CPHD4
MCID: PTT044
MIFTS: 32

Pituitary Hormone Deficiency, Combined, 4 (CPHD4)

Categories: Endocrine diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Pituitary Hormone Deficiency, Combined, 4

MalaCards integrated aliases for Pituitary Hormone Deficiency, Combined, 4:

Name: Pituitary Hormone Deficiency, Combined, 4 57 72 13 70
Short Stature-Pituitary and Cerebellar Defects-Small Sella Turcica Syndrome 20 58 29 6
Cphd4 57 20 72
Pituitary Hormone Deficiency, Combined, with or Without Cerebellar Defects 57
Pituitary Hormone Deficiency, Combined with or Without Cerebellar Defects 20
Short Stature, Pituitary and Cerebellar Defects, and Small Sella Turcica 57
Pituitary Hormone Deficiency Combined with or Without Cerebellar Defects 72
Short Stature, Pituitary and Cerebellar Defects and Small Sella Turcica 20
Short Stature Pituitary and Cerebellar Defects and Small Sella Turcica 72
Hormone Deficiency, Pituitary, Combined, Type 4 39
Pituitary Hormone Deficiency, Combined 4 20

Characteristics:

Orphanet epidemiological data:

58
short stature-pituitary and cerebellar defects-small sella turcica syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
laboratory findings are variable


HPO:

31
pituitary hormone deficiency, combined, 4:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare endocrine diseases


External Ids:

OMIM® 57 262700
OMIM Phenotypic Series 57 PS613038
MeSH 44 D007018
Orphanet 58 ORPHA85442
MedGen 41 C2678408
UMLS 70 C2678408

Summaries for Pituitary Hormone Deficiency, Combined, 4

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 85442 Definition Short stature -pituitary and cerebellar defects-small sella turcica syndrome is characterised by short stature, anterior pituitary hormone deficiency, small sella turcica, and a hypoplastic anterior hypophysis associated with pointed cerebellar tonsils. It has been described in three generations of a large French kindred. Ectopia of the posterior hypophysis was observed in some patients. The syndrome is transmitted as a dominantly inherited trait and is caused by a germline mutation within the LIM- homeobox transcription factor LHX4 gene (1q25).

MalaCards based summary : Pituitary Hormone Deficiency, Combined, 4, also known as short stature-pituitary and cerebellar defects-small sella turcica syndrome, is related to pituitary hormone deficiency, combined, 1. An important gene associated with Pituitary Hormone Deficiency, Combined, 4 is LHX4 (LIM Homeobox 4), and among its related pathways/superpathways are Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) and Fatty Acyl-CoA Biosynthesis. Affiliated tissues include pituitary, bone and thyroid, and related phenotypes are small sella turcica and hypothyroidism

UniProtKB/Swiss-Prot : 72 Pituitary hormone deficiency, combined, 4: Combined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD4 is characterized by complete or partial deficiencies of growth hormone, thyroid-stimulating hormone, luteinizing hormone, follicle stimulating hormone and adrenocorticotropic hormone. Clinical features include short stature, cerebellar defects, and small sella turcica.

More information from OMIM: 262700 PS613038

Related Diseases for Pituitary Hormone Deficiency, Combined, 4

Diseases related to Pituitary Hormone Deficiency, Combined, 4 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 pituitary hormone deficiency, combined, 1 9.1 LHX4-AS1 LHX4 ACBD6

Symptoms & Phenotypes for Pituitary Hormone Deficiency, Combined, 4

Human phenotypes related to Pituitary Hormone Deficiency, Combined, 4:

31 (show all 9)
# Description HPO Frequency HPO Source Accession
1 small sella turcica 31 very rare (1%) HP:0010538
2 hypothyroidism 31 HP:0000821
3 short stature 31 HP:0004322
4 hypoglycemia 31 HP:0001943
5 severe postnatal growth retardation 31 HP:0008850
6 adrenal insufficiency 31 HP:0000846
7 marked delay in bone age 31 HP:0003799
8 pituitary dwarfism 31 HP:0000839
9 impaired growth-hormone response to insulin stimulation test 31 HP:0031079

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Growth Height:
short stature

Skeletal:
delayed bone age

Skeletal Skull:
very small sella turcica (some)
abnormal petrous bone

Metabolic Features:
hypoglycemia

Laboratory Abnormalities:
low or absent growth hormone (gh)
low or absent luteinizing hormone (lh)
low or absent adrenocorticotropic hormone (acth)
low or absent thyroid-stimulating hormone (tsh)
low or absent follicle stimulating hormone (fsh)

Endocrine Features:
hypothyroidism (if untreated)

Clinical features from OMIM®:

262700 (Updated 20-May-2021)

Drugs & Therapeutics for Pituitary Hormone Deficiency, Combined, 4

Search Clinical Trials , NIH Clinical Center for Pituitary Hormone Deficiency, Combined, 4

Genetic Tests for Pituitary Hormone Deficiency, Combined, 4

Genetic tests related to Pituitary Hormone Deficiency, Combined, 4:

# Genetic test Affiliating Genes
1 Short Stature-Pituitary and Cerebellar Defects-Small Sella Turcica Syndrome 29 LHX4

Anatomical Context for Pituitary Hormone Deficiency, Combined, 4

MalaCards organs/tissues related to Pituitary Hormone Deficiency, Combined, 4:

40
Pituitary, Bone, Thyroid

Publications for Pituitary Hormone Deficiency, Combined, 4

Articles related to Pituitary Hormone Deficiency, Combined, 4:

# Title Authors PMID Year
1
Syndromic short stature in patients with a germline mutation in the LIM homeobox LHX4. 6 57
11567216 2001
2
Molecular and Clinical Findings in Patients with LHX4 and OTX2 Mutations. 6
23990694 2013
3
A novel dysfunctional LHX4 mutation with high phenotypical variability in patients with hypopituitarism. 6
18445675 2008
4
Three novel missense mutations within the LHX4 gene are associated with variable pituitary hormone deficiencies. 57
18073311 2008
5
A novel missense mutation (P366T) of the LHX4 gene causes severe combined pituitary hormone deficiency with pituitary hypoplasia, ectopic posterior lobe and a poorly developed sella turcica. 57
17527005 2007
6
Familial pituitary dwarfism associated with an abnormal sella turcica. 57
4305958 1969

Variations for Pituitary Hormone Deficiency, Combined, 4

ClinVar genetic disease variations for Pituitary Hormone Deficiency, Combined, 4:

6 (show top 50) (show all 59)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.569T>G (p.Leu190Arg) SNV Pathogenic 7509 rs121912643 GRCh37: 1:180240632-180240632
GRCh38: 1:180271497-180271497
2 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.1162C>A (p.Pro388Thr) SNV Pathogenic 7510 rs121912644 GRCh37: 1:180243703-180243703
GRCh38: 1:180274568-180274568
3 LHX4 NM_033343.4(LHX4):c.293dup (p.Thr99fs) Duplication Pathogenic 18444 rs587776662 GRCh37: 1:180235565-180235566
GRCh38: 1:180266430-180266431
4 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.452-2A>C SNV Pathogenic 189234 rs786204780 GRCh37: 1:180240513-180240513
GRCh38: 1:180271378-180271378
5 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.607-1G>C SNV Pathogenic 7506 rs748268631 GRCh37: 1:180240969-180240969
GRCh38: 1:180271834-180271834
6 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.628G>C (p.Ala210Pro) SNV Pathogenic 7507 rs121912641 GRCh37: 1:180240991-180240991
GRCh38: 1:180271856-180271856
7 LHX4 NM_033343.4(LHX4):c.-121T>G SNV Uncertain significance 293855 rs547988090 GRCh37: 1:180199544-180199544
GRCh38: 1:180230409-180230409
8 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.*91C>T SNV Uncertain significance 293875 rs555728017 GRCh37: 1:180243805-180243805
GRCh38: 1:180274670-180274670
9 LHX4 NM_033343.4(LHX4):c.146A>G (p.His49Arg) SNV Uncertain significance 293861 rs368995644 GRCh37: 1:180217489-180217489
GRCh38: 1:180248354-180248354
10 LHX4 NM_033343.4(LHX4):c.-172A>G SNV Uncertain significance 293853 rs376657735 GRCh37: 1:180199493-180199493
GRCh38: 1:180230358-180230358
11 LHX4 NM_033343.4(LHX4):c.83C>T (p.Pro28Leu) SNV Uncertain significance 293859 rs886045597 GRCh37: 1:180217426-180217426
GRCh38: 1:180248291-180248291
12 LHX4 NM_033343.4(LHX4):c.248+13G>A SNV Uncertain significance 293862 rs375232367 GRCh37: 1:180217604-180217604
GRCh38: 1:180248469-180248469
13 LHX4 NM_033343.4(LHX4):c.-134G>C SNV Uncertain significance 293854 rs565557892 GRCh37: 1:180199531-180199531
GRCh38: 1:180230396-180230396
14 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.998C>T (p.Thr333Met) SNV Uncertain significance 293871 rs780869144 GRCh37: 1:180243539-180243539
GRCh38: 1:180274404-180274404
15 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.*28C>A SNV Uncertain significance 293874 rs75471724 GRCh37: 1:180243742-180243742
GRCh38: 1:180274607-180274607
16 LHX4 , ACBD6 NM_033343.4(LHX4):c.*289G>A SNV Uncertain significance 293880 rs74970014 GRCh37: 1:180244003-180244003
GRCh38: 1:180274868-180274868
17 LHX4 NM_033343.4(LHX4):c.451+15C>T SNV Uncertain significance 293865 rs886045598 GRCh37: 1:180235744-180235744
GRCh38: 1:180266609-180266609
18 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.775C>G (p.Arg259Gly) SNV Uncertain significance 293868 rs747140246 GRCh37: 1:180241138-180241138
GRCh38: 1:180272003-180272003
19 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.486C>A (p.Thr162=) SNV Uncertain significance 873865 GRCh37: 1:180240549-180240549
GRCh38: 1:180271414-180271414
20 LHX4 NM_033343.4(LHX4):c.-221G>A SNV Uncertain significance 874770 GRCh37: 1:180199444-180199444
GRCh38: 1:180230309-180230309
21 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.1007G>A (p.Ser336Asn) SNV Uncertain significance 874814 GRCh37: 1:180243548-180243548
GRCh38: 1:180274413-180274413
22 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.*8T>C SNV Uncertain significance 874817 GRCh37: 1:180243722-180243722
GRCh38: 1:180274587-180274587
23 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.*17C>T SNV Uncertain significance 874818 GRCh37: 1:180243731-180243731
GRCh38: 1:180274596-180274596
24 LHX4 , ACBD6 NM_033343.4(LHX4):c.*154A>G SNV Uncertain significance 875752 GRCh37: 1:180243868-180243868
GRCh38: 1:180274733-180274733
25 LHX4 , ACBD6 NM_033343.4(LHX4):c.*221G>T SNV Uncertain significance 875753 GRCh37: 1:180243935-180243935
GRCh38: 1:180274800-180274800
26 LHX4 NM_033343.4(LHX4):c.269C>G (p.Thr90Arg) SNV Uncertain significance 876696 GRCh37: 1:180235547-180235547
GRCh38: 1:180266412-180266412
27 LHX4 NM_033343.4(LHX4):c.378G>A (p.Thr126=) SNV Uncertain significance 876697 GRCh37: 1:180235656-180235656
GRCh38: 1:180266521-180266521
28 LHX4 , ACBD6 NM_033343.4(LHX4):c.*280T>C SNV Uncertain significance 876749 GRCh37: 1:180243994-180243994
GRCh38: 1:180274859-180274859
29 LHX4 , ACBD6 NM_033343.4(LHX4):c.*460G>C SNV Uncertain significance 876750 GRCh37: 1:180244174-180244174
GRCh38: 1:180275039-180275039
30 LHX4 NM_033343.4(LHX4):c.90C>G (p.Cys30Trp) SNV Uncertain significance 931541 GRCh37: 1:180217433-180217433
GRCh38: 1:180248298-180248298
31 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.602T>C (p.Val201Ala) SNV Uncertain significance 976050 GRCh37: 1:180240665-180240665
GRCh38: 1:180271530-180271530
32 LHX4 NM_033343.4(LHX4):c.223G>A (p.Val75Ile) SNV Likely benign 876695 GRCh37: 1:180217566-180217566
GRCh38: 1:180248431-180248431
33 LHX4 NM_033343.4(LHX4):c.90C>T (p.Cys30=) SNV Likely benign 875703 GRCh37: 1:180217433-180217433
GRCh38: 1:180248298-180248298
34 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.849A>C (p.Gly283=) SNV Likely benign 873866 GRCh37: 1:180243390-180243390
GRCh38: 1:180274255-180274255
35 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.608T>G (p.Val203Gly) SNV Likely benign 801582 rs201275928 GRCh37: 1:180240971-180240971
GRCh38: 1:180271836-180271836
36 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.704G>A (p.Arg235Gln) SNV Likely benign 801583 rs765008063 GRCh37: 1:180241067-180241067
GRCh38: 1:180271932-180271932
37 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.776G>A (p.Arg259Gln) SNV Likely benign 801584 rs375216188 GRCh37: 1:180241139-180241139
GRCh38: 1:180272004-180272004
38 LHX4 NM_033343.4(LHX4):c.37G>A (p.Val13Ile) SNV Likely benign 293857 rs146664099 GRCh37: 1:180199701-180199701
GRCh38: 1:180230566-180230566
39 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.774C>T (p.Phe258=) SNV Likely benign 293867 rs565803862 GRCh37: 1:180241137-180241137
GRCh38: 1:180272002-180272002
40 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.*26C>T SNV Likely benign 293873 rs138054044 GRCh37: 1:180243740-180243740
GRCh38: 1:180274605-180274605
41 LHX4 NM_033343.4(LHX4):c.398T>C (p.Met133Thr) SNV Likely benign 293864 rs371899398 GRCh37: 1:180235676-180235676
GRCh38: 1:180266541-180266541
42 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.924T>C (p.Tyr308=) SNV Likely benign 293870 rs146655496 GRCh37: 1:180243465-180243465
GRCh38: 1:180274330-180274330
43 LHX4 NM_033343.4(LHX4):c.250C>T (p.Arg84Cys) SNV Likely benign 7508 rs121912642 GRCh37: 1:180235528-180235528
GRCh38: 1:180266393-180266393
44 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.*17C>A SNV Benign 293872 rs116482990 GRCh37: 1:180243731-180243731
GRCh38: 1:180274596-180274596
45 LHX4 , ACBD6 NM_033343.4(LHX4):c.*445G>T SNV Benign 293881 rs57069480 GRCh37: 1:180244159-180244159
GRCh38: 1:180275024-180275024
46 LHX4 NM_033343.4(LHX4):c.63T>C (p.Gly21=) SNV Benign 293858 rs75857235 GRCh37: 1:180199727-180199727
GRCh38: 1:180230592-180230592
47 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.452-5T>C SNV Benign 293866 rs2764449 GRCh37: 1:180240510-180240510
GRCh38: 1:180271375-180271375
48 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.778+14G>T SNV Benign 262224 rs3806302 GRCh37: 1:180241155-180241155
GRCh38: 1:180272020-180272020
49 LHX4-AS1 , LHX4 , ACBD6 NM_033343.4(LHX4):c.*97T>G SNV Benign 293876 rs145063714 GRCh37: 1:180243811-180243811
GRCh38: 1:180274676-180274676
50 LHX4 , ACBD6 NM_033343.4(LHX4):c.*130C>T SNV Benign 293878 rs59623342 GRCh37: 1:180243844-180243844
GRCh38: 1:180274709-180274709

UniProtKB/Swiss-Prot genetic disease variations for Pituitary Hormone Deficiency, Combined, 4:

72
# Symbol AA change Variation ID SNP ID
1 LHX4 p.Arg84Cys VAR_058715 rs121912642
2 LHX4 p.Leu190Arg VAR_058716 rs121912643
3 LHX4 p.Ala210Pro VAR_058717 rs121912641
4 LHX4 p.Pro389Thr VAR_063241 rs145433128

Expression for Pituitary Hormone Deficiency, Combined, 4

Search GEO for disease gene expression data for Pituitary Hormone Deficiency, Combined, 4.

Pathways for Pituitary Hormone Deficiency, Combined, 4

GO Terms for Pituitary Hormone Deficiency, Combined, 4

Biological processes related to Pituitary Hormone Deficiency, Combined, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 acyl-CoA metabolic process GO:0006637 8.62 LHX4-AS1 ACBD6

Molecular functions related to Pituitary Hormone Deficiency, Combined, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid binding GO:0008289 8.96 LHX4-AS1 ACBD6
2 fatty-acyl-CoA binding GO:0000062 8.62 LHX4-AS1 ACBD6

Sources for Pituitary Hormone Deficiency, Combined, 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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