MCID: PTT041
MIFTS: 49

Pituitary Stalk Interruption Syndrome

Categories: Endocrine diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Pituitary Stalk Interruption Syndrome

MalaCards integrated aliases for Pituitary Stalk Interruption Syndrome:

Name: Pituitary Stalk Interruption Syndrome 54 60 6 74
Ectopic Neurohypophysis 54 60
Psis 54 60

Characteristics:

Orphanet epidemiological data:

60
pituitary stalk interruption syndrome
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Age of onset: Childhood; Age of death: early childhood;

HPO:

33
pituitary stalk interruption syndrome:
Clinical modifier death in infancy


Classifications:

Orphanet: 60  
Rare endocrine diseases


Summaries for Pituitary Stalk Interruption Syndrome

NIH Rare Diseases : 54 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 growth hormone deficiency. 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 neutrophil, and related phenotypes are ectopic posterior pituitary and failure to thrive

Wikipedia : 77 Pituitary stalk interruption syndrome (PSIS) is a congenital disorder characterised by the triad of an... more...

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 94)
# Related Disease Score Top Affiliating Genes
1 combined pituitary hormone deficiency 30.3 HESX1 LHX4 POU1F1
2 growth hormone deficiency 30.0 GH1 GHRHR HESX1 SOX3
3 holoprosencephaly 29.7 CDON SHH TGIF1
4 pituitary hypoplasia 29.0 GHRHR HESX1 LHX4 POU1F1 PRL SOX3
5 pituitary hormone deficiency, combined, 2 29.0 GH1 HESX1 LHX4 POU1F1 PRL SOX3
6 hypopituitarism 29.0 GH1 HESX1 LHX4 POU1F1 PRL SOX3
7 central congenital hypothyroidism 11.4
8 pneumonia 10.3
9 normosmic congenital hypogonadotropic hypogonadism 10.2 PROKR2 WDR11
10 isolated growth hormone deficiency, type ib 10.1 GH1 GHRHR
11 isolated growth hormone deficiency type iii 10.1 HESX1 SOX3
12 hypothyroidism due to deficient transcription factors involved in pituitary development or function 10.1 HESX1 LHX4 POU1F1
13 combined pituitary hormone deficiencies, genetic forms 10.1 HESX1 LHX4 POU1F1
14 cystic fibrosis 10.1
15 fibrous dysplasia/mccune-albright syndrome 10.1 GH1 PRL
16 pituitary hormone deficiency, combined, 1 10.1 HESX1 LHX4 POU1F1
17 adenohypophysitis 10.1 GH1 PRL
18 pseudohypoparathyroidism, type ia 10.1 GH1 PRL
19 hypothalamic disease 10.1 GH1 PRL
20 gigantism 10.1 GH1 PRL
21 growth hormone secreting pituitary adenoma 10.1 GHRHR PRL
22 empty sella syndrome 10.1 GH1 PRL
23 insulin-like growth factor i 10.1
24 brittle bone disorder 10.1
25 cholestasis 10.1
26 col1a1/2-related osteogenesis imperfecta 10.1
27 seizure disorder 10.1
28 hyperpituitarism 10.1 GH1 PRL
29 tsh producing pituitary tumor 10.1 GH1 PRL
30 kallmann syndrome 10.0 HESX1 PROKR2 WDR11
31 functioning pituitary adenoma 10.0 GH1 PRL
32 neutrophil migration 10.0
33 platelet membrane fluidity 10.0
34 lung cancer 10.0
35 alpha-thalassemia 10.0
36 human immunodeficiency virus type 1 10.0
37 deafness-infertility syndrome 10.0
38 thalassemia 10.0
39 tetrahydrobiopterin deficiency 10.0 GH1 PRL
40 pituitary adenoma 1, multiple types 10.0 GH1 PRL
41 solitary median maxillary central incisor 10.0
42 suprabulbar paresis, congenital 10.0
43 polymicrogyria, bilateral perisylvian, x-linked 10.0
44 heterotaxy, visceral, 1, x-linked 10.0
45 microphthalmia 10.0
46 turner syndrome 10.0
47 heterotaxy 10.0
48 polymicrogyria 10.0
49 gonadal disease 10.0 GH1 PRL PROKR2
50 chromophobe adenoma 10.0 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:

60 33 (show all 17)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ectopic posterior pituitary 60 33 obligate (100%) Obligate (100%) HP:0011755
2 failure to thrive 60 33 hallmark (90%) Very frequent (99-80%) HP:0001508
3 short stature 60 33 hallmark (90%) Very frequent (99-80%) HP:0004322
4 hypothyroidism 60 33 frequent (33%) Frequent (79-30%) HP:0000821
5 delayed puberty 60 33 frequent (33%) Frequent (79-30%) HP:0000823
6 hypoglycemia 60 33 frequent (33%) Frequent (79-30%) HP:0001943
7 hypoplasia of penis 60 33 frequent (33%) Frequent (79-30%) HP:0008736
8 intellectual disability 60 33 occasional (7.5%) Occasional (29-5%) HP:0001249
9 seizures 60 33 occasional (7.5%) Occasional (29-5%) HP:0001250
10 global developmental delay 60 33 occasional (7.5%) Occasional (29-5%) HP:0001263
11 cryptorchidism 60 33 occasional (7.5%) Occasional (29-5%) HP:0000028
12 primary amenorrhea 60 33 occasional (7.5%) Occasional (29-5%) HP:0000786
13 diabetes insipidus 60 33 occasional (7.5%) Occasional (29-5%) HP:0000873
14 adrenal hypoplasia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000835
15 septo-optic dysplasia 60 33 occasional (7.5%) Occasional (29-5%) HP:0100842
16 death in infancy 60 Occasional (29-5%)
17 abnormality of the hypothalamus-pituitary axis 60 Very frequent (99-80%)

MGI Mouse Phenotypes related to Pituitary Stalk Interruption Syndrome:

47 (show all 15)
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.22 CDON GHRHR GPR161 HESX1 POU1F1 PROKR2
2 behavior/neurological MP:0005386 10.2 CDON GHRHR GPR161 PRL PROKR2 ROBO1
3 endocrine/exocrine gland MP:0005379 10.19 GHRHR HESX1 LHX4 POU1F1 PRL PROKR2
4 craniofacial MP:0005382 10.18 CDON GPR161 HESX1 POU1F1 ROBO1 SHH
5 nervous system MP:0003631 10.18 CDON GHRHR GPR161 HESX1 LHX4 POU1F1
6 cellular MP:0005384 10.14 CDON POU1F1 PROKR2 ROBO1 SHH SOX3
7 mortality/aging MP:0010768 10.14 CDON GPR161 HESX1 LHX4 POU1F1 PROKR2
8 homeostasis/metabolism MP:0005376 10.11 GHRHR LHX4 POU1F1 PRL PROKR2 ROBO1
9 embryo MP:0005380 10.05 CDON GPR161 HESX1 SHH SOX3 TGIF1
10 reproductive system MP:0005389 9.97 GHRHR POU1F1 PRL PROKR2 ROBO1 SHH
11 limbs/digits/tail MP:0005371 9.91 CDON GHRHR GPR161 SHH TGIF1 WDR11
12 respiratory system MP:0005388 9.8 CDON HESX1 LHX4 ROBO1 SHH TGIF1
13 skeleton MP:0005390 9.76 CDON GHRHR POU1F1 ROBO1 SHH SOX3
14 taste/olfaction MP:0005394 9.26 HESX1 SHH TGIF1 WDR11
15 vision/eye MP:0005391 9.1 CDON GPR161 HESX1 SHH TGIF1 WDR11

Drugs & Therapeutics for Pituitary Stalk Interruption Syndrome

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

(show all 7)
# 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, Experimental, Investigational Not Applicable 58-22-0, 481-30-1 10204 6013
3
tannic acid Approved Not Applicable 1401-55-4
4 Hormone Antagonists Not Applicable
5 Hormones Not Applicable
6 Prolactin Release-Inhibiting Factors Not Applicable
7 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:

42
Pituitary, Testis, Neutrophil, Hypothalamus, Bone

Publications for Pituitary Stalk Interruption Syndrome

Articles related to Pituitary Stalk Interruption Syndrome:

(show top 50) (show all 61)
# Title Authors Year
1
Osteogenesis Imperfecta Due to Combined Heterozygous Mutations in Both COL1A1 and COL1A2, Coexisting With Pituitary Stalk Interruption Syndrome. ( 30984112 )
2019
2
Pituitary stalk interruption syndrome. ( 30988112 )
2019
3
Vitamin D in children with growth hormone deficiency due to pituitary stalk interruption syndrome. ( 29368588 )
2018
4
Persistent craniopharyngeal canal, bilateral microphthalmia with colobomatous cysts, ectopic adenohypophysis with Rathke cleft cyst, and ectopic neurohypophysis: case report and review of the literature. ( 29445918 )
2018
5
Clues for Polygenic Inheritance of Pituitary Stalk Interruption Syndrome From Exome Sequencing in 20 Patients. ( 29165578 )
2018
6
Thyrotrophic status in patients with pituitary stalk interruption syndrome. ( 29480822 )
2018
7
Pituitary stalk interruption syndrome presenting in a euthyroid adult with short stature. ( 29904499 )
2018
8
Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome. ( 28443260 )
2017
9
The Missing Link: A Case of Absent Pituitary Infundibulum and Ectopic Neurohypophysis in a Pediatric Patient with Heterotaxy Syndrome. ( 29299107 )
2017
10
Multi-genic pattern found in rare type of hypopituitarism: a whole-exome sequencing study of Han Chinese with pituitary stalk interruption syndrome. ( 28707430 )
2017
11
Pituitary Stalk Interruption Syndrome: From Clinical Findings to Pathogenesis. ( 27917547 )
2017
12
Pituitary stalk interruption syndrome: a rare and severe cause of pituitary deficiency Laboratory diagnosis of a newborn case. ( 28251898 )
2017
13
Mutations in the Human ROBO1 Gene in Pituitary Stalk Interruption Syndrome. ( 28402530 )
2017
14
Digenic Inheritance of PROKR2 and WDR11 Mutations in Pituitary Stalk Interruption Syndrome. ( 28453858 )
2017
15
Delayed diagnosis of pituitary stalk interruption syndrome with severe recurrent hyponatremia caused by adrenal insufficiency. ( 29025209 )
2017
16
High-resolution heavily T2-weighted magnetic resonance imaging for evaluation of the pituitary stalk in children with ectopic neurohypophysis. ( 28255689 )
2017
17
Extra-pituitary Cerebral Anomalies in Pediatric Patients of Ectopic Neurohypophysis: An Uncommon Association. ( 28584686 )
2017
18
Cholestasis Reveals Severe Cortisol Deficiency in Neonatal Pituitary Stalk Interruption Syndrome. ( 26829045 )
2016
19
A Nonsense Mutation in the Hedgehog Receptor CDON Associated With Pituitary Stalk Interruption Syndrome. ( 26529631 )
2016
20
Correlation between Pituitary Stalk Interruption Syndrome and Prokineticin Receptor 2 and Prokineticin 2 Mutations. ( 26956854 )
2016
21
Growth Hormone Therapy Benefits Pituitary Stalk Interruption Syndrome Patients with Short Stature: A Retrospective Study of 75 Han Chinese. ( 27190512 )
2016
22
Pituitary Stalk Interruption Syndrome Presenting With Growth Retardation. ( 27238408 )
2016
23
Pituitary stalk interruption syndrome: cause, clinical manifestations, diagnosis, and management. ( 27386973 )
2016
24
Clinical Features of Pituitary Stalk Interruption Syndrome in 114 Cases. ( 27825409 )
2016
25
A case of pituitary stalk interruption syndrome with intermittent seizures as the first presentation. ( 28326739 )
2016
26
Whole-exome sequencing identifies homozygous GPR161 mutation in a family with pituitary stalk interruption syndrome. ( 25322266 )
2015
27
Pituitary Stalk Interruption Syndrome from Infancy to Adulthood: Clinical, Hormonal, and Radiological Assessment According to the Initial Presentation. ( 26562670 )
2015
28
Multiple Pituitary Hormone Deficiency, Empty Sella and Ectopic Neurohypophysis in Turner Syndrome. ( 26519720 )
2015
29
Pituitary stalk interruption syndrome in 59 children: the value of MRI in assessment of pituitary functions. ( 24257915 )
2014
30
Pituitary stalk interruption syndrome: Case report of three cases with review of literature. ( 25250085 )
2014
31
Pituitary stalk interruption syndrome presenting as short stature: a case report. ( 25524465 )
2014
32
MRI findings of coexistence of ectopic neurohypophysis, corpus callosum dysgenesis, and periventricular neuronal heterotopia. ( 24987569 )
2014
33
Solitary median maxillary central incisor, a clinical predictor of hypoplastic anterior pituitary, ectopic neurohypophysis and growth hormone deficiency. ( 23729612 )
2013
34
Pituitary stalk interruption syndrome and isolated pituitary hypoplasia may be caused by mutations in holoprosencephaly-related genes. ( 23476075 )
2013
35
Pituitary stalk interruption syndrome in 58 Chinese patients: clinical features and genetic analysis. ( 23199197 )
2013
36
Pituitary stalk interruption syndrome in 53 postpubertal patients: factors influencing the heterogeneity of its presentation. ( 23308160 )
2013
37
Pituitary stalk interruption syndrome in Chinese people: clinical characteristic analysis of 55 cases. ( 23341953 )
2013
38
Pituitary stalk interruption syndrome. ( 24617191 )
2013
39
Rathke's cyst with ectopic neurohypophysis presenting as severe short stature with delayed puberty. ( 23565402 )
2012
40
Pituitary stalk interruption syndrome in 83 patients: novel HESX1 mutation and severe hormonal prognosis in malformative forms. ( 21270112 )
2011
41
Pituitary stalk interruption syndrome: diagnostic delay and sensitivity of the auxological criteria of the growth hormone research society. ( 21298012 )
2011
42
Magnetic resonance image of sellar region in pituitary stalk interruption syndrome in children and adolescents. ( 21375930 )
2011
43
17q21.31 microdeletion in a patient with pituitary stalk interruption syndrome. ( 21397059 )
2011
44
Bilateral perisylvian polymicrogyria with cerebellar dysplasia and ectopic neurohypophysis. ( 21273507 )
2011
45
Renal anomalies associated with ectopic neurohypophysis. ( 21750632 )
2011
46
Oral manifestation associated with multiple pituitary hormone deficiency and ectopic neurohypophysis. ( 22046701 )
2011
47
The pituitary stalk interruption syndrome: endocrine features and benefits of growth hormone therapy. ( 20044069 )
2010
48
Pituitary stalk interruption syndrome: the role of MRI and review of the literature. ( 24148682 )
2010
49
Diagnosis of growth hormone (GH) deficiency: comparison of pituitary stalk interruption syndrome and transient GH deficiency. ( 19419564 )
2009
50
Factors influencing the growth hormone peak and plasma insulin-like growth factor I in young adults with pituitary stalk interruption syndrome. ( 18620575 )
2008

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 9.91 GPR161 HESX1 ROBO1 SHH SOX3 TGIF1
2 positive regulation of cell proliferation GO:0008284 9.87 GHRHR POU1F1 PRL SHH
3 mammary gland development GO:0030879 9.56 GHRHR PRL
4 positive regulation of JAK-STAT cascade GO:0046427 9.54 GH1 PRL
5 embryonic morphogenesis GO:0048598 9.52 CDON SHH
6 determination of adult lifespan GO:0008340 9.51 GHRHR POU1F1
7 striated muscle cell differentiation GO:0051146 9.49 CDON SHH
8 JAK-STAT cascade involved in growth hormone signaling pathway GO:0060397 9.48 GH1 PRL
9 positive regulation of insulin-like growth factor receptor signaling pathway GO:0043568 9.46 GH1 GHRHR
10 positive regulation of multicellular organism growth GO:0040018 9.43 GH1 GHRHR POU1F1
11 adenohypophysis development GO:0021984 9.4 GHRHR POU1F1
12 positive regulation of skeletal muscle tissue development GO:0048643 9.37 CDON SHH
13 regulation of insulin-like growth factor receptor signaling pathway GO:0043567 9.32 GHRHR POU1F1
14 somatotropin secreting cell development GO:0060133 9.16 GHRHR POU1F1
15 pituitary gland development GO:0021983 9.13 HESX1 POU1F1 SOX3
16 cell fate specification GO:0001708 8.8 CDON POU1F1 SHH
17 regulation of transcription, DNA-templated GO:0006355 10.02 HESX1 LHX4 POU1F1 SHH SOX3 TGIF1

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

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10 dbSNP
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18 ExPASy
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59 OMIM via Orphanet
63 PubMed
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70 SNOMED-CT via HPO
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75 UMLS via Orphanet
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