PSIS
MCID: PTT041
MIFTS: 47

Pituitary Stalk Interruption Syndrome (PSIS)

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 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 growth 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 Testosterone and tannic acid have been mentioned in the context of this disorder. Affiliated tissues include pituitary, testis and hypothalamus, and related phenotypes are hypothyroidism and intellectual disability

Wikipedia : 76 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 79)
# Related Disease Score Top Affiliating Genes
1 growth hormone deficiency 30.2 GH1 GHRHR HESX1 SOX3
2 holoprosencephaly 30.1 CDON SHH TGIF1
3 combined pituitary hormone deficiency 30.0 HESX1 LHX4 POU1F1
4 pituitary hormone deficiency, combined, 2 29.2 GH1 HESX1 LHX4 POU1F1 PRL SOX3
5 hypopituitarism 29.2 GH1 HESX1 LHX4 POU1F1 PRL SOX3
6 pituitary hypoplasia 29.2 GHRHR HESX1 LHX4 POU1F1 PRL SOX3
7 central congenital hypothyroidism 11.4
8 hypogonadotropic hypogonadism 7 with or without anosmia 10.1 PROKR2 WDR11
9 isolated growth hormone deficiency type iii 10.1 HESX1 SOX3
10 normosmic congenital hypogonadotropic hypogonadism 10.1 PROKR2 WDR11
11 pneumonia 10.1
12 isolated growth hormone deficiency, type ib 10.1 GH1 GHRHR
13 insulin-like growth factor i 10.1
14 cholestasis 10.1
15 fibrous dysplasia/mccune-albright syndrome 10.1 GH1 PRL
16 adenohypophysitis 10.0 GH1 PRL
17 pseudohypoparathyroidism, type ia 10.0 GH1 PRL
18 hypothalamic disease 10.0 GH1 PRL
19 platelet membrane fluidity 10.0
20 alpha-thalassemia 10.0
21 thalassemia 10.0
22 gigantism 10.0 GH1 PRL
23 holoprosencephaly 4 10.0 SHH TGIF1
24 empty sella syndrome 10.0 GH1 PRL
25 hyperpituitarism 10.0 GH1 PRL
26 kallmann syndrome 10.0 HESX1 PROKR2 WDR11
27 tsh producing pituitary tumor 10.0 GH1 PRL
28 growth hormone secreting pituitary adenoma 10.0 GHRHR PRL
29 brachydactyly, type a1 10.0 CDON SHH
30 functioning pituitary adenoma 10.0 GH1 PRL
31 axenfeld-rieger syndrome, type 1 10.0 HESX1 SHH
32 tetrahydrobiopterin deficiency 10.0 GH1 PRL
33 septopreoptic holoprosencephaly 10.0 CDON SHH TGIF1
34 midline interhemispheric variant of holoprosencephaly 10.0 CDON SHH TGIF1
35 alobar holoprosencephaly 10.0 CDON SHH TGIF1
36 pituitary adenoma 1, multiple types 10.0 GH1 PRL
37 lobar holoprosencephaly 10.0 CDON SHH TGIF1
38 microform holoprosencephaly 10.0 CDON SHH TGIF1
39 semilobar holoprosencephaly 10.0 CDON SHH TGIF1
40 hypothyroidism due to deficient transcription factors involved in pituitary development or function 10.0 HESX1 LHX4 POU1F1
41 gonadal disease 9.9 GH1 PRL PROKR2
42 combined pituitary hormone deficiencies, genetic forms 9.9 HESX1 LHX4 POU1F1
43 chromophobe adenoma 9.9 GH1 PRL
44 solitary median maxillary central incisor 9.9
45 suprabulbar paresis, congenital 9.9
46 polymicrogyria, bilateral perisylvian, x-linked 9.9
47 heterotaxy, visceral, 1, x-linked 9.9
48 microphthalmia 9.9
49 turner syndrome 9.9
50 heterotaxy 9.9

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

MGI Mouse Phenotypes related to Pituitary Stalk Interruption Syndrome:

46 (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
Testosterone Approved, Investigational Not Applicable 58-22-0 6013
2 tannic acid Approved Not Applicable
3
Benzocaine Approved, Investigational Not Applicable 94-09-7, 1994-09-7 2337
4 Hormones, Hormone Substitutes, and Hormone Antagonists Not Applicable
5 Prolactin Release-Inhibiting Factors Not Applicable
6 Hormones Not Applicable
7 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, Lung

Publications for Pituitary Stalk Interruption Syndrome

Articles related to Pituitary Stalk Interruption Syndrome:

(show top 50) (show all 51)
# 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
High-resolution heavily T2-weighted magnetic resonance imaging for evaluation of the pituitary stalk in children with ectopic neurohypophysis. ( 28255689 )
2017
12
Extra-pituitary Cerebral Anomalies in Pediatric Patients of Ectopic Neurohypophysis: An Uncommon Association. ( 28584686 )
2017
13
Pituitary stalk interruption syndrome: cause, clinical manifestations, diagnosis, and management. ( 27386973 )
2016
14
Pituitary Stalk Interruption Syndrome Presenting With Growth Retardation. ( 27238408 )
2016
15
Growth Hormone Therapy Benefits Pituitary Stalk Interruption Syndrome Patients with Short Stature: A Retrospective Study of 75 Han Chinese. ( 27190512 )
2016
16
Pituitary stalk interruption syndrome: From clinical findings to pathogenesis. ( 27917547 )
2016
17
A case of pituitary stalk interruption syndrome with intermittent seizures as the first presentation. ( 28326739 )
2016
18
Clinical Features of Pituitary Stalk Interruption Syndrome in 114 Cases. ( 27825409 )
2016
19
Cholestasis Reveals Severe Cortisol Deficiency in Neonatal Pituitary Stalk Interruption Syndrome. ( 26829045 )
2016
20
Correlation between Pituitary Stalk Interruption Syndrome and Prokineticin Receptor 2 and Prokineticin 2 Mutations. ( 26956854 )
2016
21
A nonsense mutation in the hedgehog receptor CDON associated with pituitary stalk interruption syndrome. ( 26529631 )
2015
22
Pituitary Stalk Interruption Syndrome from Infancy to Adulthood: Clinical, Hormonal, and Radiological Assessment According to the Initial Presentation. ( 26562670 )
2015
23
Pituitary stalk interruption syndrome: Case report of three cases with review of literature. ( 25250085 )
2014
24
Whole exome sequencing identifies homozygous GPR161 mutation in a family with pituitary stalk interruption syndrome. ( 25322266 )
2014
25
Pituitary stalk interruption syndrome presenting as short stature: a case report. ( 25524465 )
2014
26
MRI findings of coexistence of ectopic neurohypophysis, corpus callosum dysgenesis, and periventricular neuronal heterotopia. ( 24987569 )
2014
27
Pituitary stalk interruption syndrome in Chinese people: clinical characteristic analysis of 55 cases. ( 23341953 )
2013
28
Pituitary stalk interruption syndrome and isolated pituitary hypoplasia may be caused by mutations in holoprosencephaly-related genes. ( 23476075 )
2013
29
Pituitary stalk interruption syndrome in 59 children: the value of MRI in assessment of pituitary functions. ( 24257915 )
2013
30
Pituitary stalk interruption syndrome in 53 postpubertal patients: factors influencing the heterogeneity of its presentation. ( 23308160 )
2013
31
Pituitary stalk interruption syndrome in 58 Chinese patients: clinical features and genetic analysis. ( 23199197 )
2013
32
Pituitary stalk interruption syndrome. ( 24617191 )
2013
33
17q21.31 microdeletion in a patient with pituitary stalk interruption syndrome. ( 21397059 )
2011
34
Magnetic resonance image of sellar region in pituitary stalk interruption syndrome in children and adolescents. ( 21375930 )
2011
35
Pituitary stalk interruption syndrome in 83 patients: novel HESX1 mutation and severe hormonal prognosis in malformative forms. ( 21270112 )
2011
36
Pituitary stalk interruption syndrome: diagnostic delay and sensitivity of the auxological criteria of the growth hormone research society. ( 21298012 )
2011
37
Renal anomalies associated with ectopic neurohypophysis. ( 21750632 )
2011
38
Oral manifestation associated with multiple pituitary hormone deficiency and ectopic neurohypophysis. ( 22046701 )
2011
39
Pituitary stalk interruption syndrome: the role of MRI and review of the literature. ( 24148682 )
2010
40
The pituitary stalk interruption syndrome: endocrine features and benefits of growth hormone therapy. ( 20044069 )
2010
41
Diagnosis of growth hormone (GH) deficiency: comparison of pituitary stalk interruption syndrome and transient GH deficiency. ( 19419564 )
2009
42
Gonadotrophic status in adolescents with pituitary stalk interruption syndrome. ( 18088398 )
2008
43
Factors influencing the growth hormone peak and plasma insulin-like growth factor I in young adults with pituitary stalk interruption syndrome. ( 18620575 )
2008
44
Pituitary stalk interruption syndrome (PSIS). ( 17901685 )
2007
45
Delayed puberty due to pituitary stalk dysgenesis and ectopic neurohypophysis. ( 16646569 )
2006
46
Long-term evolution of endocrine disorders and effect of GH therapy in 35 patients with pituitary stalk interruption syndrome. ( 16260897 )
2005
47
Do all patients with childhood-onset growth hormone deficiency (GHD) and ectopic neurohypophysis have persistent GHD in adulthood? ( 15546901 )
2005
48
Growth hormone deficiency with ectopic neurohypophysis: anatomical variations and relationship between the visibility of the pituitary stalk asserted by magnetic resonance imaging and anterior pituitary function. ( 10404812 )
1999
49
Growth hormone deficiency associated with pituitary stalk interruption syndrome. ( 9554478 )
1998
50
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

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

# Super pathways Score Top Affiliating Genes
1 11.49 CDON HESX1 SHH
2
Show member pathways
11.24 CDON GPR161 SHH
3
Show member pathways
10.93 GH1 PRL
4
Show member pathways
10.73 CDON SHH
5 9.58 SHH TGIF1

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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9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
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62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
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71 TGDB
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74 UMLS via Orphanet
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