CPHD4
MCID: PTT044
MIFTS: 27

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 56 73 13 71
Short Stature-Pituitary and Cerebellar Defects-Small Sella Turcica Syndrome 52 58 29 6
Cphd4 56 52 73
Pituitary Hormone Deficiency, Combined, with or Without Cerebellar Defects 56
Pituitary Hormone Deficiency, Combined with or Without Cerebellar Defects 52
Short Stature, Pituitary and Cerebellar Defects, and Small Sella Turcica 56
Pituitary Hormone Deficiency Combined with or Without Cerebellar Defects 73
Short Stature, Pituitary and Cerebellar Defects and Small Sella Turcica 52
Short Stature Pituitary and Cerebellar Defects and Small Sella Turcica 73
Hormone Deficiency, Pituitary, Combined, Type 4 39
Pituitary Hormone Deficiency, Combined 4 52

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:

56
Inheritance:
autosomal dominant

Miscellaneous:
laboratory findings are variable


HPO:

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


Classifications:

Orphanet: 58  
Rare endocrine diseases


External Ids:

OMIM 56 262700
OMIM Phenotypic Series 56 PS613038
MeSH 43 D007018
Orphanet 58 ORPHA85442
MedGen 41 C2678408
UMLS 71 C2678408

Summaries for Pituitary Hormone Deficiency, Combined, 4

NIH Rare Diseases : 52 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). Visit the Orphanet disease page for more resources.

MalaCards based summary : Pituitary Hormone Deficiency, Combined, 4, is also known as short stature-pituitary and cerebellar defects-small sella turcica syndrome. An important gene associated with Pituitary Hormone Deficiency, Combined, 4 is LHX4 (LIM Homeobox 4). Affiliated tissues include pituitary, thyroid and tonsil, and related phenotypes are small sella turcica and hypothyroidism

UniProtKB/Swiss-Prot : 73 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

Symptoms & Phenotypes for Pituitary Hormone Deficiency, Combined, 4

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

31 (show all 7)
# Description HPO Frequency HPO Source Accession
1 small sella turcica 31 occasional (7.5%) HP:0010538
2 hypothyroidism 31 HP:0000821
3 hypoglycemia 31 HP:0001943
4 severe postnatal growth retardation 31 HP:0008850
5 adrenal insufficiency 31 HP:0000846
6 marked delay in bone age 31 HP:0003799
7 pituitary dwarfism 31 HP:0000839

Symptoms via clinical synopsis from OMIM:

56
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

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, Thyroid, Tonsil, Bone

Publications for Pituitary Hormone Deficiency, Combined, 4

Articles related to Pituitary Hormone Deficiency, Combined, 4:

# Title Authors PMID Year
1
Three novel missense mutations within the LHX4 gene are associated with variable pituitary hormone deficiencies. 6 56
18073311 2008
2
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. 6 56
17527005 2007
3
Syndromic short stature in patients with a germline mutation in the LIM homeobox LHX4. 56 6
11567216 2001
4
A novel dysfunctional LHX4 mutation with high phenotypical variability in patients with hypopituitarism. 6
18445675 2008
5
"Hot spot" in the PROP1 gene responsible for combined pituitary hormone deficiency. 6
10323394 1999
6
The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency. 6
9745452 1998
7
Familial pituitary dwarfism associated with an abnormal sella turcica. 56
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 57) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 LHX4 NM_033343.4(LHX4):c.607-1G>CSNV Pathogenic 7506 rs748268631 1:180240969-180240969 1:180271834-180271834
2 LHX4 NM_033343.4(LHX4):c.628G>C (p.Ala210Pro)SNV Pathogenic 7507 rs121912641 1:180240991-180240991 1:180271856-180271856
3 LHX4 NM_033343.4(LHX4):c.569T>G (p.Leu190Arg)SNV Pathogenic 7509 rs121912643 1:180240632-180240632 1:180271497-180271497
4 LHX4 NM_033343.4(LHX4):c.1162C>A (p.Pro388Thr)SNV Pathogenic 7510 rs121912644 1:180243703-180243703 1:180274568-180274568
5 LHX4 NM_033343.4(LHX4):c.293dup (p.Thr99fs)duplication Pathogenic 18444 rs587776662 1:180235565-180235566 1:180266430-180266431
6 LHX4 NM_033343.4(LHX4):c.452-2A>CSNV Pathogenic 189234 rs786204780 1:180240513-180240513 1:180271378-180271378
7 LHX4 NM_033343.4(LHX4):c.37G>A (p.Val13Ile)SNV Conflicting interpretations of pathogenicity 293857 rs146664099 1:180199701-180199701 1:180230566-180230566
8 LHX4 NM_033343.4(LHX4):c.146A>G (p.His49Arg)SNV Uncertain significance 293861 rs368995644 1:180217489-180217489 1:180248354-180248354
9 LHX4 NM_033343.4(LHX4):c.998C>T (p.Thr333Met)SNV Uncertain significance 293871 rs780869144 1:180243539-180243539 1:180274404-180274404
10 LHX4 NM_033343.4(LHX4):c.775C>G (p.Arg259Gly)SNV Uncertain significance 293868 rs747140246 1:180241138-180241138 1:180272003-180272003
11 LHX4 NM_033343.4(LHX4):c.*289G>ASNV Uncertain significance 293880 rs74970014 1:180244003-180244003 1:180274868-180274868
12 LHX4 NM_033343.4(LHX4):c.-172A>GSNV Uncertain significance 293853 rs376657735 1:180199493-180199493 1:180230358-180230358
13 LHX4 NM_033343.4(LHX4):c.-121T>GSNV Uncertain significance 293855 rs547988090 1:180199544-180199544 1:180230409-180230409
14 LHX4 NM_033343.4(LHX4):c.83C>T (p.Pro28Leu)SNV Uncertain significance 293859 rs886045597 1:180217426-180217426 1:180248291-180248291
15 LHX4 NM_033343.4(LHX4):c.*28C>ASNV Uncertain significance 293874 rs75471724 1:180243742-180243742 1:180274607-180274607
16 LHX4 NM_033343.4(LHX4):c.248+13G>ASNV Uncertain significance 293862 rs375232367 1:180217604-180217604 1:180248469-180248469
17 LHX4 NM_033343.4(LHX4):c.451+15C>TSNV Uncertain significance 293865 rs886045598 1:180235744-180235744 1:180266609-180266609
18 LHX4 NM_033343.4(LHX4):c.*91C>TSNV Uncertain significance 293875 rs555728017 1:180243805-180243805 1:180274670-180274670
19 LHX4 NM_033343.4(LHX4):c.-134G>CSNV Uncertain significance 293854 rs565557892 1:180199531-180199531 1:180230396-180230396
20 LHX4 NM_033343.4(LHX4):c.1007G>A (p.Ser336Asn)SNV Uncertain significance 874814 1:180243548-180243548 1:180274413-180274413
21 LHX4 NM_033343.4(LHX4):c.*8T>CSNV Uncertain significance 874817 1:180243722-180243722 1:180274587-180274587
22 LHX4 NM_033343.4(LHX4):c.*17C>TSNV Uncertain significance 874818 1:180243731-180243731 1:180274596-180274596
23 LHX4 NM_033343.4(LHX4):c.*154A>GSNV Uncertain significance 875752 1:180243868-180243868 1:180274733-180274733
24 LHX4 NM_033343.4(LHX4):c.*221G>TSNV Uncertain significance 875753 1:180243935-180243935 1:180274800-180274800
25 LHX4 NM_033343.4(LHX4):c.*280T>CSNV Uncertain significance 876749 1:180243994-180243994 1:180274859-180274859
26 LHX4 NM_033343.4(LHX4):c.*460G>CSNV Uncertain significance 876750 1:180244174-180244174 1:180275039-180275039
27 LHX4 NM_033343.4(LHX4):c.-221G>ASNV Uncertain significance 874770 1:180199444-180199444 1:180230309-180230309
28 LHX4 NM_033343.4(LHX4):c.269C>G (p.Thr90Arg)SNV Uncertain significance 876696 1:180235547-180235547 1:180266412-180266412
29 LHX4 NM_033343.4(LHX4):c.378G>A (p.Thr126=)SNV Uncertain significance 876697 1:180235656-180235656 1:180266521-180266521
30 LHX4 NM_033343.4(LHX4):c.486C>A (p.Thr162=)SNV Uncertain significance 873865 1:180240549-180240549 1:180271414-180271414
31 LHX4 NM_033343.4(LHX4):c.849A>C (p.Gly283=)SNV Likely benign 873866 1:180243390-180243390 1:180274255-180274255
32 LHX4 NM_033343.4(LHX4):c.90C>T (p.Cys30=)SNV Likely benign 875703 1:180217433-180217433 1:180248298-180248298
33 LHX4 NM_033343.4(LHX4):c.223G>A (p.Val75Ile)SNV Likely benign 876695 1:180217566-180217566 1:180248431-180248431
34 LHX4 NM_033343.4(LHX4):c.608T>G (p.Val203Gly)SNV Likely benign 801582 1:180240971-180240971 1:180271836-180271836
35 LHX4 NM_033343.4(LHX4):c.704G>A (p.Arg235Gln)SNV Likely benign 801583 1:180241067-180241067 1:180271932-180271932
36 LHX4 NM_033343.4(LHX4):c.776G>A (p.Arg259Gln)SNV Likely benign 801584 1:180241139-180241139 1:180272004-180272004
37 LHX4 NM_033343.4(LHX4):c.250C>T (p.Arg84Cys)SNV Likely benign 7508 rs121912642 1:180235528-180235528 1:180266393-180266393
38 LHX4 NM_033343.4(LHX4):c.*26C>TSNV Likely benign 293873 rs138054044 1:180243740-180243740 1:180274605-180274605
39 LHX4 NM_033343.4(LHX4):c.774C>T (p.Phe258=)SNV Likely benign 293867 rs565803862 1:180241137-180241137 1:180272002-180272002
40 LHX4 NM_033343.4(LHX4):c.398T>C (p.Met133Thr)SNV Likely benign 293864 rs371899398 1:180235676-180235676 1:180266541-180266541
41 LHX4 NM_033343.4(LHX4):c.924T>C (p.Tyr308=)SNV Benign/Likely benign 293870 rs146655496 1:180243465-180243465 1:180274330-180274330
42 LHX4 NM_033343.4(LHX4):c.*119T>CSNV Benign 293877 rs180725260 1:180243833-180243833 1:180274698-180274698
43 LHX4 NM_033343.4(LHX4):c.63T>C (p.Gly21=)SNV Benign 293858 rs75857235 1:180199727-180199727 1:180230592-180230592
44 LHX4 NM_033343.4(LHX4):c.*445G>TSNV Benign 293881 rs57069480 1:180244159-180244159 1:180275024-180275024
45 LHX4 NM_033343.4(LHX4):c.*97T>GSNV Benign 293876 rs145063714 1:180243811-180243811 1:180274676-180274676
46 LHX4 NM_033343.4(LHX4):c.*130C>TSNV Benign 293878 rs59623342 1:180243844-180243844 1:180274709-180274709
47 LHX4 NM_033343.4(LHX4):c.384C>T (p.Asp128=)SNV Benign 293863 rs141139762 1:180235662-180235662 1:180266527-180266527
48 LHX4 NM_033343.4(LHX4):c.452-5T>CSNV Benign 293866 rs2764449 1:180240510-180240510 1:180271375-180271375
49 LHX4 NM_033343.4(LHX4):c.*286G>CSNV Benign 293879 rs80203153 1:180244000-180244000 1:180274865-180274865
50 LHX4 NM_033343.4(LHX4):c.*17C>ASNV Benign 293872 rs116482990 1:180243731-180243731 1:180274596-180274596

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

73
# 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

Sources for Pituitary Hormone Deficiency, Combined, 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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