autosomal recessive hypomyelinating leukodystrophy

Professional guidelines

PubMed

Recessive Ataxia Differential Diagnosis Algorithm (RADIAL) Versus Specific Niemann-Pick Type C Suspicion Indices: A Retrospective Algorithm Comparison.
Anheim M, Torres Martin JV, Kolb SA
Cerebellum 2020 Apr;19(2):243-251. doi: 10.1007/s12311-020-01102-0. PMID: 31933160

Recent clinical studies

Etiology

A novel variant of the POLR3A gene in a patient with hypomyelinating POLR3-related leukodystrophy.
Yoon Han J, Gon Cho Y, Park J, Jang W
Clin Chim Acta 2022 Aug 1;533:15-21. Epub 2022 Jun 9 doi: 10.1016/j.cca.2022.06.007. PMID: 35691411
Hypomyelination and Congenital Cataract: Clinical, Imaging, and Genetic Findings in Three Tunisian Families and Literature Review.
Kraoua I, Bouyacoub Y, Drissi C, Chargui M, Rebai I, Chebil A, Klaa H, Benrhouma H, Hassen A, Gouider-Khouja N, Abdelhak S, Boespflug-Tanguy O, Youssef-Turki IB, Dorboz I
Neuropediatrics 2021 Aug;52(4):302-309. Epub 2021 Jun 30 doi: 10.1055/s-0041-1728654. PMID: 34192786
Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C.
Pelletier F, Perrier S, Cayami FK, Mirchi A, Saikali S, Tran LT, Ulrick N, Guerrero K, Rampakakis E, van Spaendonk RML, Naidu S, Pohl D, Gibson WT, Demos M, Goizet C, Tejera-Martin I, Potic A, Fogel BL, Brais B, Sylvain M, Sébire G, Lourenço CM, Bonkowsky JL, Catsman-Berrevoets C, Pinto PS, Tirupathi S, Strømme P, de Grauw T, Gieruszczak-Bialek D, Krägeloh-Mann I, Mierzewska H, Philippi H, Rankin J, Atik T, Banwell B, Benko WS, Blaschek A, Bley A, Boltshauser E, Bratkovic D, Brozova K, Cimas I, Clough C, Corenblum B, Dinopoulos A, Dolan G, Faletra F, Fernandez R, Fletcher J, Garcia Garcia ME, Gasparini P, Gburek-Augustat J, Gonzalez Moron D, Hamati A, Harting I, Hertzberg C, Hill A, Hobson GM, Innes AM, Kauffman M, Kirwin SM, Kluger G, Kolditz P, Kotzaeridou U, La Piana R, Liston E, McClintock W, McEntagart M, McKenzie F, Melançon S, Misbahuddin A, Suri M, Monton FI, Moutton S, Murphy RPJ, Nickel M, Onay H, Orcesi S, Özkınay F, Patzer S, Pedro H, Pekic S, Pineda Marfa M, Pizzino A, Plecko B, Poll-The BT, Popovic V, Rating D, Rioux MF, Rodriguez Espinosa N, Ronan A, Ostergaard JR, Rossignol E, Sanchez-Carpintero R, Schossig A, Senbil N, Sønderberg Roos LK, Stevens CA, Synofzik M, Sztriha L, Tibussek D, Timmann D, Tonduti D, van de Warrenburg BP, Vázquez-López M, Venkateswaran S, Wasling P, Wassmer E, Webster RI, Wiegand G, Yoon G, Rotteveel J, Schiffmann R, van der Knaap MS, Vanderver A, Martos-Moreno GÁ, Polychronakos C, Wolf NI, Bernard G
J Clin Endocrinol Metab 2021 Jan 23;106(2):e660-e674. doi: 10.1210/clinem/dgaa700. PMID: 33005949Free PMC Article
An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies.
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Genetic and phenotypic characterization of NKX6-2-related spastic ataxia and hypomyelination.
Chelban V, Alsagob M, Kloth K, Chirita-Emandi A, Vandrovcova J, Maroofian R, Davagnanam I, Bakhtiari S, AlSayed MD, Rahbeeni Z, AlZaidan H, Malintan NT, Johannsen J, Efthymiou S, Ghayoor Karimiani E, Mankad K, Al-Shahrani SA, Beiraghi Toosi M, AlShammari M, Groppa S, Haridy NA, AlQuait L, Qari A, Huma R, Salih MA, Almass R, Almutairi FB, Hamad MH, Alorainy IA, Ramzan K, Imtiaz F, Puiu M, Kruer MC, Bierhals T, Wood NW, Colak D, Houlden H, Kaya N
Eur J Neurol 2020 Feb;27(2):334-342. Epub 2019 Oct 17 doi: 10.1111/ene.14082. PMID: 31509304Free PMC Article

Diagnosis

Hypomyelination caused by a novel homozygous pathogenic variant in FOLR1: complete clinical and radiological recovery with oral folinic acid therapy and review of the literature.
Potic A, Perrier S, Radovic T, Gavrilovic S, Ostojic J, Tran LT, Thiffault I, Pastinen T, Schiffmann R, Bernard G
Orphanet J Rare Dis 2023 Jul 13;18(1):187. doi: 10.1186/s13023-023-02802-6. PMID: 37443037Free PMC Article
An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies.
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Genetic and phenotypic characterization of NKX6-2-related spastic ataxia and hypomyelination.
Chelban V, Alsagob M, Kloth K, Chirita-Emandi A, Vandrovcova J, Maroofian R, Davagnanam I, Bakhtiari S, AlSayed MD, Rahbeeni Z, AlZaidan H, Malintan NT, Johannsen J, Efthymiou S, Ghayoor Karimiani E, Mankad K, Al-Shahrani SA, Beiraghi Toosi M, AlShammari M, Groppa S, Haridy NA, AlQuait L, Qari A, Huma R, Salih MA, Almass R, Almutairi FB, Hamad MH, Alorainy IA, Ramzan K, Imtiaz F, Puiu M, Kruer MC, Bierhals T, Wood NW, Colak D, Houlden H, Kaya N
Eur J Neurol 2020 Feb;27(2):334-342. Epub 2019 Oct 17 doi: 10.1111/ene.14082. PMID: 31509304Free PMC Article
Expanding the clinical and genetic spectra of NKX6-2-related disorder.
Baldi C, Bertoli-Avella AM, Al-Sannaa N, Alfadhel M, Al-Thihli K, Alameer S, Elmonairy AA, Al Shamsi AM, Abdelrahman HA, Al-Gazali L, Shawli A, Al-Hakami F, Yavuz H, Kandaswamy KK, Rolfs A, Brandau O, Bauer P
Clin Genet 2018 May;93(5):1087-1092. doi: 10.1111/cge.13221. PMID: 29388673
Pelizaeus-Merzbacher disease, Pelizaeus-Merzbacher-like disease 1, and related hypomyelinating disorders.
Hobson GM, Garbern JY
Semin Neurol 2012 Feb;32(1):62-7. Epub 2012 Mar 15 doi: 10.1055/s-0032-1306388. PMID: 22422208

Therapy

Hypomyelination caused by a novel homozygous pathogenic variant in FOLR1: complete clinical and radiological recovery with oral folinic acid therapy and review of the literature.
Potic A, Perrier S, Radovic T, Gavrilovic S, Ostojic J, Tran LT, Thiffault I, Pastinen T, Schiffmann R, Bernard G
Orphanet J Rare Dis 2023 Jul 13;18(1):187. doi: 10.1186/s13023-023-02802-6. PMID: 37443037Free PMC Article

Prognosis

Hypomyelination caused by a novel homozygous pathogenic variant in FOLR1: complete clinical and radiological recovery with oral folinic acid therapy and review of the literature.
Potic A, Perrier S, Radovic T, Gavrilovic S, Ostojic J, Tran LT, Thiffault I, Pastinen T, Schiffmann R, Bernard G
Orphanet J Rare Dis 2023 Jul 13;18(1):187. doi: 10.1186/s13023-023-02802-6. PMID: 37443037Free PMC Article
Progress in elucidating pathophysiology of mucolipidosis IV.
Misko A, Wood L, Kiselyov K, Slaugenhaupt S, Grishchuk Y
Neurosci Lett 2021 Jun 11;755:135944. Epub 2021 May 11 doi: 10.1016/j.neulet.2021.135944. PMID: 33965501Free PMC Article
Genetic and phenotypic characterization of NKX6-2-related spastic ataxia and hypomyelination.
Chelban V, Alsagob M, Kloth K, Chirita-Emandi A, Vandrovcova J, Maroofian R, Davagnanam I, Bakhtiari S, AlSayed MD, Rahbeeni Z, AlZaidan H, Malintan NT, Johannsen J, Efthymiou S, Ghayoor Karimiani E, Mankad K, Al-Shahrani SA, Beiraghi Toosi M, AlShammari M, Groppa S, Haridy NA, AlQuait L, Qari A, Huma R, Salih MA, Almass R, Almutairi FB, Hamad MH, Alorainy IA, Ramzan K, Imtiaz F, Puiu M, Kruer MC, Bierhals T, Wood NW, Colak D, Houlden H, Kaya N
Eur J Neurol 2020 Feb;27(2):334-342. Epub 2019 Oct 17 doi: 10.1111/ene.14082. PMID: 31509304Free PMC Article
Novel POLR1C mutation in RNA polymerase III-related leukodystrophy with severe myoclonus and dystonia.
Kraoua I, Karkar A, Drissi C, Benrhouma H, Klaa H, Samaan S, Renaldo F, Elmaleh M, Ben Hamouda M, Abdelhak S, Boespflug-Tanguy O, Ben Youssef-Turki I, Dorboz I
Mol Genet Genomic Med 2019 Sep;7(9):e914. Epub 2019 Jul 31 doi: 10.1002/mgg3.914. PMID: 31368241Free PMC Article
4H Leukodystrophy: A Brain Magnetic Resonance Imaging Scoring System.
Vrij-van den Bos S, Hol JA, La Piana R, Harting I, Vanderver A, Barkhof F, Cayami F, van Wieringen WN, Pouwels PJW, van der Knaap MS, Bernard G, Wolf NI
Neuropediatrics 2017 Jun;48(3):152-160. Epub 2017 Mar 1 doi: 10.1055/s-0037-1599141. PMID: 28561206

Clinical prediction guides

Expanding the clinical and neuroimaging features of NKX6-2-related hereditary spastic ataxia type 8.
Hosseini Bereshneh A, Hosseipour S, Rasoulinezhad MS, Pak N, Garshasbi M, Tavasoli AR
Eur J Med Genet 2020 May;63(5):103868. Epub 2020 Jan 28 doi: 10.1016/j.ejmg.2020.103868. PMID: 32004679
Novel POLR1C mutation in RNA polymerase III-related leukodystrophy with severe myoclonus and dystonia.
Kraoua I, Karkar A, Drissi C, Benrhouma H, Klaa H, Samaan S, Renaldo F, Elmaleh M, Ben Hamouda M, Abdelhak S, Boespflug-Tanguy O, Ben Youssef-Turki I, Dorboz I
Mol Genet Genomic Med 2019 Sep;7(9):e914. Epub 2019 Jul 31 doi: 10.1002/mgg3.914. PMID: 31368241Free PMC Article
Expanding the clinical and genetic spectra of NKX6-2-related disorder.
Baldi C, Bertoli-Avella AM, Al-Sannaa N, Alfadhel M, Al-Thihli K, Alameer S, Elmonairy AA, Al Shamsi AM, Abdelrahman HA, Al-Gazali L, Shawli A, Al-Hakami F, Yavuz H, Kandaswamy KK, Rolfs A, Brandau O, Bauer P
Clin Genet 2018 May;93(5):1087-1092. doi: 10.1111/cge.13221. PMID: 29388673
Mutations in NKX6-2 Cause Progressive Spastic Ataxia and Hypomyelination.
Chelban V, Patel N, Vandrovcova J, Zanetti MN, Lynch DS, Ryten M, Botía JA, Bello O, Tribollet E, Efthymiou S, Davagnanam I; SYNAPSE Study Group, Bashiri FA, Wood NW, Rothman JE, Alkuraya FS, Houlden H
Am J Hum Genet 2017 Jun 1;100(6):969-977. doi: 10.1016/j.ajhg.2017.05.009. PMID: 28575651Free PMC Article
Inborn errors of brain myelin formation.
Boespflug-Tanguy O
Handb Clin Neurol 2013;113:1581-92. doi: 10.1016/B978-0-444-59565-2.00027-7. PMID: 23622380

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