KEGG DISEASE: Combined pituitary hormone deficiency

DISEASE: Combined pituitary hormone deficiency

Entry

H02036                      Disease

Name

Combined pituitary hormone deficiency

Supergrp

Growth hormone deficiency [DS:H00254]
Hypopituitarism [DS:H01700]

Description

Combined pituitary hormone deficiency (CPHD) is a rare disorder that is characterized by the impaired production of growth hormone (GH) and one or more other pituitary hormones. Currently reported genes include PROP1, POU1F1, HESX1, LHX3, LHX4, and OTX2. Mutations of these transcription factor genes cause a wide range of pituitary phenotypes, from severe life-threatening CPHD to isolated GH deficiency.

Category

Endocrine and metabolic disease

Brite

Human diseases in ICD-11 classification [BR:br08403]
05 Endocrine, nutritional or metabolic diseases
  Endocrine diseases
   Disorders of the pituitary hormone system
    5A61  Hypofunction or certain other specified disorders of pituitary gland
     H02036  Combined pituitary hormone deficiency
Pathway-based classification of diseases [BR:br08402]
Endocrine system
  nt06324  GHRH-GH-IGF signaling
   H02036  Combined pituitary hormone deficiency

Pathway

hsa04935

Growth hormone synthesis, secretion and action

hsa04550

Signaling pathways regulating pluripotency of stem cells

Network

nt06324 GHRH-GH-IGF signaling

Gene

(CPHD1) POU1F1 [HSA:5449] [KO:K09363]
(CPHD2) PROP1 [HSA:5626] [KO:K09327]
(CPHD3) LHX3 [HSA:8022] [KO:K09374]
(CPHD4) LHX4 [HSA:89884] [KO:K09374]
(CPHD5) HESX1 [HSA:8820] [KO:K09354]
(CPHD6) OTX2 [HSA:5015] [KO:K18490]
(CPHD7) RNPC3 [HSA:55599] [KO:K13157]
(CPHD8) ROBO1 [HSA:6091] [KO:K06753]

Other DBs

ICD-11:

5A61.0

ICD-10:

E23.0

MeSH:

D004393

OMIM:

613038 262600 221750 262700 182230 613986 618160 620303

Reference

PMID:26147833

Authors

De Rienzo F, Mellone S, Bellone S, Babu D, Fusco I, Prodam F, Petri A, Muniswamy R, De Luca F, Salerno M, Momigliano-Richardi P, Bona G, Giordano M

Title

Frequency of genetic defects in combined pituitary hormone deficiency: a systematic review and analysis of a multicentre Italian cohort.

Journal

Clin Endocrinol (Oxf) 83:849-60 (2015)
DOI:10.1111/cen.12849

Reference

PMID:15928241 (CPHD1)

Authors

Turton JP, Reynaud R, Mehta A, Torpiano J, Saveanu A, Woods KS, Tiulpakov A, Zdravkovic V, Hamilton J, Attard-Montalto S, Parascandalo R, Vella C, Clayton PE, Shalet S, Barton J, Brue T, Dattani MT

Title

Novel mutations within the POU1F1 gene associated with variable combined pituitary hormone deficiency.

Journal

J Clin Endocrinol Metab 90:4762-70 (2005)
DOI:10.1210/jc.2005-0570

Reference

PMID:11549703 (CPHD2)

Authors

Vallette-Kasic S, Barlier A, Teinturier C, Diaz A, Manavela M, Berthezene F, Bouchard P, Chaussain JL, Brauner R, Pellegrini-Bouiller I, Jaquet P, Enjalbert A, Brue T

Title

PROP1 gene screening in patients with multiple pituitary hormone deficiency reveals two sites of hypermutability and a high incidence of corticotroph deficiency.

Journal

J Clin Endocrinol Metab 86:4529-35 (2001)
DOI:10.1210/jcem.86.9.7811

Reference

PMID:17327381 (CPHD3)

Authors

Pfaeffle RW, Savage JJ, Hunter CS, Palme C, Ahlmann M, Kumar P, Bellone J, Schoenau E, Korsch E, Bramswig JH, Stobbe HM, Blum WF, Rhodes SJ

Title

Four novel mutations of the LHX3 gene cause combined pituitary hormone deficiencies with or without limited neck rotation.

Journal

J Clin Endocrinol Metab 92:1909-19 (2007)
DOI:10.1210/jc.2006-2177

Reference

PMID:11567216 (CPHD4)

Authors

Machinis K, Pantel J, Netchine I, Leger J, Camand OJ, Sobrier ML, Dastot-Le Moal F, Duquesnoy P, Abitbol M, Czernichow P, Amselem S

Title

Syndromic short stature in patients with a germline mutation in the LIM homeobox LHX4.

Journal

Am J Hum Genet 69:961-8 (2001)
DOI:10.1086/323764

Reference

PMID:11136712 (CPHD5)

Authors

Thomas PQ, Dattani MT, Brickman JM, McNay D, Warne G, Zacharin M, Cameron F, Hurst J, Woods K, Dunger D, Stanhope R, Forrest S, Robinson IC, Beddington RS

Title

Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia.

Journal

Hum Mol Genet 10:39-45 (2001)
DOI:10.1093/hmg/10.1.39

Reference

PMID:18728160 (CPHD6)

Authors

Diaczok D, Romero C, Zunich J, Marshall I, Radovick S

Title

A novel dominant negative mutation of OTX2 associated with combined pituitary hormone deficiency.

Journal

J Clin Endocrinol Metab 93:4351-9 (2008)
DOI:10.1210/jc.2008-1189

Reference

PMID:32462814 (CPHD7)

Authors

Verberne EA, Faries S, Mannens MMAM, Postma AV, van Haelst MM

Title

Expanding the phenotype of biallelic RNPC3 variants associated with growth hormone deficiency.

Journal

Am J Med Genet A 182:1952-1956 (2020)
DOI:10.1002/ajmg.a.61632

Reference

PMID:28402530 (CPHD8)

Authors

Bashamboo A, Bignon-Topalovic J, Moussi N, McElreavey K, Brauner R

Title

Mutations in the Human ROBO1 Gene in Pituitary Stalk Interruption Syndrome.

Journal

J Clin Endocrinol Metab 102:2401-2406 (2017)
DOI:10.1210/jc.2016-1095

LinkDB

» Japanese version

DISEASE: Growth hormone deficiency

Entry

H00254                      Disease

Name

Growth hormone deficiency;
Pituitary dwarfism

Subgroup

Isolated growth hormone deficiency (IGHD) [DS:H02035]
Combined pituitary hormone deficiency (CPHD) [DS:H02036]
Laron syndrome (PD2) [DS:H02037]
X-linked panhypopituitarism (PHPX) [DS:H02038]
Kowarski syndrome [DS:H02039]
Growth hormone deficiency, isolated partial (GHDP)

Supergrp

Hypopituitarism [DS:H01700]

Description

Growth hormone deficiency, formerly known as Pituitary dwarfism, is a heterogeneous condition characterized by growth retardation with short stature and normal body proportions caused by growth hormone deficiency.

Category

Endocrine and metabolic disease

Brite

Human diseases in ICD-11 classification [BR:br08403]
05 Endocrine, nutritional or metabolic diseases
  Endocrine diseases
   Disorders of the pituitary hormone system
    5A61  Hypofunction or certain other specified disorders of pituitary gland
     H00254  Growth hormone deficiency
Pathway-based classification of diseases [BR:br08402]
Immune system
  nt06537  TCR/BCR signaling
   H00254  Growth hormone deficiency
Endocrine system
  nt06324  GHRH-GH-IGF signaling
   H00254  Growth hormone deficiency

Pathway

hsa04662

B cell receptor signaling pathway

hsa04935

Growth hormone synthesis, secretion and action

hsa04080

Neuroactive ligand-receptor interaction

Network

nt06324 GHRH-GH-IGF signaling
nt06537 TCR/BCR signaling

Gene

(IGHD1A/1B/2) GH1 [HSA:2688] [KO:K05438]
(IGHD3) BTK [HSA:695] [KO:K07370]
(IGHD4) GHRHR [HSA:2692] [KO:K04584]
(CPHD1) POU1F1 [HSA:5449] [KO:K09363]
(CPHD2) PROP1 [HSA:5626] [KO:K09327]
(CPHD3) LHX3 [HSA:8022] [KO:K09374]
(CPHD4) LHX4 [HSA:89884] [KO:K09374]
(CPHD5) HESX1 [HSA:8820] [KO:K09354]
(CPHD6) OTX2 [HSA:5015] [KO:K18490]
(CPHD7/IGHD5) RNPC3 [HSA:55599] [KO:K13157]
(CPHD8) ROBO1 [HSA:6091] [KO:K06753]
(PD2) GHR [HSA:2690] [KO:K05080]
(PHPX) SOX3 [HSA:6658] [KO:K09267]
(GHDP) GHSR [HSA:2693] [KO:K04284]

Drug

Somatropin [DR:D02691]
Somapacitan [DR:D11194]
Somatrogon [DR:D10990]
Lonapegsomatropin [DR:D11486]

Other DBs

ICD-11:

5A61.0 5A61.3

ICD-10:

E23.0

MeSH:

D004393

OMIM:

262400 613038 262500 312000 262650 615925 618157 618160

Reference

PMID:7868072

Authors

Perez Jurado LA, Argente J

Title

Molecular basis of familial growth hormone deficiency.

Journal

Horm Res 42:189-97 (1994)
DOI:10.1159/000184192

Reference

PMID:9799079

Authors

Procter AM, Phillips JA 3rd, Cooper DN

Title

The molecular genetics of growth hormone deficiency.

Journal

Hum Genet 103:255-72 (1998)
DOI:10.1007/s004390050815

Reference

PMID:12201208

Authors

Hayashi Y, Kamijo T, Ogawa M, Seo H

Title

Familial isolated growth hormone deficiency: genetics and pathophysiology.

Journal

Endocr J 49:265-72 (2002)
DOI:10.1507/endocrj.49.265

Reference

PMID:17965963

Authors

Hernandez LM, Lee PD, Camacho-Hubner C

Title

Isolated growth hormone deficiency.

Journal

Pituitary 10:351-7 (2007)
DOI:10.1007/s11102-007-0073-3

Reference

PMID:17336732

Authors

Mullis PE

Title

Genetics of growth hormone deficiency.

Journal

Endocrinol Metab Clin North Am 36:17-36 (2007)
DOI:10.1016/j.ecl.2006.11.010

Reference

PMID:8488849 (GHR)

Authors

Berg MA, Argente J, Chernausek S, Gracia R, Guevara-Aguirre J, Hopp M, Perez-Jurado L, Rosenbloom A, Toledo SP, Francke U

Title

Diverse growth hormone receptor gene mutations in Laron syndrome.

Journal

Am J Hum Genet 52:998-1005 (1993)

Reference

PMID:12428212 (SOX3)

Authors

Laumonnier F, Ronce N, Hamel BC, Thomas P, Lespinasse J, Raynaud M, Paringaux C, Van Bokhoven H, Kalscheuer V, Fryns JP, Chelly J, Moraine C, Briault S

Title

Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency.

Journal

Am J Hum Genet 71:1450-5 (2002)
DOI:10.1086/344661

Reference

PMID:16511605 (GHSR)

Authors

Pantel J, Legendre M, Cabrol S, Hilal L, Hajaji Y, Morisset S, Nivot S, Vie-Luton MP, Grouselle D, de Kerdanet M, Kadiri A, Epelbaum J, Le Bouc Y, Amselem S

Title

Loss of constitutive activity of the growth hormone secretagogue receptor in familial short stature.

Journal

J Clin Invest 116:760-8 (2006)
DOI:10.1172/JCI25303

LinkDB

» Japanese version

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