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 56 12 73
Deafness Enamel Hypoplasia Nail Defects 52 73 29 6 71
Sensorineural Hearing Loss, Enamel Hypoplasia, and Nail Abnormalities 52 73
Hearing Loss, Sensorineural, with Enamel Hypoplasia and Nail Defects 56 73
Deafness-Enamel Hypoplasia-Nail Defects Syndrome 12 58
Peroxisome Biogenesis Disorder 1c 56 73
Heimler Syndrome 52 58
Hmlr1 56 73
Pbd1c 56 73
Bilateral Sensorineural Hearing Loss, Enamel Hypoplasia and Nail Defects 52
Hearing Loss-Enamel Hypoplasia-Nail Defects Syndrome 58
Peroxisome Biogenesis Disorder 1c; Pbd1c 56
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:

56
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

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 3220 Definition Deafness-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 zellweger spectrum disorder. An important gene associated with Heimler Syndrome 1 is PEX1 (Peroxisomal Biogenesis Factor 1), and among its related pathways/superpathways is Peroxisome. Affiliated tissues include skin, and related phenotypes are intellectual disability and sensorineural hearing impairment

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 : 56 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)

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 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 sensorineural hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000407
3 diabetes mellitus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000819
4 taurodontia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000679
5 abnormality of dental enamel 58 31 hallmark (90%) Very frequent (99-80%) HP:0000682
6 abnormal hair quantity 58 31 hallmark (90%) Very frequent (99-80%) HP:0011362
7 abnormal toenail morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0008388
8 hypogonadism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000135
9 abnormality of nail color 58 31 hallmark (90%) Very frequent (99-80%) HP:0100643
10 pili torti 58 31 hallmark (90%) Very frequent (99-80%) HP:0003777
11 external genital hypoplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0003241
12 thin eyebrow 58 31 hallmark (90%) Very frequent (99-80%) HP:0045074
13 abnormal nasolacrimal system morphology 31 hallmark (90%) HP:0000614
14 abnormal eyelid morphology 31 hallmark (90%) HP:0000492
15 abnormal fingernail morphology 31 hallmark (90%) HP:0001231
16 short stature 58 31 frequent (33%) Frequent (79-30%) HP:0004322
17 arrhythmia 58 31 frequent (33%) Frequent (79-30%) HP:0011675
18 primary amenorrhea 58 31 frequent (33%) Frequent (79-30%) HP:0000786
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 delayed skeletal maturation 58 31 occasional (7.5%) Occasional (29-5%) HP:0002750
22 ichthyosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0008064
23 sensory neuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000763
24 high anterior hairline 58 31 occasional (7.5%) Occasional (29-5%) HP:0009890
25 hyporeflexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001265
26 cerebral calcification 58 31 occasional (7.5%) Occasional (29-5%) HP:0002514
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 peripheral neuropathy 58 Occasional (29-5%)
34 abnormality of the fingernails 58 Very frequent (99-80%)
35 abnormality of the eyelid 58 Very frequent (99-80%)
36 abnormality of the eyebrow 58 Very frequent (99-80%)
37 abnormality of the nasolacrimal system 58 Very frequent (99-80%)
38 amelogenesis imperfecta 31 HP:0000705
39 hypoplasia of dental enamel 31 HP:0006297
40 leukonychia 31 HP:0001820

Symptoms via clinical synopsis from OMIM:

56
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

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

MalaCards organs/tissues related to Heimler Syndrome 1:

40
Skin

Publications for Heimler Syndrome 1

Articles related to Heimler Syndrome 1:

(show all 12)
# Title Authors PMID Year
1
Sensorineural hearing loss, enamel hypoplasia, and nail abnormalities in sibs. 61 6 56
2063923 1991
2
Heimler Syndrome Is Caused by Hypomorphic Mutations in the Peroxisome-Biogenesis Genes PEX1 and PEX6. 56 6
26387595 2015
3
Spectrum of PEX6 mutations in Zellweger syndrome spectrum patients. 6
19877282 2010
4
Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders. 6
19105186 2009
5
Peroxisome biogenesis disorders. 6
17055079 2006
6
Sensorineural deafness, enamel abnormalities and nail abnormalities: a case report of Heimler syndrome in identical twin girls. 6
16530715 2006
7
The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum. 6
15542397 2004
8
Sensorineural hearing loss and enamel hypoplasia with subtle nail findings: another family with Heimler's syndrome. 56
12514367 2003
9
Amelogenesis imperfecta, sensorineural hearing loss, and Beau's lines, a second case report of Heimler's syndrome. 56
10636745 1999
10
Identification of a common PEX1 mutation in Zellweger syndrome. 6
10447258 1999
11
Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders. 6
9398847 1997
12
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 19) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PEX1 NM_000466.3(PEX1):c.2528G>A (p.Gly843Asp)SNV Pathogenic 7516 rs61750420 7:92130876-92130876 7:92501562-92501562
2 PEX1 NM_000466.3(PEX1):c.2097dup (p.Ile700fs)duplication Pathogenic 7519 rs61750415 7:92132483-92132484 7:92503169-92503170
3 PEX1 NM_000466.3(PEX1):c.1742G>C (p.Arg581Pro)SNV Pathogenic 217429 rs370483961 7:92136369-92136369 7:92507055-92507055
4 PEX1 NM_000466.3(PEX1):c.1239+1G>TSNV Pathogenic 217430 rs756876301 7:92146589-92146589 7:92517275-92517275
5 PEX1 NM_000466.3(PEX1):c.3750G>A (p.Trp1250Ter)SNV Pathogenic 217431 rs863225085 7:92118624-92118624 7:92489310-92489310
6 PEX1 NM_000466.3(PEX1):c.3379dup (p.Arg1127fs)duplication Pathogenic 203390 rs794729652 7:92120644-92120645 7:92491330-92491331
7 PEX1 NM_000466.3(PEX1):c.1792del (p.Thr598fs)deletion Pathogenic 224324 rs886037783 7:92136319-92136319 7:92507005-92507005
8 PEX1 NM_000466.3(PEX1):c.2922del (p.Leu974fs)deletion Pathogenic 371696 rs762324548 7:92123805-92123805 7:92494491-92494491
9 PEX1 NM_000466.3(PEX1):c.2992C>T (p.Arg998Ter)SNV Pathogenic/Likely pathogenic 495880 rs61750428 7:92123645-92123645 7:92494331-92494331
10 PEX1 NM_000466.3(PEX1):c.1991T>C (p.Leu664Pro)SNV Likely pathogenic 7517 rs121434455 7:92134126-92134126 7:92504812-92504812
11 PEX1 NM_000466.3(PEX1):c.2114T>G (p.Leu705Trp)SNV Conflicting interpretations of pathogenicity 217428 rs863225084 7:92132467-92132467 7:92503153-92503153
12 PEX1 NM_000466.3(PEX1):c.2966T>C (p.Ile989Thr)SNV Conflicting interpretations of pathogenicity 224325 rs61750427 7:92123671-92123671 7:92494357-92494357
13 PEX1 NM_000466.3(PEX1):c.3503A>G (p.Asp1168Gly)SNV Uncertain significance 282718 rs182452430 7:92119161-92119161 7:92489847-92489847
14 PEX1 NM_000466.3(PEX1):c.2750C>T (p.Ala917Val)SNV Uncertain significance 288721 rs371327573 7:92126060-92126060 7:92496746-92496746
15 PEX1 NM_000466.3(PEX1):c.665C>T (p.Thr222Ile)SNV Uncertain significance 197673 rs773922257 7:92147164-92147164 7:92517850-92517850
16 PEX1 NM_000466.3(PEX1):c.1249G>A (p.Asp417Asn)SNV Uncertain significance 498412 rs143273433 7:92143272-92143272 7:92513958-92513958
17 PEX1 NM_000466.3(PEX1):c.254G>A (p.Gly85Glu)SNV Uncertain significance 502318 rs771224088 7:92151435-92151435 7:92522121-92522121
18 PEX1 NM_000466.3(PEX1):c.3756T>A (p.Asn1252Lys)SNV Uncertain significance 548004 rs553001596 7:92118618-92118618 7:92489304-92489304
19 PEX1 NM_000466.3(PEX1):c.2876G>C (p.Arg959Pro)SNV Uncertain significance 587523 rs773206107 7:92123851-92123851 7:92494537-92494537

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 9.26 PEX6 PEX1
2 ATPase activity GO:0016887 9.16 PEX6 PEX1
3 protein C-terminus binding GO:0008022 8.96 PEX6 PEX1
4 ATPase activity, coupled GO:0042623 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
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....