MCID: CRB055
MIFTS: 32

Cerebellar Ataxia and Hypogonadotropic Hypogonadism

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

Aliases & Classifications for Cerebellar Ataxia and Hypogonadotropic Hypogonadism

MalaCards integrated aliases for Cerebellar Ataxia and Hypogonadotropic Hypogonadism:

Name: Cerebellar Ataxia and Hypogonadotropic Hypogonadism 54 50 24 25 71 69
Gordon Holmes Syndrome 24 25 71 29
Lhrh Deficiency and Ataxia 50 25 71
Deficiency of Luteinizing Hormone-Releasing Hormone with Ataxia 25 71
Luteinizing Hormone-Releasing Hormone Deficiency with Ataxia 50 56
Cerebellar Ataxia-Hypogonadism Syndrome 50 56
Gordon-Holmes Syndrome 50 56
Gdhs 24 71
Luteinizing Hormone Releasing Hormone, Deficiency of with Ataxia 50
Cerebellar Ataxia - Hypogonadism 50
Cahh 71

Characteristics:

Orphanet epidemiological data:

56
cerebellar ataxia-hypogonadism syndrome
Inheritance: Autosomal recessive; Age of onset: All ages;

OMIM:

54
Inheritance:
autosomal recessive


HPO:

32
cerebellar ataxia and hypogonadotropic hypogonadism:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Cerebellar Ataxia and Hypogonadotropic Hypogonadism

NIH Rare Diseases : 50 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. last updated: 11/30/2014

MalaCards based summary : Cerebellar Ataxia and Hypogonadotropic Hypogonadism, also known as gordon holmes syndrome, is related to hyperinsulinism-hyperammonemia syndrome and boucher-neuhauser syndrome, and has symptoms including short stature, optic atrophy and nystagmus. An important gene associated with Cerebellar Ataxia and Hypogonadotropic Hypogonadism is RNF216 (Ring Finger Protein 216). Affiliated tissues include brain, pituitary and testes.

UniProtKB/Swiss-Prot : 71 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.

OMIM : 54
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)

Related Diseases for Cerebellar Ataxia and Hypogonadotropic Hypogonadism

Diseases related to Cerebellar Ataxia and Hypogonadotropic Hypogonadism via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 hyperinsulinism-hyperammonemia syndrome 11.2
2 boucher-neuhauser syndrome 11.1
3 ataxia - hypogonadism - choroidal dystrophy 10.8
4 ataxia 10.2
5 cerebellar ataxia 10.2
6 hypogonadotropic hypogonadism 10.2
7 hypogonadism 10.2
8 hypogonadotropism 10.2
9 hand-foot-uterus syndrome 9.5 PNPLA6 RNF216

Graphical network of the top 20 diseases related to Cerebellar Ataxia and Hypogonadotropic Hypogonadism:



Diseases related to Cerebellar Ataxia and Hypogonadotropic Hypogonadism

Symptoms & Phenotypes for Cerebellar Ataxia and Hypogonadotropic Hypogonadism

Symptoms via clinical synopsis from OMIM:

54

Voice:
dysarthria

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

Genitourinary- Internal Genitalia Male:
no spontaneous puberty (in some patients)
small, soft testes (in some patients)

Neurologic- Central Nervous System:
cerebral atrophy
cerebellar ataxia
cerebellar atrophy
dementia
chorea, prominent (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)


Clinical features from OMIM:

212840

Human phenotypes related to Cerebellar Ataxia and Hypogonadotropic Hypogonadism:

56 32 (show all 28)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short stature 56 32 occasional (7.5%) Occasional (29-5%) HP:0004322
2 optic atrophy 56 32 hallmark (90%) Very frequent (99-80%) HP:0000648
3 nystagmus 56 32 hallmark (90%) Very frequent (99-80%) HP:0000639
4 ataxia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001251
5 personality changes 56 32 occasional (7.5%) Occasional (29-5%) HP:0000751
6 brachycephaly 56 32 occasional (7.5%) Occasional (29-5%) HP:0000248
7 dementia 56 32 occasional (7.5%) Occasional (29-5%) HP:0000726
8 muscular hypotonia 56 32 frequent (33%) Frequent (79-30%) HP:0001252
9 gynecomastia 56 32 hallmark (90%) Very frequent (99-80%) HP:0000771
10 decreased fertility 56 32 hallmark (90%) Very frequent (99-80%) HP:0000144
11 abnormal electroretinogram 56 32 hallmark (90%) Very frequent (99-80%) HP:0000512
12 hypogonadotrophic hypogonadism 56 32 hallmark (90%) Very frequent (99-80%) HP:0000044
13 supernumerary nipple 56 32 occasional (7.5%) Occasional (29-5%) HP:0002558
14 neurological speech impairment 56 32 hallmark (90%) Very frequent (99-80%) HP:0002167
15 abnormality of retinal pigmentation 56 32 hallmark (90%) Very frequent (99-80%) HP:0007703
16 hemiplegia/hemiparesis 56 32 frequent (33%) Frequent (79-30%) HP:0004374
17 clinodactyly of the 5th finger 56 32 occasional (7.5%) Occasional (29-5%) HP:0004209
18 abnormality of the hypothalamus-pituitary axis 56 32 hallmark (90%) Very frequent (99-80%) HP:0000864
19 dysarthria 32 HP:0001260
20 cerebral atrophy 32 HP:0002059
21 infertility 32 HP:0000789
22 cerebellar atrophy 32 HP:0001272
23 hypogonadism 56 Very frequent (99-80%)
24 oligomenorrhea 32 occasional (7.5%) HP:0000876
25 chorioretinal dystrophy 32 HP:0001135
26 behavioral abnormality 56 Occasional (29-5%)
27 abnormality of metabolism/homeostasis 32 HP:0001939
28 abnormality of the skeletal system 32 HP:0000924

UMLS symptoms related to Cerebellar Ataxia and Hypogonadotropic Hypogonadism:


cerebellar ataxia

Drugs & Therapeutics for Cerebellar Ataxia and Hypogonadotropic Hypogonadism

Interventional clinical trials:


id 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 Cerebellar Ataxia and Hypogonadotropic Hypogonadism

Genetic Tests for Cerebellar Ataxia and Hypogonadotropic Hypogonadism

Genetic tests related to Cerebellar Ataxia and Hypogonadotropic Hypogonadism:

id Genetic test Affiliating Genes
1 Gordon Holmes Syndrome 29 24 RNF216

Anatomical Context for Cerebellar Ataxia and Hypogonadotropic Hypogonadism

MalaCards organs/tissues related to Cerebellar Ataxia and Hypogonadotropic Hypogonadism:

39
Brain, Pituitary, Testes, Hypothalamus

Publications for Cerebellar Ataxia and Hypogonadotropic Hypogonadism

Articles related to Cerebellar Ataxia and Hypogonadotropic Hypogonadism:

id Title Authors Year
1
Familial cerebellar ataxia and hypogonadotropic hypogonadism: evidence for hypothalamic LHRH deficiency. ( 6813427 )
1982
2
Autosomal recessive syndrome of cerebellar ataxia and hypogonadotropic hypogonadism. ( 1149314 )
1975

Variations for Cerebellar Ataxia and Hypogonadotropic Hypogonadism

UniProtKB/Swiss-Prot genetic disease variations for Cerebellar Ataxia and Hypogonadotropic Hypogonadism:

71
id 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 Cerebellar Ataxia and Hypogonadotropic Hypogonadism:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 RNF216 NM_207111.3(RNF216): c.2251C> T (p.Arg751Cys) single nucleotide variant Pathogenic rs387907368 GRCh38 Chromosome 7, 5641285: 5641285
2 RNF216 NM_207111.3(RNF216): c.1791T> A (p.Cys597Ter) single nucleotide variant Pathogenic rs387907369 GRCh37 Chromosome 7, 5754726: 5754726
3 RNF216 NM_207111.3(RNF216): c.615_616delGA (p.Glu205Aspfs) deletion Pathogenic rs387907370 GRCh37 Chromosome 7, 5781032: 5781033
4 RNF216 NM_207111.3(RNF216): c.1367G> A (p.Gly456Glu) single nucleotide variant Pathogenic rs794728000 GRCh37 Chromosome 7, 5769085: 5769085
5 RNF216 NM_207111.3(RNF216): c.904C> T (p.Gln302Ter) single nucleotide variant Pathogenic rs373785974 GRCh37 Chromosome 7, 5780744: 5780744
6 RNF216 NM_207111.3(RNF216): c.1616A> G (p.Tyr539Cys) single nucleotide variant Pathogenic rs148642312 GRCh37 Chromosome 7, 5760692: 5760692

Expression for Cerebellar Ataxia and Hypogonadotropic Hypogonadism

Search GEO for disease gene expression data for Cerebellar Ataxia and Hypogonadotropic Hypogonadism.

Pathways for Cerebellar Ataxia and Hypogonadotropic Hypogonadism

GO Terms for Cerebellar Ataxia and Hypogonadotropic Hypogonadism

Sources for Cerebellar Ataxia and Hypogonadotropic Hypogonadism

3 CDC
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11 DGIdb
16 ExPASy
18 FMA
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30 HGMD
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42 MeSH
43 MESH via Orphanet
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59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
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70 UMLS via Orphanet
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