Rabson-mendenhall Syndrome malady

NIH Rare Diseases: Rabson-Mendenhall syndrome is a genetic disorder characterized by severe insulin resistance. Insulin, a hormone produced by the pancreas, regulates blood sugar levels by promoting the movement of glucose into cells for energy production or into the liver and fat cells for storage. Symptoms of Rabson-Mendenhall syndrome may include intrauterine and postnatal growth retardation, hypertrophy of muscle and fat tissues, abnormalities of the head and face, abnormalities of the teeth and nails, and skin abnormalities such as acanthosis nigricans. Additional symptoms may also be present. Rabson-Mendenhall syndrome is inherited in an autosomal recessive manner. Treatment is difficult and may include high doses of insulin and/or recombinant insulin-like growth factor.³⁰

MalaCards: Rabson-mendenhall Syndrome, also known as pineal hyperplasia, insulin-resistant diabetes mellitus, and somatic abnormalities, is related to insulin resistance and hepatitis. An important gene associated with Rabson-mendenhall Syndrome is INSR (insulin receptor), and among its related pathways are Aldosterone-regulated sodium reabsorption and Progesterone-mediated oocyte maturation. The compounds ly294002 and c-peptide have been mentioned in the context of this disorder. Affiliated tissues include skin, liver and kidney, and related mouse phenotypes are liver/biliary system and reproductive system.

OMIM: 262190

rabson-mendenhall syndrome 7 30 16 33 32 43 pineal hyperplasia, insulin-resistant diabetes mellitus, and somatic abnormalities 30 16

mendenhall syndrome 30

Diseases related to rabson-mendenhall syndrome by text searches and GeneDecks gene sharing:

(show top 50)    (show all 313)

id	Related Disease	Score	Top Affiliating Genes
1	insulin resistance	30.0	LEP, INS, INSR, IGF1R, IGFBP3, IGF1
2	hepatitis	27.2	LEP, INS, INSR, IGF1R, IGFBP3, IGF1
3	alzheimer disease type 3	13.2	INSR, IGF1
4	insulin autoimmune syndrome	13.1	INS, INSR
5	diffuse idiopathic skeletal hyperostosis	13.1	IGFBP3, IGF1
6	siderosis	13.1	IGFBP3, IGF1
7	ketoacidosis due to scot deficiency	13.1	INS, INSR
8	sheehan syndrome	13.1	INS, IGF1
9	pediatric osteosarcoma	13.1	IGFBP3, IGF1
10	transient neonatal diabetes mellitus	13.1	INS, IGF1
11	diabetic autonomic neuropathy	13.1	INS, IGF1
12	hypothalamic hamartomas	13.0	INS, IGF1
13	empty sella syndrome	13.0	INS, IGFBP3
14	hyperostosis	13.0	IGFBP3, IGF1
15	laron dwarfism	13.0	IGF1, GH1
16	pituitary gland disease	13.0	IGF1, GH1
17	insulin-like growth factor i deficiency	13.0	IGF1, GH1
18	robinow syndrome	13.0	IGF1, GH1
19	mutagen sensitivity	13.0	IGFBP3, IGF1
20	pseudohypoparathyroidism type ia	13.0	IGF1, GH1
21	gonadal disease	13.0	IGF1, GH1
22	lipoatrophic diabetes	13.0	LEP, INS
23	overnutrition	13.0	LEP, INS
24	neonatal diabetes mellitus	13.0	INS, IGF1
25	petrositis	13.0	IGF1, GH1
26	thyrotropin deficiency, isolated	13.0	IGF1, GH1
27	somatotrophinoma	12.9	IGF1, GH1
28	thyroid hormone metabolism	12.9	INS, IGF1
29	congenital generalized lipodystrophy	12.9	LEP, INS
30	alström syndrome	12.9	LEP, INS
31	acute lymphoblastic leukemia, childhood	12.9	LEP, INS
32	hypothyroidism	12.9	LEP, IGFBP3
33	marasmus	12.9	IGFBP3, GH1
34	abetalipoproteinemia	12.9	LEP, IGF1
35	morbid obesity	12.9	LEP, INS
36	familial partial lipodystrophy	12.9	LEP, INS
37	isolated growth hormone deficiency	12.9	IGF1, GH1
38	skin tag	12.9	LEP, INS
39	chronic kidney failure	12.9	LEP, INS
40	prostatic hypertrophy	12.9	IGFBP3, IGF1
41	growth hormone secreting pituitary adenoma	12.9	IGF1, GH1
42	pituitary apoplexy	12.9	INS, GH1
43	aromatase deficiency	12.8	INS, GH1
44	hypoadrenalism	12.8	INS, GH1
45	leptin deficiency	12.8	LEP, GH1
46	panhypopituitarism	12.8	IGF1, GH1
47	hypersomnia	12.8	INS, GH1
48	ring chromosome 15	12.8	IGF1R, IGF1
49	hyperaldosteronism	12.8	INS, INSR
50	pseudohypoparathyroidism	12.8	IGF1, GH1

Clinical features from OMIM: 262190

Approved drugs:

Drug clinical trials:

Genetic tests related to rabson-mendenhall syndrome:

id	Genetic test	Affiliating Genes
1	Rabson-mendenhall Syndrome clinical/research	INSR

MalaCards organs/tissues related to rabson-mendenhall syndrome:

²²

MGI Mouse Phenotypes related to rabson-mendenhall syndrome:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	liver/biliary system phenotype	MP:0005370	9.5	GH1, INS
2	reproductive system phenotype	MP:0005389	9.3	LEP, GH1
3	nervous system phenotype	MP:0003631	9.3	INSR, INS
4	growth/size phenotype	MP:0005378	8.1	GH1, IGF1R, INS, LEP
5	muscle phenotype	MP:0005369	7.8	INSR, LEP, IGFBP3, IGF1, IGF1R
6	cardiovascular system phenotype	MP:0005385	7.8	INS, INSR, IGF1R, IGF1, LEP
7	adipose tissue phenotype	MP:0005375	6.9	GH1, IGF1, IGFBP3, LEP, INS, INSR
8	homeostasis/metabolism phenotype	MP:0005376	6.8	GH1, IGF1, IGFBP3, IGF1R, INSR, INS

Articles related to rabson-mendenhall syndrome:

(show all 14)

id	Title	Authors	Year	Affiliating Genes
1	Rabson-Mendenhall syndrome: two case reports and a br ief review of the literature. (20155514)	Bathi R.J.... Rao R.	2010	INS
2	Two novel mutations in the insulin binding subunit of the insulin receptor gene without insulin binding impairment in a patient with Rabson-Mendenhall syndrome. (18411068)	Thiel C.T.... Rauch A.	2008	INSR, INS
3	Rabson-Mendenhall syndrome: medullary sponge kidney, a new component. (17849153)	Harris A.M.... Kiessling S.G.	2007	INS
4	Functional characterization of a novel insulin receptor mutation contributing to Rabson-Mendenhall syndrome. (17201797)	Tuthill A.... O'Rahilly S.	2007	INSR, INS
5	Efficacy of recombinant methionyl human leptin therapy for the extreme insulin resistance of the Rabson-Mendenhall syndrome. (15070911)	Cochran E.... Gorden P.	2004	INSR, LEP, INS
6	Clinical course of genetic diseases of the insulin receptor (type A and Rabson-Mendenhall syndromes): a 30-year prospective. (15232309)	Musso C.... Gorden P.	2004	INSR, INS
7	Decreased half-life of insulin-like growth factor I in Rabson-Mendenhall syndrome. (11757582)	Longo N.... Elsas L.J.	2001	IGF1, INS
8	Defective insulin receptors in Rabson-Mendenhall syndrome cause complete peripheral insulin resistance but minimal hepatic insulin response remains. (15016231)	Davis A.... Marshall B.A.	2000	INS
9	Progressive decline in insulin levels in Rabson-Mendenhall syndrome. (10443650)	Longo N.... Pasquali M.	1999	INSR, INS
10	Two aberrant splicings caused by mutations in the insulin receptor gene in cultured lymphocytes from a patient with Rabson-Mendenhall's syndrome. (9449692)	Takahashi Y.... Kadowaki T.	1998	INSR, INS
11	Major circadian variations of glucose homeostasis in a patient with Rabson-Mendenhall syndrome and primary insulin resistance due to a mutation (Cys284-->Tyr) in the insulin receptor alpha-subunit. (9212040)	Desbois-Mouthon C.... Capeau J.	1997	INSR, INS
12	Rabson-Mendenhall syndrome (7983791)	Ando A.	1994	IGF1, INS
13	Impaired growth in Rabson-Mendenhall syndrome: lack of effect of growth hormone and insulin-like growth factor-I. (8077364)	Longo N.... Elsas L.J.	1994	IGF1R, IGF1, INS
14	An in-frame insertion in exon 3 and a nonsense mutation in exon 2 of the insulin receptor gene associated with severe insulin resistance in a patient with Rabson-Mendenhall syndrome. (8270132)	Muller-Wieland D.... Maassen J.A.	1993	INSR, INS

Genes related to rabson-mendenhall syndrome according to GeneCards:

id	Symbol	Description	Score	GeneCards Section Context
1	INSR	insulin receptor	11.1	Publications
2	IGFBP3	insulin-like growth factor binding protein 3	11.1
3	IGF1	insulin-like growth factor 1 (somatomedin C)	11.1	Publications
4	INS	insulin	11.1	Publications
5	GH1	growth hormone 1	11.0	Publications
6	IGF1R	insulin-like growth factor 1 receptor	11.0	Publications
7	LEP	leptin	11.0	Publications

Pathways related to rabson-mendenhall syndrome according to GeneDecks:

(show top 50)    (show all 62)

id	Pathway	Score	Top Affiliating Genes
1	Aldosterone-regulated sodium reabsorption20	10.4	INS
2	Progesterone-mediated oocyte maturation20	10.3	INS
3	IRS activation38	10.0	INSR, INS
4	Breast Cancer Regulation by Stathmin136	10.0	IGF1R
5	Akt Signaling36	9.9	IGF1R
6	Ras Pathway36	9.7	IGF1R, INSR
7	Selected targets of GCR-alpha10	9.5	LEP, INS, INSR
8	Adipocytokines & Insulin Signaling37	9.4	LEP, INS, INSR
9	AMPK Enzyme Complex Pathway36	9.3	INS, LEP, INSR
10	MODY (Maturity-Onset Diabetes of Young)36	9.2	INSR, IGF1R, INS
11	Development IGF-RI signaling10	9.2	IGFBP3, IGF1, IGF1R
12	Development_IGF-1 receptor signaling41	9.2	IGFBP3, IGF1R, IGF1
13	Prostate cancer20	9.0	IGF1R, IGF1, INS
14	Oocyte meiosis20	9.0	IGF1R, INS, IGF1
15	Growth Hormone Signaling36	9.0	GH1, IGF1R, IGF1
16	Glucose / Energy Metabolism3	9.0	INS, IGF1R, INSR
17	mTOR Pathway36	8.9	IGF1, INSR, GH1, INS
18	Apoptotic Pathways in Synovial Fibroblasts36	8.8	GH1, IGF1R, IGF1
19	p53 Mediated Apoptosis36	8.8	GH1, IGF1, IGF1R
20	Telomerase Components in Cell Signaling36	8.7	GH1, IGF1R, IGF1
21	Mitochondrial Apoptosis36	8.7	IGF1, GH1, IGF1R
22	DHA Signaling36	8.6	IGF1, GH1, IGF1R
23	Nanog in Mammalian ESC Pluripotency36	8.6	GH1, INSR, IGF1R, IGF1
24	Paxillin Interactions36	8.6	IGF1, GH1, IGF1R, INSR
25	14-3-3 Induced Intracellular Signaling36	8.6	IGF1R, INSR, IGF1, GH1
26	Rap1 Pathway36	8.6	IGF1, GH1, IGF1R, INSR
27	Pancreatic Adenocarcinoma36	8.6	GH1, IGF1, IGF1R, INSR
28	eNOS Signaling36	8.6	INSR, IGF1, IGF1R, GH1
29	NFAT in Immune Response36	8.6	INSR, GH1, IGF1, IGF1R
30	Estrogen Pathway36	8.6	IGF1, IGF1R, INSR, GH1
31	GPCR Pathway36	8.6	GH1, IGF1, IGF1R, INSR
32	GSK3 Signaling36	8.6	INSR, IGF1R, GH1, IGF1
33	ERK5 Signaling36	8.6	IGF1, IGF1R, GH1
34	Nuclear Receptor Activation by Vitamin-A36	8.6	IGF1R, IGF1, GH1
35	JAK-STAT Pathway36	8.6	GH1, IGF1, IGF1R, INSR
36	Tec Kinases Signaling36	8.6	INSR, IGF1R, GH1, IGF1
37	Activation of PKA through GPCR36	8.5	INSR, GH1, IGF1, IGF1R
38	Intracellular Calcium Signaling36	8.5	INSR, IGF1, GH1, IGF1R
39	ILK Signaling36	8.5	IGF1R, INSR, GH1, IGF1
40	p38 Signaling36	8.5	GH1, IGF1, IGF1R, INSR
41	MAPK Signaling36	8.5	GH1, IGF1, IGF1R, INSR
42	Activation of cAMP-Dependent PKA36	8.5	INSR, IGF1R, GH1, IGF1
43	Cellular Apoptosis Pathway36	8.5	IGF1R, IGF1, GH1
44	Rho Family GTPases36	8.5	GH1, IGF1R, IGF1, INSR
45	ERK Signaling36	8.4	IGF1R, IGF1, GH1, INSR
46	Transcription_Receptor-mediated HIF regulation41	8.3	INS, IGF1, IGFBP3, IGF1R, INSR
47	Transcription Receptor-mediated HIF regulation10	8.3	IGF1, IGFBP3, IGF1R, INSR, INS
48	PPAR Pathway36	8.3	GH1, IGF1, IGF1R
49	eIF2 Pathway36	8.1	IGF1, IGF1R, GH1, INSR, INS
50	p70S6K Signaling36	8.1	INSR, IGF1, GH1, IGF1R, INS

Compounds related to rabson-mendenhall syndrome according to GeneDecks:

(show top 50)    (show all 137)

id	Compound	Score	Top Affiliating Genes
1	ly29400232	10.4	LEP
2	c-peptide32	10.0	INSR, LEP
3	progestin32	9.5	INSR, IGF1R
4	2-deoxyglucose32	9.4	INS, INSR, IGF1
5	rapamycin32 42	10.3	IGF1R, INS
6	testosterone32 9 18 9	12.3	INSR, IGF1R, IGFBP3
7	arginine32	9.2	LEP, INS, GH1
8	ghrp32	9.2	IGFBP3, IGF1, GH1
9	pq 40142	9.2	INSR, IGF1R, IGF1
10	demethylasterriquinone b142	9.2	IGF1, INSR, IGF1R
11	megestrol acetate32	9.2	LEP, IGFBP3, IGF1
12	ag 102432	9.1	IGF1R, INSR, IGF1
13	pyridostigmine32 9 9	11.0	IGF1, GH1, IGFBP3
14	pegvisomant32 9 9	11.0	IGFBP3, IGF1, GH1
15	aicar32 42 9 18 9	13.0	LEP, INS, INSR, IGF1
16	epinephrine32 9 18 9	12.0	INS, INSR, IGFBP3, LEP
17	beta-hydroxybutyrate32	8.9	GH1, INS, LEP
18	oxandrolone32 9 9	10.9	IGFBP3, INS, GH1, IGF1
19	hexarelin32	8.9	IGFBP3, GH1, IGF1
20	l-nmma32	8.8	IGF1, INSR, LEP, GH1
21	clonidine32 9 9	10.8	LEP, IGFBP3, IGF1, GH1
22	acipimox32	8.8	INS, LEP, IGF1, GH1
23	cortisone32 18	9.8	IGF1, INS, LEP, GH1
24	triiodothyronine32	8.7	LEP, IGFBP3, GH1, IGF1
25	lanreotide32	8.7	IGFBP3, IGF1, GH1
26	raloxifene32 9 9	10.5	IGFBP3, IGF1, GH1, IGF1R
27	rosiglitazone32 9 18 9	11.4	GH1, IGFBP3, LEP, INS, INSR
28	metformin32 34 9 9	11.4	LEP, GH1, IGF1, INSR, INS
29	glycerol32 9 18 9	11.4	IGFBP3, GH1, INSR, INS, LEP
30	dehydroepiandrosterone sulfate32	8.4	GH1, LEP, INS, IGF1, IGFBP3
31	gnrh32	8.4	INS, LEP, GH1, IGF1, IGFBP3
32	dhea32	8.4	GH1, IGFBP3, INS, LEP, IGF1
33	androstenedione32 18	9.4	LEP, IGF1, GH1, IGFBP3, INS
34	mecasermin32 9 9	10.3	IGF1R, INSR, INS, IGF1, IGFBP3
35	acth32	8.3	GH1, LEP, IGFBP3, IGF1, INS
36	dexamethasone32 42 34 9 9	12.1	INSR, LEP, GH1, IGFBP3, IGF1R
37	creatinine32	8.1	IGF1, GH1, IGFBP3, LEP, IGF1R
38	ibmx32	8.1	IGF1R, INSR, INS, IGF1, GH1
39	vitamin d32	8.1	IGFBP3, INSR, GH1, IGF1, IGF1R
40	thyroxine32 18	9.0	IGF1, LEP, INSR, IGFBP3, GH1, INS
41	tamoxifen32 34 9 9	10.9	IGFBP3, IGF1, GH1, IGF1R, LEP
42	pd 98,05932	7.8	IGF1R, IGF1, GH1, LEP, INSR
43	clomiphene citrate32	7.7	IGF1, IGFBP3, INSR, IGF1R, GH1, INS
44	octreotide32 42 9 9	10.7	IGF1, GH1, INS, INSR, IGF1R, IGFBP3
45	dihydrotestosterone32 9 18 9	10.7	IGF1, GH1, IGFBP3, IGF1R, LEP, INSR
46	cycloheximide32	7.6	IGFBP3, GH1, INSR, IGF1R, LEP, IGF1
47	wortmannin32 42	8.6	IGF1, IGF1R, INSR, INS, LEP, GH1
48	vegf32	7.5	IGFBP3, IGF1, IGF1R, INSR, LEP, GH1
49	estrogen32	7.1	LEP, INS, INSR, IGF1R, IGFBP3, IGF1
50	serine32	7.0	LEP, IGF1, GH1, IGF1R, INSR, INS

Cellular components related to rabson-mendenhall syndrome according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	insulin-like growth factor binding protein complex	GO:016942	9.5	IGF1, IGFBP3
2	extracellular region	GO:005576	7.9	GH1, IGF1, IGFBP3, INS, LEP
3	extracellular space	GO:005615	7.6	GH1, IGF1, IGFBP3, INS, LEP

Biological processes related to rabson-mendenhall syndrome according to GeneDecks:

(show all 25)

id	Name	GO ID	Score	Top Affiliating Genes
1	positive regulation of developmental growth	GO:048639	9.9	LEP, INSR
2	positive regulation of respiratory burst	GO:060267	9.9	INS, INSR
3	exocrine pancreas development	GO:031017	9.9	INSR, IGF1
4	bone mineralization involved in bone maturation	GO:035630	9.8	LEP, IGF1
5	activation of protein kinase B activity	GO:032148	9.8	INS, INSR
6	positive regulation of insulin receptor signaling pathway	GO:046628	9.7	INS, LEP
7	positive regulation of nitric oxide biosynthetic process	GO:045429	9.5	INSR, INS
8	positive regulation of glycolysis	GO:045821	9.5	INSR, IGF1, INS
9	positive regulation of glycogen biosynthetic process	GO:045725	9.5	IGF1, INS, INSR
10	positive regulation of tyrosine phosphorylation of Stat5 protein	GO:042523	9.5	IGF1, GH1
11	positive regulation of glucose import	GO:046326	9.5	INS, IGF1, INSR
12	positive regulation of mitosis	GO:045840	9.4	INS, INSR, IGF1
13	positive regulation of protein kinase B signaling cascade	GO:051897	9.4	IGF1, INSR, INS
14	negative regulation of protein phosphorylation	GO:001933	9.4	INSR, IGFBP3
15	positive regulation of insulin-like growth factor receptor signaling pathway	GO:043568	9.3	IGF1, IGFBP3, GH1
16	positive regulation of tyrosine phosphorylation of Stat3 protein	GO:042517	9.3	LEP, GH1
17	insulin-like growth factor receptor signaling pathway	GO:048009	9.3	IGF1, IGF1R
18	positive regulation of phosphatidylinositol 3-kinase cascade	GO:014068	9.2	GH1, IGF1, INS
19	positive regulation of peptidyl-tyrosine phosphorylation	GO:050731	9.1	INS, IGF1, GH1
20	positive regulation of cell migration	GO:030335	9.0	INSR, INS, IGF1R
21	insulin receptor signaling pathway	GO:008286	8.9	INSR, IGF1R, INS
22	positive regulation of DNA replication	GO:045740	8.7	INS, INSR, IGF1R, IGF1
23	negative regulation of apoptotic process	GO:043066	8.6	IGF1R, INS, LEP
24	positive regulation of MAPK cascade	GO:043410	8.6	LEP, IGF1, INS, IGFBP3, INSR
25	positive regulation of cell proliferation	GO:008284	8.1	IGF1, IGF1R, INSR, INS, LEP

Molecular functions related to rabson-mendenhall syndrome according to GeneDecks:

(show all 10)

id	Name	GO ID	Score	Top Affiliating Genes
1	insulin-like growth factor II binding	GO:031995	9.8	IGFBP3, INSR
2	insulin binding	GO:043559	9.3	IGF1R, INSR
3	insulin-like growth factor receptor binding	GO:005159	9.3	IGF1, INSR, INS
4	insulin receptor substrate binding	GO:043560	9.3	INSR, IGF1R
5	insulin-like growth factor binding	GO:005520	9.2	IGFBP3, IGF1R
6	phosphatidylinositol 3-kinase binding	GO:043548	9.2	INSR, IGF1R
7	insulin-like growth factor I binding	GO:031994	9.1	IGFBP3, IGF1R, INSR
8	insulin receptor binding	GO:005158	8.8	IGF1R, IGF1, INS
9	growth factor activity	GO:008083	8.6	GH1, LEP, IGF1
10	hormone activity	GO:005179	8.6	GH1, IGF1, INS, LEP