Gordon Holmes Syndrome (GDHS)

External Ids:

Disease Ontology 12 DOID:0111587 OMIM 56 212840 KEGG 36 H02144 MeSH 43 C565870 D002524 D007006 ICD10 via Orphanet 33 G11.8

UMLS via Orphanet 72 C1859305 Orphanet 58 ORPHA1173 MedGen 41 C1859305 SNOMED-CT via HPO 68 102943000 13649004 15296000 17276009 192073007 237836003 258211005 274524001 278849000 33927004 398151007 398152000 418143002 421689001 4754008 50956007 52073004 52448006 52522001 563001 76976005 8011004 85102008 8619003 95646004 more UMLS 71 C1859305

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. In early adulthood, individuals with Gordon Holmes syndrome develop neurological problems, usually beginning with speech difficulties (dysarthria). As the condition worsens, affected individuals have problems with balance and coordination (cerebellar ataxia), often leading to difficulties with activities of daily living and a need for wheelchair assistance. Some affected individuals also develop memory problems and a decline in intellectual function (dementia).

MalaCards based summary : Gordon Holmes Syndrome, also known as cerebellar ataxia and hypogonadotropic hypogonadism, is related to boucher-neuhauser syndrome and hyperinsulinemic hypoglycemia, familial, 6, and has symptoms including cerebellar ataxia An important gene associated with Gordon Holmes Syndrome is RNF216 (Ring Finger Protein 216), and among its related pathways/superpathways are Innate Immune System and Class I MHC mediated antigen processing and presentation. Affiliated tissues include brain, breast and pituitary, and related phenotypes are neurological speech impairment and optic atrophy

Disease Ontology : ¹² An inherited metabolic disorder characterized by progressive cognitive decline, dementia, hypogonadotropic hypogonadism, and variable movement disorders resulting from disordered ubiquitination that has material basis in homozygous or compound heterozygous mutation in RNF216 on chromosome 7p22.1.

NIH Rare Diseases : ⁵² The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 1173 Definition Cerebellar ataxia -hypogonadism syndrome 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.

OMIM : ⁵⁶ 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)

KEGG : ³⁶ Gordon Holmes syndrome (GHS) is an autosomal recessive adult-onset neurodegenerative disease characterized by cognitive decline, dementia, and other clinical features such as ataxia and hypogonadotropism. Multiple loss-of-function mutations in RNF216 gene have recently been identified in patients suffering from GHS.

UniProtKB/Swiss-Prot : ⁷³ 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.

Clinical features from OMIM:

212840

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Increased viability with MLN4924 (a NAE inhibitor)	GR00250-A-1	9.56	UBE2D2
2	Increased viability with MLN4924 (a NAE inhibitor)	GR00250-A-2	9.56	GLUD1 MAPK1 UBE2D1 UBE2D2 UBE2D4
3	Increased viability with MLN4924 (a NAE inhibitor)	GR00250-A-3	9.56	GLUD1 UBE2L3
4	Synthetic lethal with MLN4924 (a NAE inhibitor)	GR00250-A-1	9.5	GLUD1 RIPK1 UBE2D1 UBE2D3 UBE2D4 UBE2L3
5	Synthetic lethal with MLN4924 (a NAE inhibitor)	GR00250-A-2	9.5	GLUD1 RIPK1 UBE2D1 UBE2D2 UBE2D3 UBE2D4
6	Synthetic lethal with MLN4924 (a NAE inhibitor)	GR00250-A-3	9.5	GLUD1 UBE2L3

Search Clinical Trials , NIH Clinical Center for Gordon Holmes Syndrome

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