HMLR1
MCID: HML047
MIFTS: 38

Heimler Syndrome 1 (HMLR1)

Categories: Ear diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Oral diseases, Rare diseases, Skin diseases

Aliases & Classifications for Heimler Syndrome 1

MalaCards integrated aliases for Heimler Syndrome 1:

Name: Heimler Syndrome 1 57 12 73
Deafness Enamel Hypoplasia Nail Defects 20 73 29 6 71
Sensorineural Hearing Loss, Enamel Hypoplasia, and Nail Abnormalities 20 73
Hearing Loss, Sensorineural, with Enamel Hypoplasia and Nail Defects 57 73
Deafness-Enamel Hypoplasia-Nail Defects Syndrome 12 58
Peroxisome Biogenesis Disorder 1c 57 73
Heimler Syndrome 20 58
Hmlr1 57 73
Pbd1c 57 73
Bilateral Sensorineural Hearing Loss, Enamel Hypoplasia and Nail Defects 20
Hearing Loss-Enamel Hypoplasia-Nail Defects Syndrome 58
Peroxisome Biogenesis Disorder 1c; Pbd1c 57
Peroxisomal Biogenesis Disorder 1c 12
Heimler Syndrome, Type 1 39

Characteristics:

Orphanet epidemiological data:

58
deafness-enamel hypoplasia-nail defects syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive


HPO:

31
heimler syndrome 1:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare otorhinolaryngological diseases
Rare skin diseases
Developmental anomalies during embryogenesis
Rare odontological diseases


Summaries for Heimler Syndrome 1

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 3220DefinitionDeafness-enamel hypoplasia-nail defects syndrome is characterised by sensorineural hearing loss, generalised enamel hypoplasia of the permanent dentition with normal primary dentition, and nail defects (Beau's lines and leukonychia). Less than 10 patients have been described so far. Transmission is autosomal recessive.Visit the Orphanet disease page for more resources.

MalaCards based summary : Heimler Syndrome 1, also known as deafness enamel hypoplasia nail defects, is related to peroxisome biogenesis disorder 1a and amelogenesis imperfecta. An important gene associated with Heimler Syndrome 1 is PEX1 (Peroxisomal Biogenesis Factor 1), and among its related pathways/superpathways is Peroxisome. Related phenotypes are intellectual disability and diabetes mellitus

Disease Ontology : 12 A peroxisomal biogenesis disorder that is characterised by sensorineural hearing loss, generalised enamel hypoplasia of the permanent dentition with normal primary dentition, and nail defects and has material basis in homozygous or compound heterozygous mutations in the PEX1 gene on chromosome 7q21.

OMIM® : 57 Heimler syndrome-1 (HMLR1), which represents the mildest end of the peroxisomal biogenesis disorder spectrum (see PBD1A, 214100), is a rare autosomal recessive disorder characterized by sensorineural hearing loss, enamel hyoplasia of the secondary dentition, and nail abnormalities (Ratbi et al., 2015). (234580) (Updated 05-Mar-2021)

UniProtKB/Swiss-Prot : 73 Heimler syndrome 1: A form of Heimler syndrome, a very mild peroxisome biogenesis disorder characterized by sensorineural hearing loss, amelogenesis imperfecta resulting in enamel hyoplasia of the secondary dentition, nail defects, and occasional or late-onset retinal pigmentation abnormalities.

Wikipedia : 74 Heimler syndrome is a rare autosomal recessive condition characterized by sensorineural hearing loss,... more...

Related Diseases for Heimler Syndrome 1

Graphical network of the top 20 diseases related to Heimler Syndrome 1:



Diseases related to Heimler Syndrome 1

Symptoms & Phenotypes for Heimler Syndrome 1

Human phenotypes related to Heimler Syndrome 1:

58 31 (show all 39)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 diabetes mellitus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000819
3 sensorineural hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000407
4 abnormal fingernail morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0001231
5 taurodontia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000679
6 abnormality of dental enamel 58 31 hallmark (90%) Very frequent (99-80%) HP:0000682
7 abnormal hair quantity 58 31 hallmark (90%) Very frequent (99-80%) HP:0011362
8 abnormal toenail morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0008388
9 hypogonadism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000135
10 abnormality of nail color 58 31 hallmark (90%) Very frequent (99-80%) HP:0100643
11 pili torti 58 31 hallmark (90%) Very frequent (99-80%) HP:0003777
12 external genital hypoplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0003241
13 thin eyebrow 58 31 hallmark (90%) Very frequent (99-80%) HP:0045074
14 abnormal nasolacrimal system morphology 31 hallmark (90%) HP:0000614
15 abnormal eyelid morphology 31 hallmark (90%) HP:0000492
16 short stature 58 31 frequent (33%) Frequent (79-30%) HP:0004322
17 primary amenorrhea 58 31 frequent (33%) Frequent (79-30%) HP:0000786
18 arrhythmia 58 31 frequent (33%) Frequent (79-30%) HP:0011675
19 round face 58 31 frequent (33%) Frequent (79-30%) HP:0000311
20 large hands 58 31 frequent (33%) Frequent (79-30%) HP:0001176
21 cerebral calcification 58 31 occasional (7.5%) Occasional (29-5%) HP:0002514
22 delayed skeletal maturation 58 31 occasional (7.5%) Occasional (29-5%) HP:0002750
23 ichthyosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0008064
24 high anterior hairline 58 31 occasional (7.5%) Occasional (29-5%) HP:0009890
25 sensory neuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000763
26 hyporeflexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001265
27 camptodactyly of finger 58 31 occasional (7.5%) Occasional (29-5%) HP:0100490
28 acanthosis nigricans 58 31 occasional (7.5%) Occasional (29-5%) HP:0000956
29 muscle flaccidity 58 31 occasional (7.5%) Occasional (29-5%) HP:0010547
30 macular dystrophy 31 occasional (7.5%) HP:0007754
31 hearing impairment 58 Very frequent (99-80%)
32 abnormality of the dentition 58 Very frequent (99-80%)
33 abnormality of the eyelid 58 Very frequent (99-80%)
34 peripheral neuropathy 58 Occasional (29-5%)
35 abnormality of the eyebrow 58 Very frequent (99-80%)
36 abnormality of the nasolacrimal system 58 Very frequent (99-80%)
37 amelogenesis imperfecta 31 HP:0000705
38 hypoplasia of dental enamel 31 HP:0006297
39 leukonychia 31 HP:0001820

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Head And Neck Ears:
sensorineural hearing loss

Head And Neck Teeth:
normal primary teeth
amelogenesis imperfecta (secondary teeth)

Head And Neck Eyes:
retinal pigmentation abnormalities (in some patients)
macular dystrophy (rare)

Skin Nails Hair Nails:
beau's lines (fingernails and toenails)
punctate leukonychia

Clinical features from OMIM®:

234580 (Updated 05-Mar-2021)

Drugs & Therapeutics for Heimler Syndrome 1

Search Clinical Trials , NIH Clinical Center for Heimler Syndrome 1

Genetic Tests for Heimler Syndrome 1

Genetic tests related to Heimler Syndrome 1:

# Genetic test Affiliating Genes
1 Deafness Enamel Hypoplasia Nail Defects 29 PEX1

Anatomical Context for Heimler Syndrome 1

Publications for Heimler Syndrome 1

Articles related to Heimler Syndrome 1:

(show all 13)
# Title Authors PMID Year
1
Sensorineural hearing loss, enamel hypoplasia, and nail abnormalities in sibs. 61 6 57
2063923 1991
2
Heimler Syndrome Is Caused by Hypomorphic Mutations in the Peroxisome-Biogenesis Genes PEX1 and PEX6. 57 6
26387595 2015
3
PEX6 is Expressed in Photoreceptor Cilia and Mutated in Deafblindness with Enamel Dysplasia and Microcephaly. 6
26593283 2016
4
Spectrum of PEX6 mutations in Zellweger syndrome spectrum patients. 6
19877282 2010
5
Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders. 6
19105186 2009
6
Peroxisome biogenesis disorders. 6
17055079 2006
7
Sensorineural deafness, enamel abnormalities and nail abnormalities: a case report of Heimler syndrome in identical twin girls. 6
16530715 2006
8
The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum. 6
15542397 2004
9
Sensorineural hearing loss and enamel hypoplasia with subtle nail findings: another family with Heimler's syndrome. 57
12514367 2003
10
Amelogenesis imperfecta, sensorineural hearing loss, and Beau's lines, a second case report of Heimler's syndrome. 57
10636745 1999
11
Identification of a common PEX1 mutation in Zellweger syndrome. 6
10447258 1999
12
Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders. 6
9398847 1997
13
Mutations in the 70K peroxisomal membrane protein gene in Zellweger syndrome. 6
1301993 1992

Variations for Heimler Syndrome 1

ClinVar genetic disease variations for Heimler Syndrome 1:

6 (show all 40)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GATAD1 NM_000466.3(PEX1):c.3750G>A (p.Trp1250Ter) SNV Pathogenic 217431 rs863225085 7:92118624-92118624 7:92489310-92489310
2 PEX1 NM_000466.3(PEX1):c.1792del (p.Thr598fs) Deletion Pathogenic 224324 rs886037783 7:92136319-92136319 7:92507005-92507005
3 PEX1 NM_000466.3(PEX1):c.1742G>C (p.Arg581Pro) SNV Pathogenic 217429 rs370483961 7:92136369-92136369 7:92507055-92507055
4 PEX6 NM_000287.4(PEX6):c.1841del (p.Leu614fs) Deletion Pathogenic 217426 rs863225083 6:42935149-42935149 6:42967411-42967411
5 PEX1 NM_000466.3(PEX1):c.2114T>G (p.Leu705Trp) SNV Pathogenic 217428 rs863225084 7:92132467-92132467 7:92503153-92503153
6 PEX6 NM_000287.4(PEX6):c.821C>T (p.Pro274Leu) SNV Pathogenic 217424 rs61753219 6:42946068-42946068 6:42978330-42978330
7 PEX6 NM_000287.4(PEX6):c.1802G>A (p.Arg601Gln) SNV Pathogenic 198709 rs34324426 6:42935188-42935188 6:42967450-42967450
8 PEX6 NM_000287.4(PEX6):c.1930C>T (p.Arg644Trp) SNV Pathogenic 217425 rs769896492 6:42934551-42934551 6:42966813-42966813
9 PEX1 NM_000466.3(PEX1):c.1239+1G>T SNV Pathogenic 217430 rs756876301 7:92146589-92146589 7:92517275-92517275
10 PEX6 NM_000287.4(PEX6):c.296G>T (p.Arg99Leu) SNV Pathogenic 224320 rs886037781 6:42946593-42946593 6:42978855-42978855
11 PEX6 NM_000287.4(PEX6):c.1715C>T (p.Thr572Ile) SNV Pathogenic 224323 rs61753224 6:42935275-42935275 6:42967537-42967537
12 PEX6 NM_000287.4(PEX6):c.654C>G (p.Phe218Leu) SNV Pathogenic 224318 rs886037779 6:42946235-42946235 6:42978497-42978497
13 PEX6 NM_000287.4(PEX6):c.1314_1321del (p.Glu439fs) Deletion Pathogenic 224321 rs267608216 6:42937452-42937459 6:42969714-42969721
14 PEX6 NM_000287.4(PEX6):c.275T>G (p.Val92Gly) SNV Pathogenic 224319 rs886037780 6:42946614-42946614 6:42978876-42978876
15 GATAD1 NM_000466.3(PEX1):c.2966T>C (p.Ile989Thr) SNV Pathogenic 224325 rs61750427 7:92123671-92123671 7:92494357-92494357
16 PEX6 NM_000287.4(PEX6):c.2714G>T (p.Cys905Phe) SNV Pathogenic 224322 rs886037782 6:42932620-42932620 6:42964882-42964882
17 PEX6 NM_000287.4(PEX6):c.2440C>T (p.Arg814Ter) SNV Pathogenic 194165 rs267608241 6:42933450-42933450 6:42965712-42965712
18 PEX6 NM_000287.4(PEX6):c.1802G>A (p.Arg601Gln) SNV Pathogenic 198709 rs34324426 6:42935188-42935188 6:42967450-42967450
19 PEX6 NM_000287.4(PEX6):c.1238G>T (p.Gly413Val) SNV Pathogenic 556748 rs1554127531 6:42937535-42937535 6:42969797-42969797
20 PEX1 NM_000466.3(PEX1):c.2097dup (p.Ile700fs) Duplication Pathogenic 7519 rs61750415 7:92132483-92132484 7:92503169-92503170
21 PEX1 NM_000466.3(PEX1):c.2528G>A (p.Gly843Asp) SNV Pathogenic 7516 rs61750420 7:92130876-92130876 7:92501562-92501562
22 PEX1 NM_000466.3(PEX1):c.2528G>A (p.Gly843Asp) SNV Pathogenic 7516 rs61750420 7:92130876-92130876 7:92501562-92501562
23 PEX1 NM_000466.3(PEX1):c.2097dup (p.Ile700fs) Duplication Pathogenic 7519 rs61750415 7:92132483-92132484 7:92503169-92503170
24 GATAD1 NM_000466.3(PEX1):c.3379dup (p.Arg1127fs) Duplication Pathogenic 203390 rs794729652 7:92120644-92120645 7:92491330-92491331
25 PEX6 NM_000287.4(PEX6):c.386A>T (p.Glu129Val) SNV Likely pathogenic 625158 rs1561831003 6:42946503-42946503 6:42978765-42978765
26 GATAD1 NM_000466.3(PEX1):c.2992C>T (p.Arg998Ter) SNV Likely pathogenic 495880 rs61750428 7:92123645-92123645 7:92494331-92494331
27 PEX6 NM_000287.4(PEX6):c.2300+2T>C SNV Likely pathogenic 804456 rs1581760028 6:42933978-42933978 6:42966240-42966240
28 PEX1 NM_000466.3(PEX1):c.1991T>C (p.Leu664Pro) SNV Likely pathogenic 7517 rs121434455 7:92134126-92134126 7:92504812-92504812
29 GATAD1 NM_000466.3(PEX1):c.2922del (p.Leu974fs) Deletion Likely pathogenic 371696 rs762324548 7:92123805-92123805 7:92494491-92494491
30 PEX6 NM_000287.4(PEX6):c.719C>G (p.Ala240Gly) SNV Uncertain significance 288056 rs372269200 6:42946170-42946170 6:42978432-42978432
31 GATAD1 NM_000466.3(PEX1):c.3503A>G (p.Asp1168Gly) SNV Uncertain significance 282718 rs182452430 7:92119161-92119161 7:92489847-92489847
32 PEX1 NM_000466.3(PEX1):c.2750C>T (p.Ala917Val) SNV Uncertain significance 288721 rs371327573 7:92126060-92126060 7:92496746-92496746
33 PEX1 NM_000466.3(PEX1):c.1249G>A (p.Asp417Asn) SNV Uncertain significance 498412 rs143273433 7:92143272-92143272 7:92513958-92513958
34 PEX1 NM_000466.3(PEX1):c.665C>T (p.Thr222Ile) SNV Uncertain significance 197673 rs773922257 7:92147164-92147164 7:92517850-92517850
35 PEX1 NM_000466.3(PEX1):c.254G>A (p.Gly85Glu) SNV Uncertain significance 502318 rs771224088 7:92151435-92151435 7:92522121-92522121
36 PEX1 NM_000466.3(PEX1):c.2200G>A (p.Val734Ile) SNV Uncertain significance 971689 7:92132381-92132381 7:92503067-92503067
37 PEX6 NM_000287.4(PEX6):c.1718C>T (p.Thr573Ile) SNV Uncertain significance 356795 rs140769712 6:42935272-42935272 6:42967534-42967534
38 GATAD1 NM_000466.3(PEX1):c.3756T>A (p.Asn1252Lys) SNV Uncertain significance 548004 rs553001596 7:92118618-92118618 7:92489304-92489304
39 GATAD1 NM_000466.3(PEX1):c.2876G>C (p.Arg959Pro) SNV Uncertain significance 587523 rs773206107 7:92123851-92123851 7:92494537-92494537
40 GATAD1 NM_000466.3(PEX1):c.3373A>T (p.Met1125Leu) SNV Likely benign 360915 rs142994610 7:92120651-92120651 7:92491337-92491337

UniProtKB/Swiss-Prot genetic disease variations for Heimler Syndrome 1:

73
# Symbol AA change Variation ID SNP ID
1 PEX1 p.Arg581Pro VAR_074108 rs370483961
2 PEX1 p.Leu705Trp VAR_074109 rs863225084
3 PEX1 p.Ile989Thr VAR_077503 rs61750427

Expression for Heimler Syndrome 1

Search GEO for disease gene expression data for Heimler Syndrome 1.

Pathways for Heimler Syndrome 1

Pathways related to Heimler Syndrome 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.54 PEX6 PEX1

GO Terms for Heimler Syndrome 1

Cellular components related to Heimler Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 peroxisome GO:0005777 8.96 PEX6 PEX1
2 peroxisomal membrane GO:0005778 8.62 PEX6 PEX1

Biological processes related to Heimler Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein targeting to peroxisome GO:0006625 9.16 PEX6 PEX1
2 peroxisome organization GO:0007031 8.96 PEX6 PEX1
3 protein import into peroxisome matrix GO:0016558 8.62 PEX6 PEX1

Molecular functions related to Heimler Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein-containing complex binding GO:0044877 9.16 PEX6 PEX1
2 ATPase activity GO:0016887 8.96 PEX6 PEX1
3 protein C-terminus binding GO:0008022 8.62 PEX6 PEX1

Sources for Heimler Syndrome 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....