MCID: GRD009
MIFTS: 38

Gordon Holmes Syndrome

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Reproductive diseases, Endocrine diseases

Aliases & Classifications for Gordon Holmes Syndrome

MalaCards integrated aliases for Gordon Holmes Syndrome:

Name: Gordon Holmes Syndrome 57 25 75 29 6
Cerebellar Ataxia and Hypogonadotropic Hypogonadism 57 53 25 75 73
Lhrh Deficiency and Ataxia 57 53 25 75
Deficiency of Luteinizing Hormone-Releasing Hormone with Ataxia 25 75
Luteinizing Hormone-Releasing Hormone Deficiency with Ataxia 53 59
Cerebellar Ataxia-Hypogonadism Syndrome 53 59
Gordon-Holmes Syndrome 53 59
Gdhs 57 75
Cahh 57 75
Luteinizing Hormone-Releasing Hormone, Deficiency of, with Ataxia 57
Luteinizing Hormone Releasing Hormone, Deficiency of with Ataxia 53
Cerebellar Ataxia and Hypogonadotropic Hypogonadism; Cahh 57
Ataxia, Cerebellar, and Hypogonadotropic Hypogonadism 40
Cerebellar Ataxia - Hypogonadism 53

Characteristics:

Orphanet epidemiological data:

59
cerebellar ataxia-hypogonadism syndrome
Inheritance: Autosomal recessive; Age of onset: All ages;

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
gordon holmes syndrome:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Gordon Holmes Syndrome

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1173Disease definitionCerebellar ataxia-hypogonadismsyndrome is a very rare autosomal recessive neurodegenerative disorder characterized by the combination of progressive cerebellar ataxia with onset from early childhood to the fourth decade, and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics). Cerebellar ataxia-hypogonadism syndrome belongs to a clinical continuum of neurodegenerative disorders along with clinically overlapping disorders such as ataxia-hypogonadism-choroidal dystrophy syndrome (see this term).Visit the Orphanet disease page for more resources.

MalaCards based summary : Gordon Holmes Syndrome, also known as cerebellar ataxia and hypogonadotropic hypogonadism, is related to hyperinsulinemic hypoglycemia, familial, 6 and boucher-neuhauser syndrome, and has symptoms including cerebellar ataxia An important gene associated with Gordon Holmes Syndrome is RNF216 (Ring Finger Protein 216). Affiliated tissues include brain, breast and pituitary, and related phenotypes are nystagmus and ataxia

OMIM : 57 Gordon Holmes syndrome is an autosomal recessive adult-onset neurodegenerative disorder characterized by progressive cognitive decline, dementia, and variable movement disorders, such as ataxia and chorea. The neurologic phenotype is associated with hypogonadotropic hypogonadism (summary by Santens et al., 2015). (212840)

UniProtKB/Swiss-Prot : 75 Gordon Holmes syndrome: A disease characterized by cerebellar symptoms and signs of sex steroid deficiency. Clinical features include cerebellar and brain stem atrophy, cerebellar ataxia, hypothalamic LHRH deficiency, hypogonadotrophic hypogonadism, lack of secondary sexual characteristics, and infertility.

Genetics Home Reference : 25 Gordon Holmes syndrome is a rare condition characterized by reproductive and neurological problems. One of the key features of the condition is reduced production of hormones that direct sexual development (hypogonadotropic hypogonadism). Many affected individuals have a delay in development of the typical signs of puberty, such as the growth of facial hair and deepening of the voice in males, and the start of monthly periods (menstruation) and breast development in females. Some never undergo puberty. While some people with Gordon Holmes syndrome seem to have normal puberty, they develop other problems with the reproductive system later in life.

Related Diseases for Gordon Holmes Syndrome

Diseases related to Gordon Holmes Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hyperinsulinemic hypoglycemia, familial, 6 11.2
2 boucher-neuhauser syndrome 11.2
3 ataxia - hypogonadism - choroidal dystrophy 10.9
4 neuropathy 10.0
5 aceruloplasminemia 9.8
6 ataxia-oculomotor apraxia 3 9.8
7 hypogonadism 9.8

Graphical network of the top 20 diseases related to Gordon Holmes Syndrome:



Diseases related to Gordon Holmes Syndrome

Symptoms & Phenotypes for Gordon Holmes Syndrome

Symptoms via clinical synopsis from OMIM:

57
Voice:
dysarthria

Neurologic Central Nervous System:
dementia
cerebellar atrophy
cerebral atrophy
cerebellar ataxia
chorea, prominent (in some patients)

Genitourinary Internal Genitalia Female:
amenorrhea, primary or secondary (in some patients)
oligomenorrhea (in some patients)

Endocrine Features:
hypogonadotrophic hypogonadism
secondary sexual characteristics lacking
hypothalamic and/or pituitary defect
gonadotropin response to exogenous luteinizing hormone releasing hormone (lhrh, in some patients)

GenitourinaryInternal GenitaliaMale:
no spontaneous puberty (in some patients)
small, soft testes (in some patients)


Clinical features from OMIM:

212840

Human phenotypes related to Gordon Holmes Syndrome:

59 32 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 59 32 hallmark (90%) Very frequent (99-80%) HP:0000639
2 ataxia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001251
3 muscular hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001252
4 neurological speech impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0002167
5 optic atrophy 59 32 hallmark (90%) Very frequent (99-80%) HP:0000648
6 short stature 59 32 occasional (7.5%) Occasional (29-5%) HP:0004322
7 abnormality of retinal pigmentation 59 32 hallmark (90%) Very frequent (99-80%) HP:0007703
8 brachycephaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0000248
9 hemiplegia/hemiparesis 59 32 frequent (33%) Frequent (79-30%) HP:0004374
10 abnormal electroretinogram 59 32 hallmark (90%) Very frequent (99-80%) HP:0000512
11 hypogonadotrophic hypogonadism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000044
12 clinodactyly of the 5th finger 59 32 occasional (7.5%) Occasional (29-5%) HP:0004209
13 dementia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000726
14 decreased fertility 59 32 hallmark (90%) Very frequent (99-80%) HP:0000144
15 gynecomastia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000771
16 supernumerary nipple 59 32 occasional (7.5%) Occasional (29-5%) HP:0002558
17 abnormality of the hypothalamus-pituitary axis 59 32 hallmark (90%) Very frequent (99-80%) HP:0000864
18 personality changes 59 32 occasional (7.5%) Occasional (29-5%) HP:0000751
19 dysarthria 32 HP:0001260
20 behavioral abnormality 59 Occasional (29-5%)
21 abnormality of metabolism/homeostasis 32 HP:0001939
22 abnormality of the skeletal system 32 HP:0000924
23 hypogonadism 59 Very frequent (99-80%)
24 infertility 32 HP:0000789
25 cerebellar atrophy 32 HP:0001272
26 cerebral atrophy 32 HP:0002059
27 oligomenorrhea 32 occasional (7.5%) HP:0000876
28 chorioretinal dystrophy 32 HP:0001135

UMLS symptoms related to Gordon Holmes Syndrome:


cerebellar ataxia

Drugs & Therapeutics for Gordon Holmes Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Gordon Holmes Syndrome

Genetic Tests for Gordon Holmes Syndrome

Genetic tests related to Gordon Holmes Syndrome:

# Genetic test Affiliating Genes
1 Gordon Holmes Syndrome 29 RNF216

Anatomical Context for Gordon Holmes Syndrome

MalaCards organs/tissues related to Gordon Holmes Syndrome:

41
Brain, Breast, Pituitary, Testes, Hypothalamus

Publications for Gordon Holmes Syndrome

Articles related to Gordon Holmes Syndrome:

# Title Authors Year
1
Rare case of Gordon Holmes syndrome. ( 29954774 )
2018
2
TRIAD3/RNF216 mutations associated with Gordon Holmes syndrome lead to synaptic and cognitive impairments via Arc misregulation. ( 27995769 )
2017
3
Gordon Holmes syndrome: finally genotype meets phenotype. ( 28972031 )
2017
4
STUB1/CHIP mutations cause Gordon Holmes syndrome as part of a widespread multisystemic neurodegeneration: evidence from four novel mutations. ( 28193273 )
2017
5
PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum. ( 24355708 )
2014
6
Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in Gordon Holmes syndrome. ( 25033069 )
2014
7
Familial cerebellar ataxia and hypogonadotropic hypogonadism: evidence for hypothalamic LHRH deficiency. ( 6813427 )
1982
8
Autosomal recessive syndrome of cerebellar ataxia and hypogonadotropic hypogonadism. ( 1149314 )
1975

Variations for Gordon Holmes Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Gordon Holmes Syndrome:

75
# Symbol AA change Variation ID SNP ID
1 RNF216 p.Arg660Cys VAR_070048
2 RNF216 p.Arg694Cys VAR_070049 rs387907368

ClinVar genetic disease variations for Gordon Holmes Syndrome:

6
(show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 RNF216 NM_207111.3(RNF216): c.2251C> T (p.Arg751Cys) single nucleotide variant Pathogenic rs387907368 GRCh37 Chromosome 7, 5680916: 5680916
2 RNF216 NM_207111.3(RNF216): c.2251C> T (p.Arg751Cys) single nucleotide variant Pathogenic rs387907368 GRCh38 Chromosome 7, 5641285: 5641285
3 RNF216 NM_207111.3(RNF216): c.1791T> A (p.Cys597Ter) single nucleotide variant Pathogenic rs387907369 GRCh37 Chromosome 7, 5754726: 5754726
4 RNF216 NM_207111.3(RNF216): c.1791T> A (p.Cys597Ter) single nucleotide variant Pathogenic rs387907369 GRCh38 Chromosome 7, 5715095: 5715095
5 RNF216 NM_207111.3(RNF216): c.615_616delGA (p.Glu205Aspfs) deletion Pathogenic rs387907370 GRCh37 Chromosome 7, 5781032: 5781033
6 RNF216 NM_207111.3(RNF216): c.615_616delGA (p.Glu205Aspfs) deletion Pathogenic rs387907370 GRCh38 Chromosome 7, 5741401: 5741402
7 RNF216 NM_207111.3(RNF216): c.1367G> A (p.Gly456Glu) single nucleotide variant Pathogenic rs794728000 GRCh37 Chromosome 7, 5769085: 5769085
8 RNF216 NM_207111.3(RNF216): c.1367G> A (p.Gly456Glu) single nucleotide variant Pathogenic rs794728000 GRCh38 Chromosome 7, 5729454: 5729454
9 RNF216 NM_207111.3(RNF216): c.904C> T (p.Gln302Ter) single nucleotide variant Pathogenic rs373785974 GRCh37 Chromosome 7, 5780744: 5780744
10 RNF216 NM_207111.3(RNF216): c.904C> T (p.Gln302Ter) single nucleotide variant Pathogenic rs373785974 GRCh38 Chromosome 7, 5741113: 5741113
11 RNF216 NM_207111.3(RNF216): c.1616A> G (p.Tyr539Cys) single nucleotide variant Pathogenic rs148642312 GRCh37 Chromosome 7, 5760692: 5760692
12 RNF216 NM_207111.3(RNF216): c.1616A> G (p.Tyr539Cys) single nucleotide variant Pathogenic rs148642312 GRCh38 Chromosome 7, 5721061: 5721061

Expression for Gordon Holmes Syndrome

Search GEO for disease gene expression data for Gordon Holmes Syndrome.

Pathways for Gordon Holmes Syndrome

GO Terms for Gordon Holmes Syndrome

Cellular components related to Gordon Holmes Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane raft GO:0045121 8.96 ARC RIPK1
2 ubiquitin ligase complex GO:0000151 8.62 RNF216 STUB1

Biological processes related to Gordon Holmes Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043161 8.96 RNF216 STUB1
2 protein homooligomerization GO:0051260 8.62 ARC RIPK1

Molecular functions related to Gordon Holmes Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ubiquitin protein ligase activity GO:0061630 8.62 RNF216 STUB1

Sources for Gordon Holmes Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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