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Semin Neurol 2021; 41(03): 303-308
DOI: 10.1055/s-0041-1725153
Review Article

Hereditary Myelopathies

Melissa A. Walker 
1   Division of Child Neurology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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Abstract

Hereditary myelopathies are an important and likely underappreciated component of neurogenetic disease. While previously distinctions have been made by age of onset, the growing power and availability of high-quality neuroimaging and next-generation sequencing are increasingly expanding classical phenotypes and diminishing the utility of age-based classifications. Increasingly, cases of “atypical” disease presentations are challenging past assumptions regarding the age of onset and survival in many disorders and identifying allelic syndromes in others. Despite this, there is poor awareness of the potential for spinal involvement in many diseases that typically affect the brain. Broadly speaking, congenital myelopathies can be neuroanatomically grouped into motor neuron, axonopathy, spinocerebellar, cerebroleukodystrophy, and pan-neuraxis (generally central nervous system predominant with associated axonopathy) disorders.

Here, we review hereditary causes of myelopathy, organized by neuroanatomy, and highlight atypical presentations. We discuss findings concerning an underlying genetic etiology for myelopathy, as well as practical, technical, and ethical considerations of diagnostic genetic testing.

Keywords

hereditary myelopathy - hereditary myelopathy - neurogenetic disease


Publication History

Article published online:
04 March 2021

© 2021. Thieme. All rights reserved.

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  • References

  • 1 Kolb SJ, Coffey CS, Yankey JW. et al; NeuroNEXT Clinical Trial Network on behalf of the NN101 SMA Biomarker Investigators. Natural history of infantile-onset spinal muscular atrophy. Ann Neurol 2017; 82 (06) 883-891
    CrossrefPubMedGoogle Scholar
  • 2 Chabanon A, Seferian AM, Daron A. et al; NatHis-SMA study group. Prospective and longitudinal natural history study of patients with Type 2 and 3 spinal muscular atrophy: baseline data NatHis-SMA study. PLoS One 2018; 13 (07) e0201004
    CrossrefPubMedGoogle Scholar
  • 3 Butchbach ME. Copy number variations in the survival motor neuron genes: implications for spinal muscular atrophy and other neurodegenerative diseases. Front Mol Biosci 2016; 3: 7
    CrossrefPubMedGoogle Scholar
  • 4 La Spada A. Spinal and bulbar muscular atrophy. In: Adam MP, Ardinger HH, Pagon RA. et al., eds. GeneReviews [Internet]. Seattle, WA:: University of Washington; 1999
    Google Scholar
  • 5 Kinsley L, Siddique T. Amyotrophic lateral sclerosis overview. In: Adam MP, Ardinger HH, Pagon RA. et al., eds. GeneReviews [Internet]. Seattle, WA:: University of Washington; 1993
    Google Scholar
  • 6 Drory VE, Birnbaum M, Peleg L, Goldman B, Korczyn AD. Hexosaminidase A deficiency is an uncommon cause of a syndrome mimicking amyotrophic lateral sclerosis. Muscle Nerve 2003; 28 (01) 109-112
    CrossrefPubMedGoogle Scholar
  • 7 Fink JK. Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms. Acta Neuropathol 2013; 126 (03) 307-328
    CrossrefPubMedGoogle Scholar
  • 8 Zhao X, Alvarado D, Rainier S. et al. Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia. Nat Genet 2001; 29 (03) 326-331
    CrossrefPubMedGoogle Scholar
  • 9 França Jr MC, Yasuda CL, Pereira FR. et al. White and grey matter abnormalities in patients with SPG11 mutations. J Neurol Neurosurg Psychiatry 2012; 83 (08) 828-833
    CrossrefPubMedGoogle Scholar
  • 10 Beaudin M, Klein CJ, Rouleau GA, Dupré N. Systematic review of autosomal recessive ataxias and proposal for a classification. Cerebellum Ataxias 2017; 4: 3
    CrossrefPubMedGoogle Scholar
  • 11 Sun YM, Lu C, Wu ZY. Spinocerebellar ataxia: relationship between phenotype and genotype - a review. Clin Genet 2016; 90 (04) 305-314
    CrossrefPubMedGoogle Scholar
  • 12 Lukas C, Hahn HK, Bellenberg B. et al. Spinal cord atrophy in spinocerebellar ataxia type 3 and 6: impact on clinical disability. J Neurol 2008; 255 (08) 1244-1249
    CrossrefPubMedGoogle Scholar
  • 13 Manto MU. The wide spectrum of spinocerebellar ataxias (SCAs). Cerebellum 2005; 4 (01) 2-6
    CrossrefPubMedGoogle Scholar
  • 14 Abe R, Sekijima Y, Kinoshita T. et al. Spinal form cerebrotendinous xanthomatosis patient with long spinal cord lesion. J Spinal Cord Med 2016; 39 (06) 726-729
    CrossrefPubMedGoogle Scholar
  • 15 Vanderver A, Tonduti D, Schiffmann R, Schmidt J, van der Knaap MS. Leukodystrophy overview. In: Adam MP, Ardinger HH, Pagon RA. et al., eds. GeneReviews [Internet]. Seattle, WA:: University of Washington; 1993
    Google Scholar
  • 16 Moser AB, Kreiter N, Bezman L. et al. Plasma very long chain fatty acids in 3,000 peroxisome disease patients and 29,000 controls. Ann Neurol 1999; 45 (01) 100-110
    CrossrefPubMedGoogle Scholar
  • 17 Kohlschütter A, Eichler F. Childhood leukodystrophies: a clinical perspective. Expert Rev Neurother 2011; 11 (10) 1485-1496
    CrossrefPubMedGoogle Scholar
  • 18 Arii J, Tanabe Y. Leigh syndrome: serial MR imaging and clinical follow-up. AJNR Am J Neuroradiol 2000; 21 (08) 1502-1509
    PubMedGoogle Scholar
  • 19 Leigh D. Subacute necrotizing encephalomyelopathy in an infant. J Neurol Neurosurg Psychiatry 1951; 14 (03) 216-221
    CrossrefPubMedGoogle Scholar
  • 20 Oldfors A, Holme E, Tulinius M, Larsson NG. Tissue distribution and disease manifestations of the tRNA(Lys) A-->G(8344) mitochondrial DNA mutation in a case of myoclonus epilepsy and ragged red fibres. Acta Neuropathol 1995; 90 (03) 328-333
    CrossrefPubMedGoogle Scholar
  • 21 Shen C, Xian W, Zhou H, Li X, Liang X, Chen L. Overlapping Leigh syndrome/myoclonic epilepsy with ragged red fibres in an adolescent patient with a mitochondrial DNA A8344G mutation. Front Neurol 2018; 9: 724
    CrossrefPubMedGoogle Scholar
  • 22 Hirano M, Ricci E, Koenigsberger MR. et al. MELAS: an original case and clinical criteria for diagnosis. Neuromuscul Disord 1992; 2 (02) 125-135
    CrossrefPubMedGoogle Scholar
  • 23 Holmøy T, Beiske AG, Zarnovicky S, Myro AZ, Røsjø E, Kerty E. Severe inflammatory disease activity 14 months after cessation of Natalizumab in a patient with Leber's optic neuropathy and multiple sclerosis - a case report. BMC Neurol 2016; 16 (01) 197
    CrossrefPubMedGoogle Scholar
  • 24 Palace J. Multiple sclerosis associated with Leber's hereditary optic neuropathy. J Neurol Sci 2009; 286 (1-2): 24-27
    CrossrefPubMedGoogle Scholar
  • 25 Galassi G, Maggi L, Lamantea E, Ariatti A, Malagoli M. C10ORF2 mutation associated with progressive external ophthalmoplegia and clinically isolated syndrome. Acta Neurol Belg 2017; 117 (04) 947-949
    CrossrefPubMedGoogle Scholar
  • 26 Brockington M, Alsanjari N, Sweeney MG, Morgan-Hughes JA, Scaravilli F, Harding AE. Kearns-Sayre syndrome associated with mitochondrial DNA deletion or duplication: a molecular genetic and pathological study. J Neurol Sci 1995; 131 (01) 78-87
    CrossrefPubMedGoogle Scholar
  • 27 Namavar Y, Barth PG, Poll-The BT, Baas F. Classification, diagnosis and potential mechanisms in pontocerebellar hypoplasia. Orphanet J Rare Dis 2011; 6: 50
    CrossrefPubMedGoogle Scholar
  • 28 Schlotawa L. et al. Multiple sulfatase deficiency. In: Adam MP, Ardinger HH, Pagon RA. et al., eds. GeneReviews [Internet]. Seattle, WA:: University of Washington; 1993
    Google Scholar
  • 29 Pueschel SM. Atlantoaxial instability and Down syndrome. Pediatrics 1988; 81 (06) 879-880
    PubMedGoogle Scholar
  • 30 Reichert R, Campos LG, Vairo F. et al. Neuroimaging findings in patients with mucopolysaccharidosis: what you really need to know. Radiographics 2016; 36 (05) 1448-1462
    CrossrefPubMedGoogle Scholar
  • 31 Illsinger S, Lücke T, Hartmann H. et al. Scheie syndrome: enzyme replacement therapy does not prevent progression of cervical myelopathy due to spinal cord compression. J Inherit Metab Dis 2009; 32 (Suppl. 01) S321-S325
    CrossrefPubMedGoogle Scholar