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Autosomal recessive axonal hereditary motor and sensory neuropathy

MedGen UID:
1842973
•Concept ID:
C5680194
•
Disease or Syndrome
Synonyms: AR-CMT2; Autosomal recessive axonal Charcot-Marie-Tooth disease type 2
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)
 
Orphanet: ORPHA91024

Professional guidelines

PubMed

HINT1 neuropathy: Expanding the genotype and phenotype spectrum.
Morel V, Campana-Salort E, Boyer A, Esselin F, Walther-Louvier U, Querin G, Latour P, Lia AS, Magdelaine C, Beze-Beyrie P, Behin A, Delague V, Levy N, Stojkovic T, Attarian S, Bonello-Palot N
Clin Genet 2022 Nov;102(5):379-390. Epub 2022 Aug 16 doi: 10.1111/cge.14198. PMID: 35882622Free PMC Article
Clinical features and management of hereditary spastic paraplegia.
Faber I, Servelhere KR, Martinez AR, D'Abreu A, Lopes-Cendes I, França MC Jr
Arq Neuropsiquiatr 2014 Mar;72(3):219-26. doi: 10.1590/0004-282x20130248. PMID: 24676440
Hereditary spastic paraplegia: genetic heterogeneity and genotype-phenotype correlation.
Fink JK, Hedera P
Semin Neurol 1999;19(3):301-9. doi: 10.1055/s-2008-1040846. PMID: 12194386

Recent clinical studies

Etiology

The hereditary spastic paraplegias.
Fink JK
Handb Clin Neurol 2023;196:59-88. doi: 10.1016/B978-0-323-98817-9.00022-3. PMID: 37620092
Early onset hereditary neuronopathies: an update on non-5q motor neuron diseases.
Zambon AA, Pini V, Bosco L, Falzone YM, Munot P, Muntoni F, Previtali SC
Brain 2023 Mar 1;146(3):806-822. doi: 10.1093/brain/awac452. PMID: 36445400Free PMC Article
Hereditary motor neuropathies.
Frasquet M, Sevilla T
Curr Opin Neurol 2022 Oct 1;35(5):562-570. Epub 2022 Aug 8 doi: 10.1097/WCO.0000000000001087. PMID: 35942667
Hereditary spastic paraplegia.
Murala S, Nagarajan E, Bollu PC
Neurol Sci 2021 Mar;42(3):883-894. Epub 2021 Jan 13 doi: 10.1007/s10072-020-04981-7. PMID: 33439395
The distal hereditary motor neuropathies.
Rossor AM, Kalmar B, Greensmith L, Reilly MM
J Neurol Neurosurg Psychiatry 2012 Jan;83(1):6-14. Epub 2011 Oct 25 doi: 10.1136/jnnp-2011-300952. PMID: 22028385

Diagnosis

The hereditary spastic paraplegias.
Fink JK
Handb Clin Neurol 2023;196:59-88. doi: 10.1016/B978-0-323-98817-9.00022-3. PMID: 37620092
Early onset hereditary neuronopathies: an update on non-5q motor neuron diseases.
Zambon AA, Pini V, Bosco L, Falzone YM, Munot P, Muntoni F, Previtali SC
Brain 2023 Mar 1;146(3):806-822. doi: 10.1093/brain/awac452. PMID: 36445400Free PMC Article
Hereditary motor neuropathies.
Frasquet M, Sevilla T
Curr Opin Neurol 2022 Oct 1;35(5):562-570. Epub 2022 Aug 8 doi: 10.1097/WCO.0000000000001087. PMID: 35942667
Hereditary spastic paraplegia.
Murala S, Nagarajan E, Bollu PC
Neurol Sci 2021 Mar;42(3):883-894. Epub 2021 Jan 13 doi: 10.1007/s10072-020-04981-7. PMID: 33439395
The distal hereditary motor neuropathies.
Rossor AM, Kalmar B, Greensmith L, Reilly MM
J Neurol Neurosurg Psychiatry 2012 Jan;83(1):6-14. Epub 2011 Oct 25 doi: 10.1136/jnnp-2011-300952. PMID: 22028385

Therapy

Intrathecal Gene Therapy for Giant Axonal Neuropathy.
Bharucha-Goebel DX, Todd JJ, Saade D, Norato G, Jain M, Lehky T, Bailey RM, Chichester JA, Calcedo R, Armao D, Foley AR, Mohassel P, Tesfaye E, Carlin BP, Seremula B, Waite M, Zein WM, Huryn LA, Crawford TO, Sumner CJ, Hoke A, Heiss JD, Charnas L, Hooper JE, Bouldin TW, Kang EM, Rybin D, Gray SJ, Bönnemann CG; GAN Trial Team
N Engl J Med 2024 Mar 21;390(12):1092-1104. doi: 10.1056/NEJMoa2307952. PMID: 38507752
A novel mutation in HINT1 gene causes autosomal recessive axonal neuropathy with neuromyotonia, effective treatment with carbamazepine and review of the literature.
Xu L, Wang G, Lv X, Zhang D, Yan C, Lin P
Acta Neurol Belg 2022 Oct;122(5):1305-1312. Epub 2022 Jun 29 doi: 10.1007/s13760-022-02006-y. PMID: 35767146
Giant axonal neuropathy: cross-sectional analysis of a large natural history cohort.
Bharucha-Goebel DX, Norato G, Saade D, Paredes E, Biancavilla V, Donkervoort S, Kaur R, Lehky T, Fink M, Armao D, Gray SJ, Waite M, Debs S, Averion G, Hu Y, Zein WM, Foley AR, Jain M, Bönnemann CG
Brain 2021 Nov 29;144(10):3239-3250. doi: 10.1093/brain/awab179. PMID: 34114613Free PMC Article
Natural history of Charcot-Marie-Tooth disease type 2A: a large international multicentre study.
Pipis M, Feely SME, Polke JM, Skorupinska M, Perez L, Shy RR, Laura M, Morrow JM, Moroni I, Pisciotta C, Taroni F, Vujovic D, Lloyd TE, Acsadi G, Yum SW, Lewis RA, Finkel RS, Herrmann DN, Day JW, Li J, Saporta M, Sadjadi R, Walk D, Burns J, Muntoni F, Ramchandren S, Horvath R, Johnson NE, Züchner S, Pareyson D, Scherer SS, Rossor AM, Shy ME, Reilly MM; Inherited Neuropathies Consortium - Rare Disease Clinical Research Network (INC-RDCRN)
Brain 2020 Dec 1;143(12):3589-3602. doi: 10.1093/brain/awaa323. PMID: 33415332Free PMC Article
Hereditary motor and sensory neuropathies or Charcot-Marie-Tooth diseases: an update.
Tazir M, Hamadouche T, Nouioua S, Mathis S, Vallat JM
J Neurol Sci 2014 Dec 15;347(1-2):14-22. Epub 2014 Oct 16 doi: 10.1016/j.jns.2014.10.013. PMID: 25454638

Prognosis

RTN2 deficiency results in an autosomal recessive distal motor neuropathy with lower limb spasticity.
Maroofian R, Sarraf P, O'Brien TJ, Kamel M, Cakar A, Elkhateeb N, Lau T, Patil SJ, Record CJ, Horga A, Essid M, Selim L, Benrhouma H, Ben Younes T, Zifarelli G, Pagnamenta AT, Bauer P, Khundadze M, Mirecki A, Kamel SM, Elmonem MA, Ghayoor Karimiani E, Jamshidi Y, Offiah AC, Rossor AM, Youssef-Turki IB, Hübner CA, Munot P, Reilly MM, Brown AEX, Nagy S, Houlden H
Brain 2024 Jul 5;147(7):2334-2343. doi: 10.1093/brain/awae091. PMID: 38527963Free PMC Article
SPTAN1 variants likely cause autosomal recessive complicated hereditary spastic paraplegia.
Xie F, Chen S, Liu P, Chen X, Luo W
J Hum Genet 2022 Mar;67(3):165-168. Epub 2021 Sep 16 doi: 10.1038/s10038-021-00975-1. PMID: 34526651
Natural history of Charcot-Marie-Tooth disease type 2A: a large international multicentre study.
Pipis M, Feely SME, Polke JM, Skorupinska M, Perez L, Shy RR, Laura M, Morrow JM, Moroni I, Pisciotta C, Taroni F, Vujovic D, Lloyd TE, Acsadi G, Yum SW, Lewis RA, Finkel RS, Herrmann DN, Day JW, Li J, Saporta M, Sadjadi R, Walk D, Burns J, Muntoni F, Ramchandren S, Horvath R, Johnson NE, Züchner S, Pareyson D, Scherer SS, Rossor AM, Shy ME, Reilly MM; Inherited Neuropathies Consortium - Rare Disease Clinical Research Network (INC-RDCRN)
Brain 2020 Dec 1;143(12):3589-3602. doi: 10.1093/brain/awaa323. PMID: 33415332Free PMC Article
Giant axonal neuropathy.
Hentati F, Hentati E, Amouri R
Handb Clin Neurol 2013;115:933-8. doi: 10.1016/B978-0-444-52902-2.00052-7. PMID: 23931822
Charcot-Marie-tooth disease.
Casasnovas C, Cano LM, Albertí A, Céspedes M, Rigo G
Foot Ankle Spec 2008 Dec;1(6):350-4. Epub 2008 Oct 22 doi: 10.1177/1938640008326247. PMID: 19825739

Clinical prediction guides

Decreasing ganglioside synthesis delays motor and cognitive symptom onset in Spg11 knockout mice.
Fortier M, Cauhapé M, Buono S, Becker J, Menuet A, Branchu J, Ricca I, Mero S, Dorgham K, El Hachimi KH, Dobrenis K, Colsch B, Samaroo D, Devaux M, Durr A, Stevanin G, Santorelli FM, Colombo S, Cowling B, Darios F
Neurobiol Dis 2024 Sep;199:106564. Epub 2024 Jun 12 doi: 10.1016/j.nbd.2024.106564. PMID: 38876323
Intrathecal Gene Therapy for Giant Axonal Neuropathy.
Bharucha-Goebel DX, Todd JJ, Saade D, Norato G, Jain M, Lehky T, Bailey RM, Chichester JA, Calcedo R, Armao D, Foley AR, Mohassel P, Tesfaye E, Carlin BP, Seremula B, Waite M, Zein WM, Huryn LA, Crawford TO, Sumner CJ, Hoke A, Heiss JD, Charnas L, Hooper JE, Bouldin TW, Kang EM, Rybin D, Gray SJ, Bönnemann CG; GAN Trial Team
N Engl J Med 2024 Mar 21;390(12):1092-1104. doi: 10.1056/NEJMoa2307952. PMID: 38507752
Pathogenic PSAT1 Variants and Autosomal Recessive Axonal Charcot-Marie-Tooth Disease With Ichthyosis.
Lu Y, Xing H, Liu C, Huang D, Sun C, Yu M, Meng L, Lv H, Zhang W, Wang Z, Yuan Y, Xie Z
Pediatr Neurol 2023 Mar;140:25-34. Epub 2022 Nov 24 doi: 10.1016/j.pediatrneurol.2022.11.013. PMID: 36599231
SPTAN1 variants likely cause autosomal recessive complicated hereditary spastic paraplegia.
Xie F, Chen S, Liu P, Chen X, Luo W
J Hum Genet 2022 Mar;67(3):165-168. Epub 2021 Sep 16 doi: 10.1038/s10038-021-00975-1. PMID: 34526651
Natural history of Charcot-Marie-Tooth disease type 2A: a large international multicentre study.
Pipis M, Feely SME, Polke JM, Skorupinska M, Perez L, Shy RR, Laura M, Morrow JM, Moroni I, Pisciotta C, Taroni F, Vujovic D, Lloyd TE, Acsadi G, Yum SW, Lewis RA, Finkel RS, Herrmann DN, Day JW, Li J, Saporta M, Sadjadi R, Walk D, Burns J, Muntoni F, Ramchandren S, Horvath R, Johnson NE, Züchner S, Pareyson D, Scherer SS, Rossor AM, Shy ME, Reilly MM; Inherited Neuropathies Consortium - Rare Disease Clinical Research Network (INC-RDCRN)
Brain 2020 Dec 1;143(12):3589-3602. doi: 10.1093/brain/awaa323. PMID: 33415332Free PMC Article

Recent systematic reviews

A Novel Mutation of the Membrane Metallo-Endopeptidase Gene Related to Late-Onset Hereditary Polyneuropathy: Case Report and Review of the Literature.
Tsamis KI, Xiromerisiou G, Nikas IP, Giannakis A, Konitsiotis S, Sarmas I
Lab Med 2022 Mar 7;53(2):210-214. doi: 10.1093/labmed/lmab060. PMID: 34480178
Intermediate Charcot-Marie-Tooth disease: an electrophysiological reappraisal and systematic review.
Berciano J, García A, Gallardo E, Peeters K, Pelayo-Negro AL, Álvarez-Paradelo S, Gazulla J, Martínez-Tames M, Infante J, Jordanova A
J Neurol 2017 Aug;264(8):1655-1677. Epub 2017 Mar 31 doi: 10.1007/s00415-017-8474-3. PMID: 28364294

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