Adult-onset autosomal dominant leukodystrophy

General Information (adopted from Orphanet):

Synonyms, Signs: PELIZAEUS-MERZBACHER DISEASE, AUTOSOMAL DOMINANT OR LATE-ONSET TYPE, FORMERLY
ADLD
Number of Symptoms 65
OrphanetNr: 99027
OMIM Id: 169500
ICD-10: E75.2
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal dominant
[Orphanet]
Age of onset: Adult onset
[Omim]

Disease classification (adopted from Orphanet):

Parent Diseases: Abnormal eye movements
 -Rare eye disease
 -Rare genetic disease
Leukodystrophy
 -Rare genetic disease
 -Rare neurologic disease
Partial trisomy of the long arm of chromosome 5
 -Rare developmental defect during embryogenesis
 -Rare genetic disease

Symptom Information: Sort by abundance 

1
 (HPO:0000802) Impotence 20 / 7739
2
 (HPO:0002839) Urinary bladder sphincter dysfunction Frequent [Orphanet] 34 / 7739
3
 (HPO:0000079) Abnormality of the urinary system 88 / 7739
4
 (HPO:0100639) Erectile abnormalities Frequent [Orphanet] 15 / 7739
5
 (HPO:0000572) Visual loss Occasional [Orphanet] 272 / 7739
6
 (HPO:0000639) Nystagmus Frequent [Orphanet] 555 / 7739
7
 (HPO:0000365) Hearing impairment Occasional [Orphanet] 539 / 7739
8
 (HPO:0001337) Tremor Frequent [Orphanet] 200 / 7739
9
 (HPO:0001276) Hypertonia Frequent [Orphanet] 317 / 7739
10
 (HPO:0011442) Abnormality of central motor function Very frequent [Orphanet] 76 / 7739
11
 (HPO:0002167) Neurological speech impairment Occasional [Orphanet] 308 / 7739
12
 (HPO:0000751) Personality changes 33 / 7739
13
 (HPO:0001257) Spasticity 251 / 7739
14
 (HPO:0003487) Babinski sign 179 / 7739
15
 (HPO:0002459) Dysautonomia 34 / 7739
16
 (HPO:0001347) Hyperreflexia 363 / 7739
17
 (HPO:0000716) Depression 99 / 7739
18
 (HPO:0002066) Gait ataxia Very frequent [Orphanet] 327 / 7739
19
 (HPO:0100543) Cognitive impairment 230 / 7739
20
 (HPO:0001288) Gait disturbance Frequent [Orphanet] 318 / 7739
21
 (HPO:0001251) Ataxia 413 / 7739
22
 (HPO:0008652) Autonomic erectile dysfunction 3 / 7739
23
 (HPO:0002015) Dysphagia Occasional [Orphanet] 301 / 7739
24
 (HPO:0004926) Orthostatic hypotension due to autonomic dysfunction 2 / 7739
25
 (HPO:0100022) Abnormality of movement Frequent [Orphanet] 129 / 7739
26
 (HPO:0002344) Progressive neurologic deterioration 27 / 7739
27
 (HPO:0007256) Abnormal pyramidal signs 116 / 7739
28
 (HPO:0005341) Autonomic bladder dysfunction 1 / 7739
29
 (HPO:0007262) Symmetric peripheral demyelination 1 / 7739
30
 (HPO:0007024) Pseudobulbar paralysis 7 / 7739
31
 (HPO:0002019) Constipation Frequent [Orphanet] 194 / 7739
32
 (HPO:0007480) Decreased sweating due to autonomic dysfunction 1 / 7739
33
 (HPO:0002615) Hypotension Frequent [Orphanet] 52 / 7739
34
 (HPO:0004370) Abnormality of temperature regulation Occasional [Orphanet] 58 / 7739
35
 (HPO:0003676) Progressive disorder 148 / 7739
36
 (OMIM) Patient cells have increased levels of LMNB1 mRNA and protein 1 / 7739
37
 (OMIM) Leukodystrophy, demyelinating 1 / 7739
38
 (OMIM) Brain imaging shows decreased white matter density 1 / 7739
39
 (OMIM) Neuropathologic findings include leukoencephalopathy, predominantly in the upper corticospinal tract and cerebellar peduncles (initially) 1 / 7739
40
 (HPO:0001317) Abnormality of the cerebellum 36 / 7739
41
 (HPO:0001428) Somatic mutation Very frequent [Orphanet] 100 / 7739
42
 (HPO:0002120) Cerebral cortical atrophy Occasional [Orphanet] 187 / 7739
43
 (HPO:0012758) Neurodevelopmental delay Occasional [Orphanet] 949 / 7739
44
 (HPO:0003581) Adult onset 117 / 7739
45
 (OMIM) White matter lesions in the brainstem may occur 1 / 7739
46
 (OMIM) Oligodendrocytes with foamy cytoplasm 1 / 7739
47
 (HPO:0000006) Autosomal dominant inheritance 2518 / 7739
48
 (OMIM) Abnormal bowel regulation due to autonomic dysfunction 1 / 7739
49
 (HPO:0002415) Leukodystrophy 30 / 7739
50
 (OMIM) Loss of fine motor skills 1 / 7739
51
 (OMIM) Leukoencephalopathy in the frontal and parietal lobes (later) 1 / 7739
52
 (OMIM) Preservation of U fibers 2 / 7739
53
 (OMIM) Lack of inflammatory infiltrate 1 / 7739
54
 (OMIM) Decreased numbers of astrocytes 1 / 7739
55
 (HPO:0006994) Diffuse leukoencephalopathy 1 / 7739
56
 (HPO:0007370) Aplasia/Hypoplasia of the corpus callosum Occasional [Orphanet] 180 / 7739
57
 (OMIM) Hypotrophic brainstem 1 / 7739
58
 (OMIM) Cavitating white matter degeneration 1 / 7739
59
 (HPO:0007371) Corpus callosum atrophy 14 / 7739
60
 (OMIM) Astrocytes show reactive changes 1 / 7739
61
 (OMIM) Abnormal bladder regulation due to autonomic dysfunction 1 / 7739
62
 (HPO:0002171) Gliosis 48 / 7739
63
 (OMIM) Sparing of optic tracts 1 / 7739
64
 (OMIM) Demyelination, symmetric 1 / 7739
65
 (OMIM) Atrophic spinal cord 2 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Autosomal dominant adult-onset demyelinating leukodystrophy is a slowly progressive and fatal disorder that presents in the fourth or fifth decade of life and is characterized clinically by early autonomic abnormalities, pyramidal and cerebellar dysfunction, and symmetric demyelination of ...
Diagnosis OMIM Schuster et al. (2011) found about a 2-fold increased level of LMNB1 protein in white blood cells from 5 patients with genetically confirmed ADLD. LMNB1 mRNA was also increased compared to controls. Schuster et al. (2011) concluded that ...
Clinical Description OMIM Zerbin-Rudin and Peiffer (1964) described a familial disorder similar to Pelizaeus-Merzbacher disease (PMD; 312080) except that it showed later onset and autosomal dominant inheritance rather than X-linked inheritance typical of PMD. The disease was noted to be similar ...
Molecular genetics OMIM Padiath et al. (2006) found duplication of the LMNB1 gene (150340.0001) as the cause of ADLD in affected members of 4 families. One of these was the family described by Eldridge et al. (1984); haplotype analysis suggested that ...