MCID: LKD017
MIFTS: 39

Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Fetal diseases

Aliases & Classifications for Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia...

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism:

Name: Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism 57 75 13
Leukodystrophy with Oligodontia 12 53 59 75
Dentoleukoencephalopathy 12 53 59
Hld7 57 12 75
Hypomyelinating Leukodystrophy 7 with or Without Oligodontia and-or Hypogonadotropic Hypogonadism 12 15
Leukodystrophy, Hypomyelinating, with Hypodontia and Hypogonadotropic Hypogonadism 57 73
Hypomyelination-Cerebellar Atrophy-Hypoplasia of the Corpus Callosum Syndrome 12 59
Tremor-Ataxia-Central Hypomyelination Syndrome 12 59
Tach Syndrome 12 59
Addh 57 75
Leukodystrophy Hypomyelinating with Hypodontia and Hypogonadotropic Hypogonadism 4h Syndrome 75
Hypomyelinating Leukodystrophy-Ataxia-Hypodontia-Hypomyelination Syndrome 59
Leukoencephalopathy, Hypomyelinating, with Ataxia and Delayed Dentition 57
Ataxia-Delayed Dentition-Hypomyelination Syndrome; Odontoleukodystrophy 12
Leukoencephalopathy Hypomyelinating with Ataxia and Delayed Dentition 75
Leukoencephalopathy-Ataxia-Hypodontia-Hypomyelination Syndrome 12
Ataxia, Delayed Dentition, and Hypomyelination; Addh 57
Ataxia-Delayed Dentition-Hypomyelination Syndrome 59
Leukodystrophy, Dysmyelinating, with Oligodontia 73
Ataxia, Delayed Dentition, and Hypomyelination 57
Dentoleukoencephalopathy, Autosomal Recessive 53
Ataxia Delayed Dentition and Hypomyelination 75
Tremor-Ataxia with Central Hypomyelination 75
Attention Deficit Hyperactivity Disorder 73
Odontoleukodystrophy 59
4h Syndrome 57
Tach 75

Characteristics:

Orphanet epidemiological data:

59
hypomyelinating leukodystrophy-ataxia-hypodontia-hypomyelination syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;
tremor-ataxia-central hypomyelination syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy; Age of death: adult;
hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent;
odontoleukodystrophy
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable phenotype
progressive disorder
onset in childhood (range 1 to 12 years)
many patients become wheelchair-bound by second or third decade


HPO:

32
leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism:
Onset and clinical course phenotypic variability progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia...

OMIM : 57 Hypomyelinating leukodystrophy-7 is an autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive motor decline manifest as spasticity, ataxia, tremor, and cerebellar signs, as well as mild cognitive regression. Other features may include hypodontia or oligodontia and hypogonadotropic hypogonadism. There is considerable inter- and intrafamilial variability (summary by Bernard et al., 2011). See also HLD8 (614381), which has similar features and is caused by mutation in the POLR3B gene (614366) on chromosome 12q23. The POLR3A and POLR3B genes encode the 2 largest subunits of RNA polymerase III. For a general phenotypic description and a discussion of genetic heterogeneity of hypomyelinating leukodystrophy, see 312080. (607694)

MalaCards based summary : Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism, also known as leukodystrophy with oligodontia, is related to pol iii-related leukodystrophies and leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, and has symptoms including back pain, headache and pain. An important gene associated with Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism is POLR3A (RNA Polymerase III Subunit A). Affiliated tissues include eye and brain, and related phenotypes are nystagmus and spasticity

Disease Ontology : 12 A hypomyelinating leukodystrophy characterized by autosomal recessive inheritance of hildhood onset of progressive motor decline manifest as spasticity, ataxia, tremor, and cerebellar signs, as well as mild cognitive regression that has material basis in homozygous or compound heterozygous mutation in the POLR3A gene on chromosome 10q22.

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 77295Disease definitionLeukodystrophy with oligodontia is characterised by progressive ataxia beginning during infancy, a pyramidal syndrome and dental agenesis. The syndrome has been described in four children born to consanguineous parents. The mode of transmission is autosomal recessive.Visit the Orphanet disease page for more resources.

UniProtKB/Swiss-Prot : 75 Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism: An autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive motor decline manifest as spasticity, ataxia, tremor, and cerebellar signs, as well as mild cognitive regression. Other features may include hypodontia or oligodontia and hypogonadotropic hypogonadism. There is considerable inter- and intrafamilial variability.

Related Diseases for Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia...

Diseases related to Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 pol iii-related leukodystrophies 11.6
2 leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism 11.0
3 leukodystrophy, hypomyelinating, 3 9.2 AIMP1 POLR3A
4 hypomyelinating leukodystrophy 9.0 AIMP1 POLR3A

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia...

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus
myopia
optic atrophy (in some patients)
abnormal smooth pursuit
vertical gaze limitation

Growth Height:
short stature

Abdomen Gastrointestinal:
dysphagia (in some patients)

Genitourinary Bladder:
bladder dysfunction (rare)

Endocrine Features:
delayed puberty (in most patients)
hypogonadotropic hypogonadism (in most patients)

Neurologic Central Nervous System:
spasticity
dysarthria
hyperreflexia
dysmetria
dystonia
more
Head And Neck Teeth:
delayed dentition
delayed eruption of the upper median incisors
hypodontia (in most patients)
oligodontia (in most patients)

Head And Neck Mouth:
drooling (in some patients)

Neurologic Peripheral Nervous System:
peripheral neuropathy (some patients)
decreased vibratory and positional sense (some patients)


Clinical features from OMIM:

607694

Human phenotypes related to Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism:

59 32 (show all 44)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 59 32 occasional (7.5%) Frequent (79-30%) HP:0000639
2 spasticity 59 32 Frequent (79-30%) HP:0001257
3 hyperreflexia 59 32 frequent (33%) Frequent (79-30%) HP:0001347
4 dysphagia 59 32 frequent (33%) Frequent (79-30%) HP:0002015
5 developmental regression 59 32 frequent (33%) Frequent (79-30%) HP:0002376
6 global developmental delay 59 32 frequent (33%) Frequent (79-30%) HP:0001263
7 optic atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0000648
8 short stature 59 32 frequent (33%) Frequent (79-30%) HP:0004322
9 delayed puberty 59 32 hallmark (90%) Frequent (79-30%) HP:0000823
10 intellectual disability, mild 59 32 frequent (33%) Frequent (79-30%) HP:0001256
11 peripheral neuropathy 59 32 occasional (7.5%) Occasional (29-5%) HP:0009830
12 delayed eruption of teeth 59 32 frequent (33%) Frequent (79-30%) HP:0000684
13 myopia 59 32 frequent (33%) Frequent (79-30%) HP:0000545
14 babinski sign 59 32 frequent (33%) Frequent (79-30%) HP:0003487
15 dysmetria 59 32 frequent (33%) Frequent (79-30%) HP:0001310
16 intention tremor 59 32 frequent (33%) Frequent (79-30%) HP:0002080
17 dystonia 59 32 frequent (33%) Frequent (79-30%) HP:0001332
18 hypogonadotrophic hypogonadism 59 32 frequent (33%) Frequent (79-30%) HP:0000044
19 cerebral cortical atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0002120
20 cerebellar hypoplasia 59 32 frequent (33%) Frequent (79-30%) HP:0001321
21 deeply set eye 59 32 very rare (1%) Very rare (<4-1%) HP:0000490
22 clumsiness 59 32 frequent (33%) Frequent (79-30%) HP:0002312
23 hypodontia 59 32 frequent (33%) Frequent (79-30%) HP:0000668
24 postural tremor 59 32 frequent (33%) Frequent (79-30%) HP:0002174
25 impaired vibration sensation in the lower limbs 59 32 occasional (7.5%) Occasional (29-5%) HP:0002166
26 hypoplasia of the corpus callosum 59 32 frequent (33%) Frequent (79-30%) HP:0002079
27 leukodystrophy 59 32 frequent (33%) Frequent (79-30%) HP:0002415
28 drooling 59 32 occasional (7.5%) Occasional (29-5%) HP:0002307
29 vertical supranuclear gaze palsy 59 32 frequent (33%) Frequent (79-30%) HP:0000511
30 cns hypomyelination 59 32 frequent (33%) Frequent (79-30%) HP:0003429
31 oligodontia 59 32 frequent (33%) Frequent (79-30%) HP:0000677
32 spastic dysarthria 59 32 frequent (33%) Frequent (79-30%) HP:0002464
33 abnormality of ocular smooth pursuit 59 32 frequent (33%) Frequent (79-30%) HP:0000617
34 abnormality of the basal ganglia 59 32 frequent (33%) Frequent (79-30%) HP:0002134
35 autonomic bladder dysfunction 59 32 frequent (33%) Frequent (79-30%) HP:0005341
36 impaired distal proprioception 59 32 occasional (7.5%) Occasional (29-5%) HP:0006858
37 positive romberg sign 59 32 frequent (33%) Frequent (79-30%) HP:0002403
38 high myoinositol in brain by mrs 59 32 frequent (33%) Frequent (79-30%) HP:0025460
39 focal seizures, afebril 59 32 very rare (1%) Very rare (<4-1%) HP:0040168
40 ataxia 59 Frequent (79-30%)
41 dysarthria 32 HP:0001260
42 cerebellar atrophy 32 HP:0001272
43 abnormal upper motor neuron morphology 32 HP:0002127
44 upper motor neuron dysfunction 59 Frequent (79-30%)

UMLS symptoms related to Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism:


back pain, headache, pain, sciatica, seizures, syncope, tremor, chronic pain, vertigo/dizziness, sleeplessness, ataxia, cerebellar ataxia, muscle spasticity, static tremor, cerebellar signs, upper motor neuron signs

Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia...

Genetic Tests for Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia...

Anatomical Context for Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia...

MalaCards organs/tissues related to Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism:

41
Eye, Brain

Publications for Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia...

Articles related to Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism:

# Title Authors Year
1
Tremor-ataxia with central hypomyelination (TACH): dystonia as a new clinical feature. ( 23208740 )
2012
2
Tremor-ataxia with central hypomyelination (TACH) leukodystrophy maps to chromosome 10q22.3-10q23.31. ( 20640464 )
2010

Variations for Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia...

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism:

75 (show all 15)
# Symbol AA change Variation ID SNP ID
1 POLR3A p.Asp372Asn VAR_066516 rs267608673
2 POLR3A p.Phe558Leu VAR_066517 rs267608668
3 POLR3A p.Ser636Tyr VAR_066518 rs267608676
4 POLR3A p.Gly672Glu VAR_066519 rs267608670
5 POLR3A p.Cys724Tyr VAR_066520 rs267608679
6 POLR3A p.Asn775Ile VAR_066521 rs267608672
7 POLR3A p.Met852Val VAR_066522 rs267608671
8 POLR3A p.Arg1005Cys VAR_066523 rs267608682
9 POLR3A p.Ile897Asn VAR_067004 rs267608681
10 POLR3A p.Pro91Leu VAR_072338
11 POLR3A p.Trp310Cys VAR_072339
12 POLR3A p.Ala387Gly VAR_072340
13 POLR3A p.Ser602Arg VAR_072341 rs762708292
14 POLR3A p.Ile804Thr VAR_072342
15 POLR3A p.Glu1261Lys VAR_072343 rs371703979

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism:

6
(show all 40)
# Gene Variation Type Significance SNP ID Assembly Location
1 POLR3A NM_007055.3(POLR3A): c.2015G> A (p.Gly672Glu) single nucleotide variant Pathogenic rs267608670 GRCh37 Chromosome 10, 79767519: 79767519
2 POLR3A NM_007055.3(POLR3A): c.2015G> A (p.Gly672Glu) single nucleotide variant Pathogenic rs267608670 GRCh38 Chromosome 10, 78007761: 78007761
3 POLR3A NM_007055.3(POLR3A): c.1909+18G> A single nucleotide variant Pathogenic rs267608677 GRCh37 Chromosome 10, 79769277: 79769277
4 POLR3A NM_007055.3(POLR3A): c.1909+18G> A single nucleotide variant Pathogenic rs267608677 GRCh38 Chromosome 10, 78009519: 78009519
5 POLR3A NM_007055.3(POLR3A): c.2554A> G (p.Met852Val) single nucleotide variant Likely pathogenic rs267608671 GRCh37 Chromosome 10, 79759801: 79759801
6 POLR3A NM_007055.3(POLR3A): c.2554A> G (p.Met852Val) single nucleotide variant Likely pathogenic rs267608671 GRCh38 Chromosome 10, 78000043: 78000043
7 POLR3A NM_007055.3(POLR3A): c.2617-1G> A single nucleotide variant Pathogenic rs181087667 GRCh37 Chromosome 10, 79753126: 79753126
8 POLR3A NM_007055.3(POLR3A): c.2617-1G> A single nucleotide variant Pathogenic rs181087667 GRCh38 Chromosome 10, 77993368: 77993368
9 POLR3A NM_007055.3(POLR3A): c.418C> T (p.Arg140Ter) single nucleotide variant Pathogenic rs267608678 GRCh37 Chromosome 10, 79784801: 79784801
10 POLR3A NM_007055.3(POLR3A): c.418C> T (p.Arg140Ter) single nucleotide variant Pathogenic rs267608678 GRCh38 Chromosome 10, 78025043: 78025043
11 POLR3A NM_007055.3(POLR3A): c.2690T> A (p.Ile897Asn) single nucleotide variant Pathogenic rs267608681 GRCh37 Chromosome 10, 79753052: 79753052
12 POLR3A NM_007055.3(POLR3A): c.2690T> A (p.Ile897Asn) single nucleotide variant Pathogenic rs267608681 GRCh38 Chromosome 10, 77993294: 77993294
13 POLR3A NM_007055.3(POLR3A): c.3013C> T (p.Arg1005Cys) single nucleotide variant Pathogenic rs267608682 GRCh37 Chromosome 10, 79745719: 79745719
14 POLR3A NM_007055.3(POLR3A): c.3013C> T (p.Arg1005Cys) single nucleotide variant Pathogenic rs267608682 GRCh38 Chromosome 10, 77985961: 77985961
15 POLR3A NM_007055.3(POLR3A): c.1114G> A (p.Asp372Asn) single nucleotide variant Pathogenic rs267608673 GRCh37 Chromosome 10, 79781375: 79781375
16 POLR3A NM_007055.3(POLR3A): c.1114G> A (p.Asp372Asn) single nucleotide variant Pathogenic rs267608673 GRCh38 Chromosome 10, 78021617: 78021617
17 POLR3A NM_007055.3(POLR3A): c.1674C> G (p.Phe558Leu) single nucleotide variant Pathogenic rs267608668 GRCh37 Chromosome 10, 79769718: 79769718
18 POLR3A NM_007055.3(POLR3A): c.1674C> G (p.Phe558Leu) single nucleotide variant Pathogenic rs267608668 GRCh38 Chromosome 10, 78009960: 78009960
19 POLR3A NM_007055.3(POLR3A): c.1907C> A (p.Ser636Tyr) single nucleotide variant Pathogenic rs267608676 GRCh37 Chromosome 10, 79769297: 79769297
20 POLR3A NM_007055.3(POLR3A): c.1907C> A (p.Ser636Tyr) single nucleotide variant Pathogenic rs267608676 GRCh38 Chromosome 10, 78009539: 78009539
21 POLR3A NM_007055.3(POLR3A): c.2171G> A (p.Cys724Tyr) single nucleotide variant Pathogenic rs267608679 GRCh37 Chromosome 10, 79764550: 79764550
22 POLR3A NM_007055.3(POLR3A): c.2171G> A (p.Cys724Tyr) single nucleotide variant Pathogenic rs267608679 GRCh38 Chromosome 10, 78004792: 78004792
23 POLR3A NM_007055.3(POLR3A): c.2324A> T (p.Asn775Ile) single nucleotide variant Pathogenic rs267608672 GRCh37 Chromosome 10, 79761990: 79761990
24 POLR3A NM_007055.3(POLR3A): c.2324A> T (p.Asn775Ile) single nucleotide variant Pathogenic rs267608672 GRCh38 Chromosome 10, 78002232: 78002232
25 POLR3A NM_007055.3(POLR3A): c.2830G> T (p.Glu944Ter) single nucleotide variant Pathogenic rs267608674 GRCh37 Chromosome 10, 79750883: 79750883
26 POLR3A NM_007055.3(POLR3A): c.2830G> T (p.Glu944Ter) single nucleotide variant Pathogenic rs267608674 GRCh38 Chromosome 10, 77991125: 77991125
27 POLR3A NM_007055.3(POLR3A): c.3014G> A (p.Arg1005His) single nucleotide variant Pathogenic rs200118797 GRCh37 Chromosome 10, 79745718: 79745718
28 POLR3A NM_007055.3(POLR3A): c.3014G> A (p.Arg1005His) single nucleotide variant Pathogenic rs200118797 GRCh38 Chromosome 10, 77985960: 77985960
29 POLR3A NM_007055.3(POLR3A): c.3742_3743insACC (p.Ser1248delinsTyrPro) insertion Pathogenic rs267608669 GRCh37 Chromosome 10, 79741928: 79741929
30 POLR3A NM_007055.3(POLR3A): c.3742_3743insACC (p.Ser1248delinsTyrPro) insertion Pathogenic rs267608669 GRCh38 Chromosome 10, 77982170: 77982171
31 POLR3A NM_007055.3(POLR3A): c.3991G> A (p.Ala1331Thr) single nucleotide variant Pathogenic rs267608680 GRCh37 Chromosome 10, 79739932: 79739932
32 POLR3A NM_007055.3(POLR3A): c.3991G> A (p.Ala1331Thr) single nucleotide variant Pathogenic rs267608680 GRCh38 Chromosome 10, 77980174: 77980174
33 POLR3A NM_007055.3(POLR3A): c.4006C> T (p.Gln1336Ter) single nucleotide variant Pathogenic rs267608675 GRCh37 Chromosome 10, 79739917: 79739917
34 POLR3A NM_007055.3(POLR3A): c.4006C> T (p.Gln1336Ter) single nucleotide variant Pathogenic rs267608675 GRCh38 Chromosome 10, 77980159: 77980159
35 POLR3A NM_007055.3(POLR3A): c.3436G> A (p.Ala1146Thr) single nucleotide variant Uncertain significance rs41274600 GRCh38 Chromosome 10, 77982811: 77982811
36 POLR3A NM_007055.3(POLR3A): c.3436G> A (p.Ala1146Thr) single nucleotide variant Uncertain significance rs41274600 GRCh37 Chromosome 10, 79742569: 79742569
37 POLR3A NM_007055.3(POLR3A): c.367_369delAAG (p.Lys123del) deletion no interpretation for the single variant rs780755978 GRCh38 Chromosome 10, 78025092: 78025094
38 POLR3A NM_007055.3(POLR3A): c.367_369delAAG (p.Lys123del) deletion no interpretation for the single variant rs780755978 GRCh37 Chromosome 10, 79784850: 79784852
39 POLR3A NM_007055.3(POLR3A): c.3243-1G> A single nucleotide variant Pathogenic GRCh38 Chromosome 10, 77984299: 77984299
40 POLR3A NM_007055.3(POLR3A): c.3243-1G> A single nucleotide variant Pathogenic GRCh37 Chromosome 10, 79744057: 79744057

Expression for Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia...

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism.

Pathways for Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia...

GO Terms for Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia...

Biological processes related to Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia and/or Hypogonadotropic Hypogonadism according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 defense response to virus GO:0051607 8.62 AIMP1 POLR3A

Sources for Leukodystrophy, Hypomyelinating, 7, with or Without Oligodontia...

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