Congenital Hypopituitarism

Categories: Cardiovascular diseases, Endocrine diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Congenital Hypopituitarism

MalaCards integrated aliases for Congenital Hypopituitarism:

Name: Congenital Hypopituitarism 20 58
Non-Acquired Combined Pituitary Hormone Deficiency 20 58
Congenital Combined Pituitary Hormone Deficiency 20 58


Orphanet epidemiological data:

non-acquired combined pituitary hormone deficiency
Prevalence: 1-5/10000 (Europe); Age of onset: All ages; Age of death: normal life expectancy;


Orphanet: 58  
Rare endocrine diseases

External Ids:

ICD10 via Orphanet 33 E23.0
Orphanet 58 ORPHA467

Summaries for Congenital Hypopituitarism

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 467 Definition Congenital hypopituitarism is characterized by multiple pituitary hormone deficiency, including somatotroph, thyrotroph, lactotroph, corticotroph or gonadotroph deficiencies, due to mutations of pituitary transcription factors involved in pituitary ontogenesis. Epidemiology Congenital hypopituitarism is rare compared with the high incidence of hypopituitarism induced by pituitary adenomas, transsphenoidal surgery or radiotherapy. The incidence of congenital hypopituitarism is estimated to be between 1:3000 and 1:4000 births. Clinical description Clinical presentation is variable, depending on the type and severity of deficiencies and on the age at diagnosis. If untreated, main symptoms include short stature, cognitive alterations or delayed puberty. Etiology Congenital hypopituitarism is due to mutations of several genes encoding pituitary transcription factors. Phenotype varies with the factor involved: PROP1 (somatolactotroph, thyrotroph, gonadotroph and sometimes corticotroph deficiencies; pituitary hyper and hypoplasia), POU1F1 (somatolactotroph and thyrotroph deficiencies, pituitary hypoplasia), HESX1 (variable pituitary deficiencies, septo-optic dysplasia), and less frequently LHX3 (somatolactotroph, thyrotroph and gonadotroph deficiencies, limited head and neck rotation) and LHX4 (variable pituitary deficiencies, ectopic neurohypophysis, cerebral abnormalities). Diagnostic methods A diagnosis of combined pituitary hormone deficiency (CPHD) must be suspected when evident causes of hypopituitarism (sellar tumor, postsurgical or radioinduced hypopituitarism...) have been ruled out. Clinical, biological and radiological work-up is very important to better determine which transcription factor should be screened. Confirmation is provided by direct sequencing of the transcription factor genes. Genetic counseling Type of transmission varies with the factor and the mutation involved (recessive transmission for PROP1 and LHX3, dominant for LHX4, autosomal or recessive for POU1F1 and HESX1). Management and treatment An appropriate replacement of hormone deficiencies is required. Strict follow-up is necessary because patients develop new deficiencies (for example late onset corticotroph deficiency in patients with PROP1 mutations). Prognosis Prognosis is equivalent to patients without pituitary deficiencies if treatment is started immediately when diagnosis is confirmed, and if a specialized follow-up is performed.

MalaCards based summary : Congenital Hypopituitarism, also known as non-acquired combined pituitary hormone deficiency, is related to combined pituitary hormone deficiencies, genetic forms and growth hormone deficiency. An important gene associated with Congenital Hypopituitarism is PROP1 (PROP Paired-Like Homeobox 1). Affiliated tissues include pituitary, hypothalamus and bone marrow, and related phenotypes are endocrine/exocrine gland and nervous system

Related Diseases for Congenital Hypopituitarism

Diseases in the Hypopituitarism family:

Congenital Hypopituitarism

Diseases related to Congenital Hypopituitarism via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 101)
# Related Disease Score Top Affiliating Genes
1 combined pituitary hormone deficiencies, genetic forms 30.8 PROP1 LHX4 HESX1 GLI2
2 growth hormone deficiency 30.3 HESX1 GHRH
3 pituitary hypoplasia 30.0 LHX4 HESX1
4 hypopituitarism 29.6 PROP1 LHX4 HESX1 GLI2 GHRH
5 pituitary stalk interruption syndrome 29.6 LHX4 HESX1
6 cryptorchidism, unilateral or bilateral 29.5 PROP1 LHX4 HESX1
7 hypothyroidism 29.4 PROP1 LHX4 HESX1 GHRH
8 congenital hypothyroidism 29.4 PROP1 LHX4 HESX1
9 isolated growth hormone deficiency 29.2 PROP1 LHX4 HESX1 GHRH
10 holoprosencephaly 29.1 PROP1 LHX4 HESX1 GLI2
11 septooptic dysplasia 28.9 PROP1 LHX4 HESX1 GLI2 GHRH
12 pituitary hormone deficiency, combined, 2 28.8 PROP1 LHX4 HESX1 GLI2 GHRH
13 pituitary gland disease 28.7 PROP1 LHX4 HESX1 GHRH
14 pituitary hormone deficiency, combined, 3 12.0
15 disease associated with non-acquired combined pituitary hormone deficiency 11.5
16 central congenital hypothyroidism 11.0
17 hypoglycemia 10.5
18 cholestasis 10.2
19 penis agenesis 10.2
20 optic nerve hypoplasia, bilateral 10.1
21 diabetes insipidus 10.1
22 hypogonadotropic hypogonadism 7 with or without anosmia 10.1
23 biliary atresia 10.1
24 neonatal jaundice 10.1
25 isolated gonadotropin-releasing hormone deficiency 10.1
26 cleft palate, isolated 10.0
27 bilirubin metabolic disorder 10.0
28 prop1-related combined pituitary hormone deficiency 10.0
29 absence of septum pellucidum 10.0
30 strabismus 9.9
31 fryns microphthalmia syndrome 9.9
32 culler-jones syndrome 9.9
33 metabolic acidosis 9.9
34 microphthalmia 9.9
35 dilated cardiomyopathy 9.9
36 amenorrhea 9.9
37 hypogonadism 9.9
38 mechanical strabismus 9.9
39 48,xyyy 9.9
40 posttransplant acute limbic encephalitis 9.9
41 pituitary hormone deficiency, combined, 1 9.9 LHX4 HESX1
42 adamantinous craniopharyngioma 9.9 PROP1 HESX1
43 isolated growth hormone deficiency type iii 9.8 HESX1 GHRH
44 atrial standstill 1 9.8
45 fibromatosis, gingival, with progressive deafness 9.8
46 prader-willi syndrome 9.8
47 trichorhinophalangeal syndrome, type i 9.8
48 glycogen storage disease ia 9.8
49 hypopituitarism, congenital, with central diabetes insipidus 9.8
50 shwachman-diamond syndrome 1 9.8

Graphical network of the top 20 diseases related to Congenital Hypopituitarism:

Diseases related to Congenital Hypopituitarism

Symptoms & Phenotypes for Congenital Hypopituitarism

MGI Mouse Phenotypes related to Congenital Hypopituitarism:

# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.55 GHRH GLI2 HESX1 LHX4 PROP1
2 nervous system MP:0003631 9.35 GHRH GLI2 HESX1 LHX4 PROP1
3 respiratory system MP:0005388 8.92 GLI2 HESX1 LHX4 PROP1

Drugs & Therapeutics for Congenital Hypopituitarism

Search Clinical Trials , NIH Clinical Center for Congenital Hypopituitarism

Genetic Tests for Congenital Hypopituitarism

Anatomical Context for Congenital Hypopituitarism

MalaCards organs/tissues related to Congenital Hypopituitarism:

Pituitary, Hypothalamus, Bone Marrow, Whole Blood, Heart, Kidney

Publications for Congenital Hypopituitarism

Articles related to Congenital Hypopituitarism:

(show top 50) (show all 194)
# Title Authors PMID Year
Congenital hypopituitarism in two brothers with a duplication of the 'acrogigantism gene' GPR101: clinical findings and review of the literature. 61
33184694 2021
Comprehensive identification of pathogenic gene variants in patients with neuroendocrine disorders. 61
33729509 2021
Endocrine dysfunction in children with Shwachman-Diamond syndrome. 61
33619711 2021
Clinical Evaluation of a Custom Gene Panel as a Tool for Precision Male Infertility Diagnosis by Next-Generation Sequencing. 61
33076341 2020
Isolated Fetal Sinus Bradycardia as a First Sign of Congenital Hypopituitarism. 61
32995728 2020
Disrupted Hypothalamo-Pituitary Axis in Association With Reduced SHH Underlies the Pathogenesis of NOTCH-Deficiency. 61
32403133 2020
Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood. 61
32415500 2020
The Molecular Basis of Congenital Hypopituitarism and Related Disorders. 61
31702014 2020
Current management of congenital anterior cranial base encephaloceles. 61
31931391 2020
Development of the Pituitary Gland. 61
32163208 2020
Hypopituitarism in Patients with Blepharophimosis and FOXL2 Mutations. 61
32454486 2020
Congenital Hypopituitarism During the Neonatal Period: Epidemiology, Pathogenesis, Therapeutic Options, and Outcome. 61
33634051 2020
NBPF9 Gene May Be Involved in Congenital Hypopituitarism: A Whole-Genome Study of a Boy with Pituitary Stalk Interruption Syndrome and His Family. 61
32733554 2020
Delayed diagnosis of congenital hypopituitarism associated with low socio-economic status and/or migration. 61
31691850 2020
Mutations in MAGEL2 and L1CAM Are Associated With Congenital Hypopituitarism and Arthrogryposis. 61
31504653 2019
Osteonecrosis of Femoral Head is Associated with Congenital Multiple Pituitary Hormone Deficiency: Report of Three Cases and Literature Review. 61
30966827 2019
Loss of function BMP4 mutation supports the implication of the BMP/TGF-β pathway in the etiology of combined pituitary hormone deficiency. 61
31120642 2019
Truncating RAX Mutations: Anophthalmia, Hypopituitarism, Diabetes Insipidus, and Cleft Palate in Mice and Men. 61
30811539 2019
Severe, persistent neonatal hypoglycemia as a presenting feature in patients with congenital hypopituitarism: a review of our case series. 61
31211689 2019
Genetic diagnosis of congenital hypopituitarism by a target gene panel: novel pathogenic variants in GLI2, OTX2 and GHRHR. 61
30959475 2019
Exome sequencing identifies a de novo FOXA2 variant in a patient with syndromic diabetes. 61
30684292 2019
Liver Involvement in Congenital Hypopituitarism. 61
30666560 2019
Prolonged neonatal hyperbilirubinaemia in a case of congenital hypopituitarism. 61
30737331 2019
Congenital Hypopituitarism: Various Genes, Various Phenotypes. 61
30759489 2019
A novel GLI2 mutation responsible for congenital hypopituitarism and polymalformation syndrome. 61
30583238 2019
Xq27.1 Duplication Encompassing SOX3: Variable Phenotype and Smallest Duplication Associated with Hypopituitarism to Date - A Large Case Series of Unrelated Patients and a Literature Review. 61
31678974 2019
Genome-wide methylation study of whole blood cells DNA in men with congenital hypopituitarism disease. 61
30365064 2019
Slipped capital femoral epiphysis in an adult with congenital hypopituitarism: A case report. 61
30653105 2019
Reduced Hepatocellular Expression of Canalicular Transport Proteins in Infants with Neonatal Cholestasis and Congenital Hypopituitarism. 61
29935878 2018
Identification of SLC20A1 and SLC15A4 among other genes as potential risk factors for combined pituitary hormone deficiency. 61
29261175 2018
Next generation sequencing panel based on single molecule molecular inversion probes for detecting genetic variants in children with hypopituitarism. 61
29739035 2018
Pituitary stalk interruption syndrome presenting in a euthyroid adult with short stature. 61
29904499 2018
Congenital hypopituitarism: how to select the patients for genetic analyses. 61
29625578 2018
Congenital Hypopituitarism. 61
29406008 2018
Pathogenic copy number variants in patients with congenital hypopituitarism associated with complex phenotypes. 61
29265571 2018
The central diabetes insipidus associated with septo-optic dysplasia (de Morsier syndrome). 61
30963758 2018
Impact of etiology, age and gender on onset and severity of hyponatremia in patients with hypopituitarism: retrospective analysis in a specialised endocrine unit. 61
28913704 2017
Novel FOXA2 mutation causes Hyperinsulinism, Hypopituitarism with Craniofacial and Endoderm-derived organ abnormalities. 61
28973288 2017
The Missing Link: A Case of Absent Pituitary Infundibulum and Ectopic Neurohypophysis in a Pediatric Patient with Heterotaxy Syndrome. 61
29299107 2017
A heterozygous microdeletion of 20p12.2-3 encompassing PROKR2 and BMP2 in a patient with congenital hypopituitarism and growth hormone deficiency. 61
28586151 2017
Rare Frequency of Mutations in Pituitary Transcription Factor Genes in Combined Pituitary Hormone or Isolated Growth Hormone Deficiencies in Korea. 61
28332357 2017
A Case of Congenital Hypopituitarism Associated With a 1p31 Microdeletion: A Possible Role for LEPR and JAK1. 61
29264484 2017
Cholestasis and hypercalcemia secondary to panhypopituitarism in a newborn. 61
29168375 2017
Pilot Neonatal Screening Program for Central Congenital Hypothyroidism: Evidence of Significant Detection. 61
28898885 2017
Contribution of LHX4 Mutations to Pituitary Deficits in a Cohort of 417 Unrelated Patients. 61
27820671 2017
Foxo1 Is Required for Normal Somatotrope Differentiation. 61
27631552 2016
A unique case of Shwachman-Diamond syndrome presenting with congenital hypopituitarism. 61
27754968 2016
A patient with pseudohypoaldosteronism type II complicated by congenital hypopituitarism carrying a KLHL3 mutation. 61
27780982 2016
HESX1 mutations in patients with congenital hypopituitarism: variable phenotypes with the same genotype. 61
27000987 2016
Two coexisting heterozygous frameshift mutations in PROP1 are responsible for a different phenotype of combined pituitary hormone deficiency. 61
26608600 2016

Variations for Congenital Hypopituitarism

Expression for Congenital Hypopituitarism

Search GEO for disease gene expression data for Congenital Hypopituitarism.

Pathways for Congenital Hypopituitarism

GO Terms for Congenital Hypopituitarism

Biological processes related to Congenital Hypopituitarism according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of transcription by RNA polymerase II GO:0006357 9.26 PROP1 LHX4 HESX1 GLI2
2 pituitary gland development GO:0021983 8.8 PROP1 HESX1 GLI2

Molecular functions related to Congenital Hypopituitarism according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA binding GO:0003677 9.56 PROP1 LHX4 HESX1 GLI2
2 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000977 9.33 LHX4 HESX1 GLI2
3 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.26 PROP1 LHX4 HESX1 GLI2
4 sequence-specific double-stranded DNA binding GO:1990837 8.92 PROP1 LHX4 HESX1 GLI2

Sources for Congenital Hypopituitarism

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
69 Tocris
71 UMLS via Orphanet
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