MCID: GRW003
MIFTS: 20

Growth Hormone Insensitivity with Immunodeficiency

Categories: Genetic diseases, Rare diseases, Endocrine diseases, Blood diseases, Immune diseases

Aliases & Classifications for Growth Hormone Insensitivity with Immunodeficiency

MalaCards integrated aliases for Growth Hormone Insensitivity with Immunodeficiency:

Name: Growth Hormone Insensitivity with Immunodeficiency 57 53 75 37 29 13 6 40
Growth Hormone Insensitivity Due to Postreceptor Defect 57 53 75
Laron Syndrome Due to Postreceptor Defect 57 53
Laron Syndrome Due to a Post-Receptor Defect 75
Short Stature Due to Stat5b Deficiency 59
Laron Syndrome with Immunodeficiency 59
Laron Syndrome Type Ii 75
Laron Type Dwarfism Ii 75
Laron-Like Syndrome 59
Ghii 75

Characteristics:

Orphanet epidemiological data:

59
laron syndrome with immunodeficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

Classifications:



External Ids:

OMIM 57 245590
Orphanet 59 ORPHA220465
ICD10 via Orphanet 34 D82.8 E34.3
MedGen 42 C1855548
MeSH 44 D046150
KEGG 37 H00931

Summaries for Growth Hormone Insensitivity with Immunodeficiency

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 181393Disease definitionGrowth hormone insensitivity syndrome (GHIS) is a group of diseases characterized by marked short stature associated with normal or elevated growth hormone (GH) concentrations, which fail to respond to exogenous GH administration. GHIS comprises growth delay due to IGF-1 deficiency, growth delay due to IGF-1 resistance, Laron syndrome, short stature due to STAT5b deficiency and primary acid-labile subunit (ALS) deficiency (see these terms).EpidemiologyA few cases of IGF-1 deficiency, IGF-1 resistance, STAT5B and ALS deficiencies, and more than 250 cases of Laron syndrome have been reported in the literature so far. Males and females are equally affected.Clinical descriptionIntrauterine growth and birth size are usually subnormal. Postnatal growth is slowed. Facial dysmorphism is common and includes microcephaly, thin upper and everted lower lips and small chin. Disproportional growth, delayed motor development and delayed puberty have been described in some cases and relative obesity may occur in young adults. Intellectual development varies from normal intelligence to intellectual deficiency. Despite sharing short stature and the classical biochemical features of GH insensitivity, affected individuals present heterogeneous clinical features depending on the genetic condition. Immune deficiency has been described in some cases of STAT5b deficiency. Hearing loss has been described in some cases of IGF-1 deficiency.EtiologyGHIS is due to mutations in the growth hormone receptor (GHR) gene (Laron syndrome) or to post receptor defects due to mutations in the IGF-1 (IGF-1 deficiency and IGF-1 resistance), IGFALS (short stature due to primary ALS deficiency) or STAT5B genes (STAT5b deficiency). Transmission is autosomal recessive.Diagnostic methodsThe diagnosis is based on clinical and biological findings. Hormonal tests reveal normal or high serum concentrations of GH. IGF-1 and growth hormone binding protein (GHBP) levels depend on the disease-causing mutations. IGF-1 levels are low in cases ofGHR defects, STAT5b, IGF-1 and ALS deficiencies, and high in cases of IGF-1 resistance. GHBP levels are low in cases of mutations in the extracellular domain of GHR and normal in cases of mutations in the intracellular domain of GHR or post receptor defects. IGF-BP 3 levels are low in cases of GHR, STAT5b, and ALS deficiencies, normal in cases of IGF-1 deficiency. ALS levels are low in cases of ALS deficiencies. Genetic tests should be performed to make a precise etiological diagnosis.Differential diagnosisThe differential diagnosis should include secondary IGF-1 deficiency due to nutritional problems or chronic pediatric diseases.Genetic counselingGenetic counseling should be proposed to parents of an affected individual before any further pregnancy, informing them of the risks and the available diagnostic methods.Management and treatmentManagement aims at improving growth and, except for IGF-1 resistance, includes treatment with daily subcutaneous injections of mecasermin, a recombinant human IGF-1, and diet with adequate caloric intake. In August 2005, mecasermin was granted EC orphan drug designation. Growth hormone treatment may partially improve growth in cases of IGF-1 resistance. There is no treatment that cures or prevents the disease.PrognosisWith age, osteoporosis can become apparent. Patients may develop obesity, hypercholesterolemia, insulin resistance, glucose intolerance and even type II diabetes.Visit the Orphanet disease page for more resources.

MalaCards based summary : Growth Hormone Insensitivity with Immunodeficiency, also known as growth hormone insensitivity due to postreceptor defect, is related to laron syndrome. An important gene associated with Growth Hormone Insensitivity with Immunodeficiency is STAT5B (Signal Transducer And Activator Of Transcription 5B), and among its related pathways/superpathways are ErbB signaling pathway and Chemokine signaling pathway. Affiliated tissues include testes, and related phenotypes are growth hormone deficiency and respiratory distress

UniProtKB/Swiss-Prot : 75 Growth hormone insensitivity with immunodeficiency: A disease characterized by short stature, growth hormone deficiency in the presence of normal to elevated circulating concentrations of growth hormone, resistance to hexogeneous growth hormone therapy, and recurrent infections.

Description from OMIM: 245590

Related Diseases for Growth Hormone Insensitivity with Immunodeficiency

Diseases related to Growth Hormone Insensitivity with Immunodeficiency via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 laron syndrome 10.0

Symptoms & Phenotypes for Growth Hormone Insensitivity with Immunodeficiency

Clinical features from OMIM:

245590

Human phenotypes related to Growth Hormone Insensitivity with Immunodeficiency:

32
# Description HPO Frequency HPO Source Accession
1 growth hormone deficiency 32 HP:0000824
2 respiratory distress 32 HP:0002098
3 severe short stature 32 HP:0003510

Drugs & Therapeutics for Growth Hormone Insensitivity with Immunodeficiency

Search Clinical Trials , NIH Clinical Center for Growth Hormone Insensitivity with Immunodeficiency

Genetic Tests for Growth Hormone Insensitivity with Immunodeficiency

Genetic tests related to Growth Hormone Insensitivity with Immunodeficiency:

# Genetic test Affiliating Genes
1 Growth Hormone Insensitivity with Immunodeficiency 29 STAT5B

Anatomical Context for Growth Hormone Insensitivity with Immunodeficiency

MalaCards organs/tissues related to Growth Hormone Insensitivity with Immunodeficiency:

41
Testes

Publications for Growth Hormone Insensitivity with Immunodeficiency

Articles related to Growth Hormone Insensitivity with Immunodeficiency:

# Title Authors Year
1
Laron syndrome due to a post-receptor defect: response to IGF-I treatment. ( 8300382 )
1993

Variations for Growth Hormone Insensitivity with Immunodeficiency

UniProtKB/Swiss-Prot genetic disease variations for Growth Hormone Insensitivity with Immunodeficiency:

75
# Symbol AA change Variation ID SNP ID
1 STAT5B p.Ala630Pro VAR_018728 rs121908501
2 STAT5B p.Phe646Ser VAR_067368

ClinVar genetic disease variations for Growth Hormone Insensitivity with Immunodeficiency:

6
(show all 49)
# Gene Variation Type Significance SNP ID Assembly Location
1 STAT5B NM_012448.3(STAT5B): c.1888G> C (p.Ala630Pro) single nucleotide variant Pathogenic rs121908501 GRCh37 Chromosome 17, 40362207: 40362207
2 STAT5B NM_012448.3(STAT5B): c.1888G> C (p.Ala630Pro) single nucleotide variant Pathogenic rs121908501 GRCh38 Chromosome 17, 42210189: 42210189
3 STAT5B STAT5B, 1-BP INS, 1191G insertion Pathogenic
4 STAT5B STAT5B, 1-BP INS, 1102C insertion Pathogenic
5 STAT5B NM_012448.3(STAT5B): c.454C> T (p.Arg152Ter) single nucleotide variant Pathogenic rs121908502 GRCh37 Chromosome 17, 40375496: 40375496
6 STAT5B NM_012448.3(STAT5B): c.454C> T (p.Arg152Ter) single nucleotide variant Pathogenic rs121908502 GRCh38 Chromosome 17, 42223478: 42223478
7 STAT5B STAT5B, 1-BP DEL, EXON 13/INTRON 13 JUNCTION deletion Pathogenic
8 STAT5B NM_012448.3(STAT5B): c.1101C> A (p.Pro367=) single nucleotide variant Benign rs61749920 GRCh37 Chromosome 17, 40370237: 40370237
9 STAT5B NM_012448.3(STAT5B): c.1101C> A (p.Pro367=) single nucleotide variant Benign rs61749920 GRCh38 Chromosome 17, 42218219: 42218219
10 STAT5B NM_012448.3(STAT5B): c.993G> A (p.Thr331=) single nucleotide variant Benign rs59491077 GRCh37 Chromosome 17, 40370345: 40370345
11 STAT5B NM_012448.3(STAT5B): c.993G> A (p.Thr331=) single nucleotide variant Benign rs59491077 GRCh38 Chromosome 17, 42218327: 42218327
12 STAT5B NM_012448.3(STAT5B): c.247C> T (p.Leu83=) single nucleotide variant Benign rs146176992 GRCh37 Chromosome 17, 40379585: 40379585
13 STAT5B NM_012448.3(STAT5B): c.247C> T (p.Leu83=) single nucleotide variant Benign rs146176992 GRCh38 Chromosome 17, 42227567: 42227567
14 STAT5B NM_012448.3(STAT5B): c.1569G> A (p.Arg523=) single nucleotide variant Conflicting interpretations of pathogenicity rs143172354 GRCh37 Chromosome 17, 40364113: 40364113
15 STAT5B NM_012448.3(STAT5B): c.1569G> A (p.Arg523=) single nucleotide variant Conflicting interpretations of pathogenicity rs143172354 GRCh38 Chromosome 17, 42212095: 42212095
16 STAT5B NM_012448.3(STAT5B): c.690C> T (p.Ala230=) single nucleotide variant Benign rs555155085 GRCh38 Chromosome 17, 42219455: 42219455
17 STAT5B NM_012448.3(STAT5B): c.690C> T (p.Ala230=) single nucleotide variant Benign rs555155085 GRCh37 Chromosome 17, 40371473: 40371473
18 STAT5B NM_012448.3(STAT5B): c.1596C> A (p.Phe532Leu) single nucleotide variant Uncertain significance GRCh38 Chromosome 17, 42212068: 42212068
19 STAT5B NM_012448.3(STAT5B): c.1596C> A (p.Phe532Leu) single nucleotide variant Uncertain significance GRCh37 Chromosome 17, 40364086: 40364086
20 STAT5B NM_012448.3(STAT5B): c.2185G> T (p.Ala729Ser) single nucleotide variant Likely benign rs200042237 GRCh37 Chromosome 17, 40354410: 40354410
21 STAT5B NM_012448.3(STAT5B): c.2185G> T (p.Ala729Ser) single nucleotide variant Likely benign rs200042237 GRCh38 Chromosome 17, 42202392: 42202392
22 STAT5B NM_012448.3(STAT5B): c.1725C> T (p.Asp575=) single nucleotide variant Benign rs75130700 GRCh37 Chromosome 17, 40362471: 40362471
23 STAT5B NM_012448.3(STAT5B): c.1725C> T (p.Asp575=) single nucleotide variant Benign rs75130700 GRCh38 Chromosome 17, 42210453: 42210453
24 STAT5B NM_012448.3(STAT5B): c.1421A> G (p.Gln474Arg) single nucleotide variant Pathogenic GRCh38 Chromosome 17, 42216066: 42216066
25 STAT5B NM_012448.3(STAT5B): c.1421A> G (p.Gln474Arg) single nucleotide variant Pathogenic GRCh37 Chromosome 17, 40368084: 40368084
26 STAT5B NM_012448.3(STAT5B): c.1433C> T (p.Ala478Val) single nucleotide variant Pathogenic GRCh38 Chromosome 17, 42216054: 42216054
27 STAT5B NM_012448.3(STAT5B): c.1433C> T (p.Ala478Val) single nucleotide variant Pathogenic GRCh37 Chromosome 17, 40368072: 40368072
28 STAT5B NM_012448.3(STAT5B): c.530A> C (p.Gln177Pro) single nucleotide variant Pathogenic GRCh38 Chromosome 17, 42223402: 42223402
29 STAT5B NM_012448.3(STAT5B): c.530A> C (p.Gln177Pro) single nucleotide variant Pathogenic GRCh37 Chromosome 17, 40375420: 40375420
30 STAT5B NM_012448.3(STAT5B): c.798G> C (p.Gly266=) single nucleotide variant Likely benign GRCh37 Chromosome 17, 40371365: 40371365
31 STAT5B NM_012448.3(STAT5B): c.798G> C (p.Gly266=) single nucleotide variant Likely benign GRCh38 Chromosome 17, 42219347: 42219347
32 STAT5B NM_012448.3(STAT5B): c.1408G> A (p.Val470Ile) single nucleotide variant Uncertain significance GRCh38 Chromosome 17, 42216079: 42216079
33 STAT5B NM_012448.3(STAT5B): c.1408G> A (p.Val470Ile) single nucleotide variant Uncertain significance GRCh37 Chromosome 17, 40368097: 40368097
34 STAT5B NM_012448.3(STAT5B): c.561C> T (p.Gly187=) single nucleotide variant Likely benign GRCh37 Chromosome 17, 40371850: 40371850
35 STAT5B NM_012448.3(STAT5B): c.561C> T (p.Gly187=) single nucleotide variant Likely benign GRCh38 Chromosome 17, 42219832: 42219832
36 STAT5B NM_012448.3(STAT5B): c.551-5T> C single nucleotide variant Benign rs200299299 GRCh37 Chromosome 17, 40371865: 40371865
37 STAT5B NM_012448.3(STAT5B): c.551-5T> C single nucleotide variant Benign rs200299299 GRCh38 Chromosome 17, 42219847: 42219847
38 STAT5B NM_012448.3(STAT5B): c.2292C> T (p.Asp764=) single nucleotide variant Likely benign rs146467656 GRCh38 Chromosome 17, 42201810: 42201810
39 STAT5B NM_012448.3(STAT5B): c.2292C> T (p.Asp764=) single nucleotide variant Likely benign rs146467656 GRCh37 Chromosome 17, 40353828: 40353828
40 STAT5B NM_012448.3(STAT5B): c.1591G> A (p.Val531Met) single nucleotide variant Uncertain significance rs142918872 GRCh37 Chromosome 17, 40364091: 40364091
41 STAT5B NM_012448.3(STAT5B): c.1591G> A (p.Val531Met) single nucleotide variant Uncertain significance rs142918872 GRCh38 Chromosome 17, 42212073: 42212073
42 STAT5B NM_012448.3(STAT5B): c.691G> A (p.Glu231Lys) single nucleotide variant Uncertain significance rs917567542 GRCh38 Chromosome 17, 42219454: 42219454
43 STAT5B NM_012448.3(STAT5B): c.691G> A (p.Glu231Lys) single nucleotide variant Uncertain significance rs917567542 GRCh37 Chromosome 17, 40371472: 40371472
44 STAT5B NM_012448.3(STAT5B): c.550+7C> A single nucleotide variant Likely benign rs771507023 GRCh37 Chromosome 17, 40375393: 40375393
45 STAT5B NM_012448.3(STAT5B): c.550+7C> A single nucleotide variant Likely benign rs771507023 GRCh38 Chromosome 17, 42223375: 42223375
46 STAT5B NM_012448.3(STAT5B): c.429G> C (p.Gln143His) single nucleotide variant Likely benign rs148793995 GRCh37 Chromosome 17, 40375521: 40375521
47 STAT5B NM_012448.3(STAT5B): c.429G> C (p.Gln143His) single nucleotide variant Likely benign rs148793995 GRCh38 Chromosome 17, 42223503: 42223503
48 STAT5B NM_012448.3(STAT5B): c.319C> T (p.Arg107Cys) single nucleotide variant Uncertain significance GRCh37 Chromosome 17, 40376853: 40376853
49 STAT5B NM_012448.3(STAT5B): c.319C> T (p.Arg107Cys) single nucleotide variant Uncertain significance GRCh38 Chromosome 17, 42224835: 42224835

Expression for Growth Hormone Insensitivity with Immunodeficiency

Search GEO for disease gene expression data for Growth Hormone Insensitivity with Immunodeficiency.

Pathways for Growth Hormone Insensitivity with Immunodeficiency

Pathways related to Growth Hormone Insensitivity with Immunodeficiency according to KEGG:

37
# Name Kegg Source Accession
1 ErbB signaling pathway hsa04012
2 Chemokine signaling pathway hsa04062
3 Jak-STAT signaling pathway hsa04630

GO Terms for Growth Hormone Insensitivity with Immunodeficiency

Sources for Growth Hormone Insensitivity with Immunodeficiency

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
Content
Loading form....