Adult-onset autosomal dominant leukodystrophy and neuronal intranuclear inclusion disease: lessons from two new Chinese families.
Adult-onset autosomal dominant leukodystrophy (ADLD)
Gene
MRI
Neuronal intranuclear inclusion disease (NIID)
Journal
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
ISSN: 1590-3478
Titre abrégé: Neurol Sci
Pays: Italy
ID NLM: 100959175
Informations de publication
Date de publication:
Aug 2022
Aug 2022
Historique:
received:
17
02
2022
accepted:
02
04
2022
pubmed:
15
4
2022
medline:
6
8
2022
entrez:
14
4
2022
Statut:
ppublish
Résumé
Adult-onset autosomal dominant leukodystrophy (ADLD) is a rare genetic leukoencephalopathy caused by duplication of the lamin B1 gene (LMNB1) or LMNB1 upstream deletions. Neuronal intranuclear inclusion disease (NIID) is another leukoencephalopathy due to GGC repeat expansion in the 5'-untranslated region of the NOTCH2NLC gene. Here, we report two Chinese ADLD families with neuroimaging and clinical features mimicking NIID. We conducted detailed medical history inquiry, neurological examinations, and magnetic resonance imaging in the two families. Candidate gene sequencing and whole exome sequencing (WES) with copy number variation analysis were used to screen the genetic variations. The special points on the clinical and neuroimaging findings in the current families and differential diagnosis of ADLD with NIID are discussed. The two families presented with slowly progressive, multiple central nervous system symptoms, including spastic paraplegia, autonomic dysfunction, ataxia, deep sensory loss, and tremor. Clinical phenotypes were consistent within the family. Transient hypoglycemia and transient dilated pupils indicating autonomic dysfunctions were recorded for the first time in ADLD. Brain MRI showed band-like hyperintensities at the cortico-medullary junction on DWI, typical for NIID. Skin biopsy and genetic sequencing of the NOTCH2NCL gene did not support the diagnosis of NIID. Further whole exome sequencing (WES) identified the duplication mutation spanning the entire LMNB1 gene. The novel feature of transient hypoglycemia and dilated pupils broadens the spectrum of autonomic dysfunction in ADLD. Clinical manifestations and neuroimaging of ADLD can mimic NIID. Although ADLD is even rarer than NIID, the differential diagnosis of these two diseases should not be confused.
Identifiants
pubmed: 35419641
doi: 10.1007/s10072-022-06057-0
pii: 10.1007/s10072-022-06057-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-9Subventions
Organisme : Natural Science Foundation of Henan Province
ID : 212300410241
Informations de copyright
© 2022. Fondazione Società Italiana di Neurologia.
Références
Eldridge R, Anayiotos CP, Schlesinger S, Cowen D, Bever C, Patronas N et al (1984) Hereditary adult-onset leukodystrophy simulating chronic progressive multiple sclerosis. N Engl J Med 311(15):948–53. https://doi.org/10.1056/NEJM198410113111504
doi: 10.1056/NEJM198410113111504
pubmed: 6472420
Coffeen CM, McKenna CE, Koeppen AH, Plaster NM, Maragakis N, Mihalopoulos J et al (2000) Genetic localization of an autosomal dominant leukodystrophy mimicking chronic progressive multiple sclerosis to chromosome 5q31. Hum Mol Genet 9(5):787–93. https://doi.org/10.1093/hmg/9.5.787
doi: 10.1093/hmg/9.5.787
pubmed: 10749986
Padiath QS, Saigoh K, Schiffmann R, Asahara H, Yamada T, Koeppen A et al (2006) Lamin B1 duplications cause autosomal dominant leukodystrophy. Nat Genet 38(10):1114–23. https://doi.org/10.1038/ng1872
doi: 10.1038/ng1872
pubmed: 16951681
Marklund L, Melin M, Melberg A, Giedraitis V, Dahl N (2006) Adult-onset autosomal dominant leukodystrophy with autonomic symptoms restricted to 1.5 Mbp on chromosome 5q23. Am J Med Genet B Neuropsychiatr Genet 141B(6):608–14. https://doi.org/10.1002/ajmg.b.30342
doi: 10.1002/ajmg.b.30342
pubmed: 16823806
Giorgio E, Robyr D, Spielmann M, Ferrero E, Di Gregorio E, Imperiale D et al (2015) A large genomic deletion leads to enhancer adoption by the lamin B1 gene: a second path to autosomal dominant adult-onset demyelinating leukodystrophy (ADLD). Hum Mol Genet 24(11):3143–54. https://doi.org/10.1093/hmg/ddv065
doi: 10.1093/hmg/ddv065
pubmed: 25701871
pmcid: 4424952
Mezaki N, Miura T, Ogaki K, Eriguchi M, Mizuno Y, Komatsu K et al (2018) Duplication and deletion upstream of LMNB1 in autosomal dominant adult-onset leukodystrophy. Neurol Genet 4(6):e292. https://doi.org/10.1212/NXG.0000000000000292
doi: 10.1212/NXG.0000000000000292
pubmed: 30697589
pmcid: 6340331
Deng J, Gu M, Miao Y, Yao S, Zhu M, Fang P et al (2019) Long-read sequencing identified repeat expansions in the 5’UTR of the NOTCH2NLC gene from Chinese patients with neuronal intranuclear inclusion disease. J Med Genet 56(11):758–64. https://doi.org/10.1136/jmedgenet-2019-106268
doi: 10.1136/jmedgenet-2019-106268
pubmed: 31413119
Finnsson J, Sundblom J, Dahl N, Melberg A, Raininko R (2015) LMNB1-related autosomal-dominant leukodystrophy: clinical and radiological course. Ann Neurol 78(3):412–25. https://doi.org/10.1002/ana.24452
doi: 10.1002/ana.24452
pubmed: 26053668
pmcid: 5054845
Padiath QS (2019) Autosomal dominant leukodystrophy: a disease of the nuclear lamina. Front Cell Dev Biol 7:41. https://doi.org/10.3389/fcell.2019.00041
doi: 10.3389/fcell.2019.00041
pubmed: 30949481
pmcid: 6435485
Sundblom J, Melberg A, Kalimo H, Smits A, Raininko R (2009) MR imaging characteristics and neuropathology of the spinal cord in adult-onset autosomal dominant leukodystrophy with autonomic symptoms. AJNR Am J Neuroradiol 30(2):328–35. https://doi.org/10.3174/ajnr.A1354
doi: 10.3174/ajnr.A1354
pubmed: 18945794
pmcid: 7051393
Dai Y, Ma Y, Li S, Banerjee S, Liang S, Liu Q et al (2017) An LMNB1 duplication caused adult-onset autosomal dominant leukodystrophy in Chinese family: clinical manifestations, neuroradiology and genetic diagnosis. Front Mol Neurosci 10:215. https://doi.org/10.3389/fnmol.2017.00215
doi: 10.3389/fnmol.2017.00215
pubmed: 28769756
pmcid: 5513940
Zhang Y, Li J, Bai R, Wang J, Peng T, Chen L et al (2019) LMNB1-related adult-onset autosomal dominant leukodystrophy presenting as movement disorder: a case report and review of the literature. Front Neurosci. 13:1030. https://doi.org/10.3389/fnins.2019.01030
doi: 10.3389/fnins.2019.01030
pubmed: 31695592
pmcid: 6816284
Brown RT, Polinsky RJ, Schwankhaus J, Eldridge R, McFarland H, Schlesinger S et al (1987) Adrenergic dysfunction in hereditary adult-onset leukodystrophy. Neurology 37(8):1421–4. https://doi.org/10.1212/wnl.37.8.1421
doi: 10.1212/wnl.37.8.1421
pubmed: 3302762
Terlizzi R, Calandra-Buonaura G, Zanigni S, Barletta G, Capellari S, Guaraldi P et al (2016) A longitudinal study of a family with adult-onset autosomal dominant leukodystrophy: clinical, autonomic and neuropsychological findings. Auton Neurosci. 195:20–6. https://doi.org/10.1016/j.autneu.2016.02.005
doi: 10.1016/j.autneu.2016.02.005
pubmed: 26896090
Raza HK, Singh S, Rai P, Chansysouphanthong T, Amir A, Cui G et al (2020) Recent progress in neuronal intranuclear inclusion disease: a review of the literature. Neurol Sci 41(5):1019–25. https://doi.org/10.1007/s10072-019-04195-6
doi: 10.1007/s10072-019-04195-6
pubmed: 31897935
Lu X, Hong D (2021) Neuronal intranuclear inclusion disease: recognition and update. J Neural Transm (Vienna) 128(3):295–303. https://doi.org/10.1007/s00702-021-02313-3
doi: 10.1007/s00702-021-02313-3
Raininko R, Gosky M, Padiath QS (1993) LMNB1-related autosomal dominant leukodystrophy [updated 2021 Jul 15]. In: Adam MP, Ardinger HH, Pagon RA et al (eds.) GeneReviews®. University of Washington, Seattle
Tian Y, Wang JL, Huang W, Zeng S, Jiao B, Liu Z et al (2019) Expansion of human-specific GGC repeat in neuronal intranuclear inclusion disease-related disorders. Am J Hum Genet 105(1):166–76. https://doi.org/10.1016/j.ajhg.2019.05.013
doi: 10.1016/j.ajhg.2019.05.013
pubmed: 31178126
pmcid: 6612530
Ishihara T, Okamoto T, Saida K, Saitoh Y, Oda S, Sano T et al (2020) Neuronal intranuclear inclusion disease presenting with an MELAS-like episode in chronic polyneuropathy. Neurol Genet. 6(6):e531. https://doi.org/10.1212/NXG.0000000000000531
doi: 10.1212/NXG.0000000000000531
pubmed: 33324757
pmcid: 7713717
Chen H, Lu L, Wang B, Cui G, Wang X, Wang Y et al (2020) Re-defining the clinicopathological spectrum of neuronal intranuclear inclusion disease. Ann Clin Transl Neurol. 7(10):1930–41. https://doi.org/10.1002/acn3.51189
doi: 10.1002/acn3.51189
pubmed: 32931652
pmcid: 7545592
Ogasawara M, Iida A, Kumutpongpanich T, Ozaki A, Oya Y, Konishi H et al (2020) CGG expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy with neurological manifestations. Acta Neuropathol Commun. 8(1):204. https://doi.org/10.1186/s40478-020-01084-4
doi: 10.1186/s40478-020-01084-4
pubmed: 33239111
pmcid: 7690190
Fang P, Yu Y, Yao S, Chen S, Zhu M, Chen Y et al (2020) Repeat expansion scanning of the NOTCH2NLC gene in patients with multiple system atrophy. Ann Clin Transl Neurol. 7(4):517–26. https://doi.org/10.1002/acn3.51021
doi: 10.1002/acn3.51021
pubmed: 32250060
pmcid: 7187708
Cao L, Yan Y, Zhao G (2021) NOTCH2NLC-related repeat expansion disorders: an expanding group of neurodegenerative disorders. Neurol Sci. https://doi.org/10.1007/s10072-021-05498-3
Alturkustani M, Sharma M, Hammond R, Ang LC (2013) Adult-onset leukodystrophy: review of 3 clinicopathologic phenotypes and a proposed classification. J Neuropathol Exp Neurol 72(11):1090–103. https://doi.org/10.1097/NEN.0000000000000008
doi: 10.1097/NEN.0000000000000008
pubmed: 24128683
Parikh S, Bernard G, Leventer RJ, van der Knaap MS, van Hove J, Pizzino A et al (2015) A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies. Mol Genet Metab 114(4):501–15. https://doi.org/10.1016/j.ymgme.2014.12.434
doi: 10.1016/j.ymgme.2014.12.434
pubmed: 25655951