LMNB1-Related Adult-Onset Autosomal Dominant Leukodystrophy Presenting as Movement Disorder: A Case Report and Review of the Literature

Abstract

Adult-onset autosomal dominant leukodystrophy (ADLD) is a lately described rare form of leukodystrophy with only one family report from China. As the only disease associated with increased lamina B1 encoded by LMNB1, ADLDs have different clinical presentations, ranging from autonomic to pyramidal tract and cerebellar ataxia. Here, we report a case of ADLD that presented with positional tremor as the initial symptom. T2-weighted brain MRI showed brain atrophy and diffuse high signal intensity of the cerebral white matter and the brain stem. The precise diagnosis was made by identification of the mutated gene. To the best of our knowledge, this is perhaps the first case report of ADLD presenting as tremor in China.

Cell signaling pathways in autosomal-dominant leukodystrophy (ADLD): the intriguing role of the astrocytes

“…The real prevalence of this ultra-rare pathology remains still uncertain [4] with sporadic new clinical case reports from different geographical areas, suggesting a possible heterogeneity in the first clinical manifestations and signs [5][6][7][8][9][10]. In majority of ADLD cases, the first clinical manifestations are related to autonomic dysfunction from bladder or bowel dysfunction to orthostatic hypotension, temperature dysregulation, and anhidrosis [11][12][13][14][15].…”

“…Autosomal-dominant leukodystrophy (ADLD) is an extremely rare, fatal, and late onset progressive neurological disorder which affects the white matter of the central nervous system (CNS) usually, in the IV or V decade [ 1 – 3 ]. The real prevalence of this ultra-rare pathology remains still uncertain [ 4 ] with sporadic new clinical case reports from different geographical areas, suggesting a possible heterogeneity in the first clinical manifestations and signs [ 5 – 10 ]. In majority of ADLD cases, the first clinical manifestations are related to autonomic dysfunction from bladder or bowel dysfunction to orthostatic hypotension, temperature dysregulation, and anhidrosis [ 11 – 15 ].…”

Dream enactment behavior: review for the clinician

“…[232][233][234][235][236] Finally, there have been a few reports of video polysomnographyconfirmed DEB, mostly RBD, in adults with genetic disorders. These include autosomal dominant leukodystrophy, 237,238 Niemann-Pick disease type C, 239 fatal familial thalamic degeneration, 183 spinocerebellar ataxia (types 2, 3, 31), [240][241][242][243] Wilson disease (12.5%, n = 40). 127 The few cases described make it impossible to estimate the prevalence of DEB.…”

Nuclear Lamins: Key Proteins for Embryonic Development

“…• X-linked recessive disorder, Emerin (STA) mutation [45] • Mutation in Lamin A/C produced by the alternate splicing of LMNA gene [46] Mandibuloacral dysplasia and partial lipodystrophy Homozygous missense mutation, Arg527His, in LMNA gene. Muation in ZMPSTE24 [47] Mandibuloacral dysplasia with type A lipodystrophy (MADA) Homozygous mutation in R527H in the LMNA gene [48] Restrictive dermopathy (RD) Limb Girdle muscular dystrophy type 1B (LGMD1B) Mutation linked to the chromosome 1q11-q21 of LMNA gene [43] Dilated cardiomyopathy (DCM) R89L, 959delT, R337H, S573L mutation in LMNA [52,53] Autosomal recessive axonal Charcot-Marie-Tooth type 2 (CMT2) R298C mutation in lamin A/C [54] Dunnigan type familial partial lipodystrophy (FPLD) R482Q mutation in lamin A/C, mutation in the gene mapped to chromosome 1q21-22 encoding for the LMNA gene [55] Adult autosomal dominant leukodystrophy (movement disorder) Associated with increase or accumulation of lamin B1 [56] Primary microcephaly (neuro-developmental disorder) Heterozygous dominant pathogenic variants in both lamin B1 and lamin B2 [57] Progressive myoclonus epilepsy including the early identification of ataxia Rare and novel homozygous missense p.His157Tyr mutation in the alpha-helical rod of the lamin B2 protein [58] Acquired partial lipodystrophy (APL) Mutation in the LMNB2 gene on 19p13.3 might be the cause of this disease [59] Interestingly, although a number of mutations in the LMNA gene have been described (see Introduction), practically no laminopathies linked to B-type lamins (LMNB1/LMNB2 mutations) have been reported to date with very few exceptions presented in Table 1. For this reason, the general notion is that mutations in the genes encoding for B-type lamins, or their loss, are developmentally lethal and that lamins B1/B2 might be essential at the cellular level, i.e., necessary for cell viability.…”