MCID: PTT041
MIFTS: 47

Pituitary Stalk Interruption Syndrome

Categories: Rare diseases, Endocrine diseases, Neuronal diseases

Aliases & Classifications for Pituitary Stalk Interruption Syndrome

MalaCards integrated aliases for Pituitary Stalk Interruption Syndrome:

Name: Pituitary Stalk Interruption Syndrome 53 59 6 73
Ectopic Neurohypophysis 53 59
Psis 53 59

Characteristics:

Orphanet epidemiological data:

59
pituitary stalk interruption syndrome
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Age of onset: Childhood; Age of death: early childhood;

HPO:

32
pituitary stalk interruption syndrome:
Mortality/Aging death in infancy


Classifications:

Orphanet: 59  
Rare endocrine diseases


Summaries for Pituitary Stalk Interruption Syndrome

NIH Rare Diseases : 53 Pituitary stalk interruption syndrome (PSIS) is a congenital abnormality of the pituitary gland  characterized by the triad of a very thin or interrupted pituitary stalk, a misplaced (ectopic) or absent posterior pituitary and a small or absent anterior pituitary, with permanent growth hormone (GH) deficit. Signs and symptoms in newborns include low blood sugar levels (hypoglycemia), jaundice, congenital abnormalities and small penis (micropenis) and/or testis that are not in the scrotal sac (cryptorchidism). Later in childhood, signs may include short stature, seizures, low arterial pressure (hypotension) and/or intellectual delay. Some people can also have vision problems (septooptic dysplasia) and Fanconi anemia. The cause of this condition is unknown.  Rare mutations in the HESX1, LHX4, OTX2, SOX3, and PROKR2 genes can be the cause in familial cases. The diagnosis is confirmed through MRI showing the characteristic findings. Treatment is based on replacement of deficient hormones, particularly GH, and should be started at birth to avoid hormone deficiencies and intellectual delay.

MalaCards based summary : Pituitary Stalk Interruption Syndrome, also known as ectopic neurohypophysis, is related to combined pituitary hormone deficiency and holoprosencephaly. An important gene associated with Pituitary Stalk Interruption Syndrome is GPR161 (G Protein-Coupled Receptor 161), and among its related pathways/superpathways are Ectoderm Differentiation and Hedgehog Pathway. The drugs Benzocaine and Testosterone have been mentioned in the context of this disorder. Affiliated tissues include pituitary, testis and hypothalamus, and related phenotypes are ectopic posterior pituitary and failure to thrive

Related Diseases for Pituitary Stalk Interruption Syndrome

Diseases related to Pituitary Stalk Interruption Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 60)
# Related Disease Score Top Affiliating Genes
1 combined pituitary hormone deficiency 30.2 HESX1 LHX4 POU1F1
2 holoprosencephaly 29.8 CDON SHH TGIF1
3 growth hormone deficiency 28.6 GH1 GHRHR HESX1 SOX3
4 pituitary hypoplasia 27.2 GHRHR HESX1 LHX4 POU1F1 PRL SOX3
5 pituitary hormone deficiency, combined, 2 26.8 GH1 HESX1 LHX4 POU1F1 PRL SOX3
6 hypopituitarism 26.8 GH1 HESX1 LHX4 POU1F1 PRL SOX3
7 central congenital hypothyroidism 11.2
8 normosmic congenital hypogonadotropic hypogonadism 10.3 PROKR2 WDR11
9 holoprosencephaly 4 10.3 SHH TGIF1
10 central nervous system organ benign neoplasm 10.2 HESX1 PRL
11 hypothyroidism due to deficient transcription factors involved in pituitary development or function 10.2 HESX1 LHX4 POU1F1
12 combined pituitary hormone deficiencies, genetic forms 10.2 HESX1 LHX4 POU1F1
13 pituitary hormone deficiency, combined, 1 10.2 HESX1 LHX4 POU1F1
14 septopreoptic holoprosencephaly 10.1 CDON SHH TGIF1
15 midline interhemispheric variant of holoprosencephaly 10.1 CDON SHH TGIF1
16 growth hormone secreting pituitary adenoma 10.1 GHRHR PRL
17 alobar holoprosencephaly 10.1 CDON SHH TGIF1
18 lobar holoprosencephaly 10.1 CDON SHH TGIF1
19 microform holoprosencephaly 10.1 CDON SHH TGIF1
20 semilobar holoprosencephaly 10.1 CDON SHH TGIF1
21 pneumonia 10.0
22 isolated growth hormone deficiency, type iii 10.0 HESX1 SOX3
23 fibrous dysplasia/mccune-albright syndrome 10.0 GH1 PRL
24 tsh producing pituitary tumor 10.0 GH1 PRL
25 adenohypophysitis 10.0 GH1 PRL
26 isolated growth hormone deficiency, type ib 10.0 GH1 GHRHR
27 kallmann syndrome 10.0 HESX1 PROKR2 WDR11
28 pseudohypoparathyroidism, type ia 10.0 GH1 PRL
29 cholestasis 10.0
30 insulin-like growth factor i 10.0
31 hypothalamic disease 10.0 GH1 PRL
32 pituitary adenoma 1, multiple types 10.0 GH1 PRL
33 gigantism 9.9 GH1 PRL
34 empty sella syndrome 9.9 GH1 PRL
35 hyperpituitarism 9.9 GH1 PRL
36 axenfeld-rieger syndrome, type 1 9.8 HESX1 SHH
37 leukemia 9.8
38 thrombocytopenia 9.8
39 immunoglobulin alpha deficiency 9.8
40 thrombocytopenia due to platelet alloimmunization 9.8
41 adenocarcinoma 9.8
42 arthropathy 9.8
43 pancreatitis 9.8
44 diabetes mellitus, noninsulin-dependent 9.8
45 esterase b 9.8
46 schizophrenia 9.8
47 lung cancer 9.8
48 pancreatic cancer 9.8
49 functioning pituitary adenoma 9.8 GH1 PRL
50 tetrahydrobiopterin deficiency 9.6 GH1 PRL

Graphical network of the top 20 diseases related to Pituitary Stalk Interruption Syndrome:



Diseases related to Pituitary Stalk Interruption Syndrome

Symptoms & Phenotypes for Pituitary Stalk Interruption Syndrome

Human phenotypes related to Pituitary Stalk Interruption Syndrome:

59 32 (show all 17)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ectopic posterior pituitary 59 32 obligate (100%) Obligate (100%) HP:0011755
2 failure to thrive 59 32 hallmark (90%) Very frequent (99-80%) HP:0001508
3 short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0004322
4 hypothyroidism 59 32 frequent (33%) Frequent (79-30%) HP:0000821
5 delayed puberty 59 32 frequent (33%) Frequent (79-30%) HP:0000823
6 hypoglycemia 59 32 frequent (33%) Frequent (79-30%) HP:0001943
7 hypoplasia of penis 59 32 frequent (33%) Frequent (79-30%) HP:0008736
8 cryptorchidism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000028
9 primary amenorrhea 59 32 occasional (7.5%) Occasional (29-5%) HP:0000786
10 adrenal hypoplasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000835
11 diabetes insipidus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000873
12 intellectual disability 59 32 occasional (7.5%) Occasional (29-5%) HP:0001249
13 seizures 59 32 occasional (7.5%) Occasional (29-5%) HP:0001250
14 global developmental delay 59 32 occasional (7.5%) Occasional (29-5%) HP:0001263
15 septo-optic dysplasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0100842
16 abnormality of the hypothalamus-pituitary axis 59 Very frequent (99-80%)
17 death in infancy 59 Occasional (29-5%)

MGI Mouse Phenotypes related to Pituitary Stalk Interruption Syndrome:

46 (show all 12)
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.16 PRL GPR161 SHH PROKR2 CDON SOX3
2 growth/size/body region MP:0005378 10.16 GPR161 SHH PROKR2 HESX1 CDON SOX3
3 endocrine/exocrine gland MP:0005379 10.13 SHH PROKR2 HESX1 LHX4 SOX3 POU1F1
4 craniofacial MP:0005382 10.1 GPR161 SHH HESX1 ROBO1 CDON SOX3
5 nervous system MP:0003631 10.1 GPR161 SHH PROKR2 HESX1 ROBO1 CDON
6 homeostasis/metabolism MP:0005376 10.09 ROBO1 PRL TGIF1 PROKR2 SHH LHX4
7 mortality/aging MP:0010768 10.07 GPR161 SHH PROKR2 HESX1 LHX4 CDON
8 reproductive system MP:0005389 9.86 SHH PROKR2 SOX3 POU1F1 GHRHR ROBO1
9 limbs/digits/tail MP:0005371 9.8 TGIF1 GPR161 SHH CDON GHRHR
10 respiratory system MP:0005388 9.63 TGIF1 SHH HESX1 LHX4 CDON ROBO1
11 skeleton MP:0005390 9.5 TGIF1 SHH CDON SOX3 POU1F1 GHRHR
12 taste/olfaction MP:0005394 8.8 TGIF1 SHH HESX1

Drugs & Therapeutics for Pituitary Stalk Interruption Syndrome

Drugs for Pituitary Stalk Interruption Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Benzocaine Approved, Investigational Not Applicable 1994-09-7, 94-09-7 2337
2
Testosterone Approved, Investigational Not Applicable 58-22-0 6013
3 tannic acid Approved, Nutraceutical Not Applicable
4 Hormone Antagonists Not Applicable
5 Hormones Not Applicable
6 Hormones, Hormone Substitutes, and Hormone Antagonists Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Efficacy of Pulsatile GnRH Therapy on Male Patients With Pituitary Stalk Interruption Syndrome Unknown status NCT02705014 Not Applicable Gonadotropin-releasing Hormone

Search NIH Clinical Center for Pituitary Stalk Interruption Syndrome

Genetic Tests for Pituitary Stalk Interruption Syndrome

Anatomical Context for Pituitary Stalk Interruption Syndrome

MalaCards organs/tissues related to Pituitary Stalk Interruption Syndrome:

41
Pituitary, Testis, Hypothalamus

Publications for Pituitary Stalk Interruption Syndrome

Articles related to Pituitary Stalk Interruption Syndrome:

(show all 43)
# Title Authors Year
1
Clues for Polygenic Inheritance of Pituitary Stalk Interruption Syndrome From Exome Sequencing in 20 Patients. ( 29165578 )
2018
2
Pituitary stalk interruption syndrome presenting in a euthyroid adult with short stature. ( 29904499 )
2018
3
Thyrotrophic status in patients with pituitary stalk interruption syndrome. ( 29480822 )
2018
4
Vitamin D in children with growth hormone deficiency due to pituitary stalk interruption syndrome. ( 29368588 )
2018
5
Mutations in the Human ROBO1 Gene in Pituitary Stalk Interruption Syndrome. ( 28402530 )
2017
6
Pituitary stalk interruption syndrome: a rare and severe cause of pituitary deficiency Laboratory diagnosis of a newborn case. ( 28251898 )
2017
7
Digenic Inheritance of PROKR2 and WDR11 Mutations in Pituitary Stalk Interruption Syndrome. ( 28453858 )
2017
8
Delayed diagnosis of pituitary stalk interruption syndrome with severe recurrent hyponatremia caused by adrenal insufficiency. ( 29025209 )
2017
9
Multi-genic pattern found in rare type of hypopituitarism: a whole-exome sequencing study of Han Chinese with pituitary stalk interruption syndrome. ( 28707430 )
2017
10
Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome. ( 28443260 )
2017
11
Pituitary stalk interruption syndrome: cause, clinical manifestations, diagnosis, and management. ( 27386973 )
2016
12
Pituitary Stalk Interruption Syndrome Presenting With Growth Retardation. ( 27238408 )
2016
13
Growth Hormone Therapy Benefits Pituitary Stalk Interruption Syndrome Patients with Short Stature: A Retrospective Study of 75 Han Chinese. ( 27190512 )
2016
14
Pituitary stalk interruption syndrome: From clinical findings to pathogenesis. ( 27917547 )
2016
15
A case of pituitary stalk interruption syndrome with intermittent seizures as the first presentation. ( 28326739 )
2016
16
Clinical Features of Pituitary Stalk Interruption Syndrome in 114 Cases. ( 27825409 )
2016
17
Cholestasis Reveals Severe Cortisol Deficiency in Neonatal Pituitary Stalk Interruption Syndrome. ( 26829045 )
2016
18
Correlation between Pituitary Stalk Interruption Syndrome and Prokineticin Receptor 2 and Prokineticin 2 Mutations. ( 26956854 )
2016
19
A nonsense mutation in the hedgehog receptor CDON associated with pituitary stalk interruption syndrome. ( 26529631 )
2015
20
Pituitary Stalk Interruption Syndrome from Infancy to Adulthood: Clinical, Hormonal, and Radiological Assessment According to the Initial Presentation. ( 26562670 )
2015
21
Relationship between pituitary stalk visibility and the severity of hormone deficiencies: Pituitary stalk interruption syndrome revisited. ( 25845766 )
2015
22
Pituitary stalk interruption syndrome: Case report of three cases with review of literature. ( 25250085 )
2014
23
Whole exome sequencing identifies homozygous GPR161 mutation in a family with pituitary stalk interruption syndrome. ( 25322266 )
2014
24
Pituitary stalk interruption syndrome presenting as short stature: a case report. ( 25524465 )
2014
25
Pituitary stalk interruption syndrome in Chinese people: clinical characteristic analysis of 55 cases. ( 23341953 )
2013
26
Pituitary stalk interruption syndrome and isolated pituitary hypoplasia may be caused by mutations in holoprosencephaly-related genes. ( 23476075 )
2013
27
Pituitary stalk interruption syndrome in 59 children: the value of MRI in assessment of pituitary functions. ( 24257915 )
2013
28
Pituitary stalk interruption syndrome in 53 postpubertal patients: factors influencing the heterogeneity of its presentation. ( 23308160 )
2013
29
Pituitary stalk interruption syndrome in 58 Chinese patients: clinical features and genetic analysis. ( 23199197 )
2013
30
Pituitary stalk interruption syndrome. ( 24617191 )
2013
31
17q21.31 microdeletion in a patient with pituitary stalk interruption syndrome. ( 21397059 )
2011
32
Magnetic resonance image of sellar region in pituitary stalk interruption syndrome in children and adolescents. ( 21375930 )
2011
33
Pituitary stalk interruption syndrome in 83 patients: novel HESX1 mutation and severe hormonal prognosis in malformative forms. ( 21270112 )
2011
34
Pituitary stalk interruption syndrome: diagnostic delay and sensitivity of the auxological criteria of the growth hormone research society. ( 21298012 )
2011
35
Pituitary stalk interruption syndrome: the role of MRI and review of the literature. ( 24148682 )
2010
36
The pituitary stalk interruption syndrome: endocrine features and benefits of growth hormone therapy. ( 20044069 )
2010
37
Diagnosis of growth hormone (GH) deficiency: comparison of pituitary stalk interruption syndrome and transient GH deficiency. ( 19419564 )
2009
38
Gonadotrophic status in adolescents with pituitary stalk interruption syndrome. ( 18088398 )
2008
39
Factors influencing the growth hormone peak and plasma insulin-like growth factor I in young adults with pituitary stalk interruption syndrome. ( 18620575 )
2008
40
Pituitary stalk interruption syndrome (PSIS). ( 17901685 )
2007
41
Long-term evolution of endocrine disorders and effect of GH therapy in 35 patients with pituitary stalk interruption syndrome. ( 16260897 )
2005
42
Growth hormone deficiency associated with pituitary stalk interruption syndrome. ( 9554478 )
1998
43
Pituitary stalk interruption syndrome: a clinical-biological-genetic assessment of its pathogenesis. ( 9329385 )
1997

Variations for Pituitary Stalk Interruption Syndrome

ClinVar genetic disease variations for Pituitary Stalk Interruption Syndrome:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 GPR161 NM_001267609.1(GPR161): c.56T> A (p.Leu19Gln) single nucleotide variant Likely pathogenic rs200635937 GRCh37 Chromosome 1, 168074093: 168074093
2 GPR161 NM_001267609.1(GPR161): c.56T> A (p.Leu19Gln) single nucleotide variant Likely pathogenic rs200635937 GRCh38 Chromosome 1, 168104855: 168104855

Expression for Pituitary Stalk Interruption Syndrome

Search GEO for disease gene expression data for Pituitary Stalk Interruption Syndrome.

Pathways for Pituitary Stalk Interruption Syndrome

GO Terms for Pituitary Stalk Interruption Syndrome

Cellular components related to Pituitary Stalk Interruption Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endosome lumen GO:0031904 8.62 GH1 PRL

Biological processes related to Pituitary Stalk Interruption Syndrome according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.95 GPR161 HESX1 ROBO1 SHH SOX3 TGIF1
2 negative regulation of transcription by RNA polymerase II GO:0000122 9.93 HESX1 POU1F1 SHH SOX3 TGIF1
3 positive regulation of cell proliferation GO:0008284 9.87 GHRHR POU1F1 PRL SHH
4 mammary gland development GO:0030879 9.56 GHRHR PRL
5 positive regulation of JAK-STAT cascade GO:0046427 9.55 GH1 PRL
6 striated muscle cell differentiation GO:0051146 9.52 CDON SHH
7 embryonic morphogenesis GO:0048598 9.51 CDON SHH
8 JAK-STAT cascade involved in growth hormone signaling pathway GO:0060397 9.49 GH1 PRL
9 positive regulation of insulin-like growth factor receptor signaling pathway GO:0043568 9.46 GH1 GHRHR
10 determination of adult lifespan GO:0008340 9.43 GHRHR POU1F1
11 positive regulation of multicellular organism growth GO:0040018 9.43 GH1 GHRHR POU1F1
12 positive regulation of skeletal muscle tissue development GO:0048643 9.4 CDON SHH
13 adenohypophysis development GO:0021984 9.37 GHRHR POU1F1
14 pituitary gland development GO:0021983 9.33 HESX1 POU1F1 SOX3
15 regulation of insulin-like growth factor receptor signaling pathway GO:0043567 9.32 GHRHR POU1F1
16 somatotropin secreting cell development GO:0060133 8.96 GHRHR POU1F1
17 cell fate specification GO:0001708 8.8 CDON POU1F1 SHH

Molecular functions related to Pituitary Stalk Interruption Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 prolactin receptor binding GO:0005148 8.62 GH1 PRL

Sources for Pituitary Stalk Interruption Syndrome

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
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