Details of Disease

General Information of Disease (ID: DISI019B)

• Disease Name: Pituitary dwarfism
• Definition: Proportionately decreased bodily growth due to failure of the pituitary gland to produce an adequate supply of growth hormone.
• Disease Hierarchy:
  DISFS818: Adrenal gland disorder
  DISI019B: Pituitary dwarfism
• Disease Identifiers:
  MONDO ID: MONDO_0006909
  MESH ID: D004393
  UMLS CUI: C0013338
  MedGen ID: 8506
  HPO ID: HP:0000839
  SNOMED CT ID: 367460001

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Somatropin recombinant	DMF3GM2	Approved	NA	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 11 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GHRHR	TTG4R8V	Limited	Genetic Variation	[2]
GH1	TTT3YKH	Strong	Altered Expression	[3]
GHSR	TTWDC17	Strong	Biomarker	[4]
GLI2	TT045OH	Strong	Genetic Variation	[5]
GNRH1	TT0ID4A	Strong	Biomarker	[6]
GNRHR	TT8R70G	Strong	Biomarker	[7]
GPR101	TTUKZVG	Strong	Genetic Variation	[8]
IGFBP3	TTZHNQA	Strong	Biomarker	[3]
KISS1	TTU2O6T	Strong	Biomarker	[9]
KISS1R	TT3KBZY	Strong	Biomarker	[10]
TACR3	TTBPGLU	Strong	Biomarker	[11]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC20A1	DTMULXV	Strong	Genetic Variation	[12]

This Disease Is Related to 15 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
HESX1	OT5E2Z4G	Limited	Genetic Variation	[13]
POU1F1	OTXT8A5C	Limited	Genetic Variation	[14]
RNPC3	OTW5MKC1	Limited	Genetic Variation	[15]
OTX2	OTTV05B1	Disputed	Biomarker	[16]
GHRH	OT94U6MO	moderate	Genetic Variation	[17]
CSHL1	OTQKU2F5	Strong	Biomarker	[18]
FBRS	OTUVH446	Strong	Genetic Variation	[19]
FBXO8	OTZNGJGW	Strong	Genetic Variation	[19]
HGH1	OTY4H7ZZ	Strong	Genetic Variation	[20]
LHX3	OTQ5BAJ9	Strong	Biomarker	[4]
LHX4	OTVX3J6S	Strong	Genetic Variation	[21]
PHEX	OTG7N3J7	Strong	Biomarker	[22]
PROP1	OT8GF6N8	Strong	Biomarker	[4]
SOX3	OT1CRCOB	Strong	Genetic Variation	[23]
TG	OT3ELHIJ	Strong	Biomarker	[24]

References

• [1] Efficacy and Safety of Weekly Somatrogon vs Daily Somatropin in Children With Growth Hormone Deficiency: A Phase 3 Study. J Clin Endocrinol Metab. 2022 Jun 16;107(7):e2717-e2728.
• [2] Walking and postural balance in adults with severe short stature due to isolated GH deficiency.Endocr Connect. 2019 Apr;8(4):416-424. doi: 10.1530/EC-19-0103.
• [3] p.R209H GH1 variant challenges short stature assessment.Growth Horm IGF Res. 2020 Feb;50:23-26. doi: 10.1016/j.ghir.2019.11.002. Epub 2019 Dec 3.
• [4] Molecular screening of a large cohort of Moroccan patients with congenital hypopituitarism.Clin Endocrinol (Oxf). 2015 Jun;82(6):876-84. doi: 10.1111/cen.12706. Epub 2015 Feb 6.
• [5] Two novel heterozygous missense variations within the GLI2 gene in two unrelated Argentine patients.Medicina (B Aires). 2016;76(4):213-8.
• [6] Sertoli cell androgen receptor DNA binding domain is essential for the completion of spermatogenesis.Endocrinology. 2009 Oct;150(10):4755-65. doi: 10.1210/en.2009-0416. Epub 2009 Jul 2.
• [7] A novel mouse model of hypogonadotrophic hypogonadism: N-ethyl-N-nitrosourea-induced gonadotropin-releasing hormone receptor gene mutation.Mol Endocrinol. 2005 Apr;19(4):972-81. doi: 10.1210/me.2004-0192. Epub 2004 Dec 29.
• [8] GPR101 Mutations are not a Frequent Cause of Congenital Isolated Growth Hormone Deficiency.Horm Metab Res. 2016 Jun;48(6):389-93. doi: 10.1055/s-0042-100733. Epub 2016 Jan 21.
• [9] Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene.Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10714-9. doi: 10.1073/pnas.0704114104. Epub 2007 Jun 11.
• [10] Kisspeptin signaling is indispensable for neurokinin B, but not glutamate, stimulation of gonadotropin secretion in mice.Endocrinology. 2012 Jan;153(1):316-28. doi: 10.1210/en.2011-1260. Epub 2011 Nov 8.
• [11] Uncovering novel reproductive defects in neurokinin B receptor null mice: closing the gap between mice and men.Endocrinology. 2012 Mar;153(3):1498-508. doi: 10.1210/en.2011-1949. Epub 2012 Jan 17.
• [12] Description of a Brazilian patient bearing the R271W Pit-1 gene mutation.Thyroid. 1998 Apr;8(4):299-304. doi: 10.1089/thy.1998.8.299.
• [13] HESX1 mutations in patients with congenital hypopituitarism: variable phenotypes with the same genotype.Clin Endocrinol (Oxf). 2016 Sep;85(3):408-14. doi: 10.1111/cen.13067. Epub 2016 Apr 28.
• [14] Functional characterization of a human POU1F1 mutation associated with isolated growth hormone deficiency: a novel etiology for IGHD. Hum Mol Genet. 2016 Feb 1;25(3):472-83. doi: 10.1093/hmg/ddv486. Epub 2015 Nov 26.
• [15] Mutations in the U11/U12-65K protein associated with isolated growth hormone deficiency lead to structural destabilization and impaired binding of U12 snRNA.RNA. 2018 Mar;24(3):396-409. doi: 10.1261/rna.062844.117. Epub 2017 Dec 18.
• [16] A novel OTX2 mutation in a patient with combined pituitary hormone deficiency, pituitary malformation, and an underdeveloped left optic nerve.Eur J Endocrinol. 2012 Sep;167(3):441-52. doi: 10.1530/EJE-12-0333. Epub 2012 Jun 19.
• [17] Behavioural phenotyping, learning and memory in young and aged growth hormone-releasing hormone-knockout mice.Endocr Connect. 2018 Aug 1;7(8):924-931. doi: 10.1530/EC-18-0165.
• [18] A novel missense mutation in the mouse growth hormone gene causes semidominant dwarfism, hyperghrelinemia, and obesity.Endocrinology. 2004 May;145(5):2531-41. doi: 10.1210/en.2003-1125. Epub 2004 Jan 15.
• [19] Molecular genetic studies in isolated growth hormone deficiency (IGHD).Indian J Pediatr. 2013 Aug;80(8):623-30. doi: 10.1007/s12098-013-0982-2. Epub 2013 Feb 23.
• [20] The use of the polymerase chain reaction in prenatal diagnosis of growth hormone gene deletions.Clin Endocrinol (Oxf). 1992 Jul;37(1):89-95. doi: 10.1111/j.1365-2265.1992.tb02288.x.
• [21] Contribution of LHX4 Mutations to Pituitary Deficits in a Cohort of 417 Unrelated Patients.J Clin Endocrinol Metab. 2017 Jan 1;102(1):290-301. doi: 10.1210/jc.2016-3158.
• [22] X-linked hypogammaglobulinemia and isolated growth hormone deficiency: an update. Immunol Res. 2008;40(3):262-70. doi: 10.1007/s12026-007-0028-9.
• [23] A complex phenotype in a family with a pathogenic SOX3 missense variant.Eur J Med Genet. 2018 Mar;61(3):168-172. doi: 10.1016/j.ejmg.2017.11.012. Epub 2017 Nov 24.
• [24] A novel missense mutation (G2320R) in thyroglobulin causes hypothyroidism in rdw rats.Endocrinology. 2000 Nov;141(11):4050-5. doi: 10.1210/endo.141.11.7794.