CPHD3
MCID: PTT047
MIFTS: 28

Pituitary Hormone Deficiency, Combined, 3 (CPHD3)

Categories: Ear diseases, Endocrine diseases, Fetal diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Pituitary Hormone Deficiency, Combined, 3

MalaCards integrated aliases for Pituitary Hormone Deficiency, Combined, 3:

Name: Pituitary Hormone Deficiency, Combined, 3 57 72 13 70
Cphd3 57 20 72
Non-Acquired Combined Pituitary Hormone Deficiency-Sensorineural Hearing Loss-Spine Abnormalities Syndrome 20 58
Non-Acquired Combined Pituitary Hormone Deficiency-Deafness-Rigid Cervical Spine Syndrome 20 58
Pituitary Hormone Deficiency, Combined 3 20 6
Pituitary Hormone Deficiency, Combined, with Rigid Cervical Spine 57
Combined Pituitary Hormone Deficiency with Rigid Cervical Spine 72
Deafness, Sensorineural, with Pituitary Dwarfism 57
Hormone Deficiency, Pituitary, Combined, Type 3 39
Sensorineural Deafness with Pituitary Dwarfism 72
Combined Pituitary Hormone Deficiency Type 3 6
Winkelmann-Bethge-Pfeiffer Syndrome 20

Characteristics:

Orphanet epidemiological data:

58
non-acquired combined pituitary hormone deficiency-sensorineural hearing loss-spine abnormalities syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
pituitary hormone deficiency, combined, 3:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare otorhinolaryngological diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


External Ids:

OMIM® 57 221750
OMIM Phenotypic Series 57 PS613038
MeSH 44 D007018
Orphanet 58 ORPHA231720
UMLS 70 C3489787

Summaries for Pituitary Hormone Deficiency, Combined, 3

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 231720 Definition Non-acquired combined pituitary hormone deficiency- sensorineural hearing loss -spine abnormalities syndrome is a rare, genetic, non-acquired, combined pituitary hormone deficiency disorder characterized by panhypopituitarism (with or without ACTH deficiency) associated with spine abnormalities, including frequent rigid cervical spine and short neck with limited rotation, and variable degrees of sensorineural hearing loss. The anterior pituitary gland is usually abnormal (typically hypoplastic) and rarely a mild developmental delay or intellectual disability may be associated.

MalaCards based summary : Pituitary Hormone Deficiency, Combined, 3, is also known as cphd3. An important gene associated with Pituitary Hormone Deficiency, Combined, 3 is LHX3 (LIM Homeobox 3). Affiliated tissues include pituitary and thyroid, and related phenotypes are short neck and sensorineural hearing impairment

UniProtKB/Swiss-Prot : 72 Pituitary hormone deficiency, combined, 3: Combined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD3 is characterized by a complete deficit in all but one (adrenocorticotropin) anterior pituitary hormone and a rigid cervical spine leading to limited head rotation.

More information from OMIM: 221750 PS613038

Related Diseases for Pituitary Hormone Deficiency, Combined, 3

Symptoms & Phenotypes for Pituitary Hormone Deficiency, Combined, 3

Human phenotypes related to Pituitary Hormone Deficiency, Combined, 3:

58 31 (show all 13)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short neck 58 31 hallmark (90%) Very frequent (99-80%) HP:0000470
2 sensorineural hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000407
3 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
4 pituitary hypothyroidism 58 31 hallmark (90%) Very frequent (99-80%) HP:0008245
5 anterior pituitary hypoplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0010627
6 thoracolumbar kyphoscoliosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0003423
7 gonadotropin deficiency 58 31 hallmark (90%) Very frequent (99-80%) HP:0008213
8 hypothalamic luteinizing hormone-releasing hormone deficiency 58 31 hallmark (90%) Very frequent (99-80%) HP:0012287
9 decreased response to growth hormone stimuation test 31 hallmark (90%) HP:0000824
10 adrenocorticotropic hormone deficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0011748
11 intellectual disability 31 HP:0001249
12 growth hormone deficiency 58 Very frequent (99-80%)
13 pituitary dwarfism 31 HP:0000839

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Endocrine Features:
anterior pituitary hypoplasia
anterior pituitary enlargement

Laboratory Abnormalities:
low or absent growth hormone (gh)
low or absent follicle-stimulating hormone (fsh)
low or absent luteinizing hormone (lh)
low or absent thyroid-stimulating hormone (tsh)
low or absent prolactin (pl)
more
Head And Neck Neck:
short neck with limited rotation

Growth Height:
short stature (if untreated)

Head And Neck Ears:
deafness, sensorineural, variable

Neurologic Central Nervous System:
mental retardation (if untreated)

Clinical features from OMIM®:

221750 (Updated 05-Apr-2021)

Drugs & Therapeutics for Pituitary Hormone Deficiency, Combined, 3

Search Clinical Trials , NIH Clinical Center for Pituitary Hormone Deficiency, Combined, 3

Genetic Tests for Pituitary Hormone Deficiency, Combined, 3

Anatomical Context for Pituitary Hormone Deficiency, Combined, 3

MalaCards organs/tissues related to Pituitary Hormone Deficiency, Combined, 3:

40
Pituitary, Thyroid

Publications for Pituitary Hormone Deficiency, Combined, 3

Articles related to Pituitary Hormone Deficiency, Combined, 3:

# Title Authors PMID Year
1
Novel mutations in LHX3 are associated with hypopituitarism and sensorineural hearing loss. 57 6
18407919 2008
2
Four novel mutations of the LHX3 gene cause combined pituitary hormone deficiencies with or without limited neck rotation. 6 57
17327381 2007
3
Clinical case seminar: a novel LHX3 mutation presenting as combined pituitary hormonal deficiency. 57 6
16394081 2006
4
Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency. 6 57
10835633 2000
5
Specification of pituitary cell lineages by the LIM homeobox gene Lhx3. 57
8638120 1996
6
Two novel LHX3 mutations in patients with combined pituitary hormone deficiency including cervical rigidity and sensorineural hearing loss. 61
28302169 2017

Variations for Pituitary Hormone Deficiency, Combined, 3

ClinVar genetic disease variations for Pituitary Hormone Deficiency, Combined, 3:

6 (show top 50) (show all 81)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 LHX3 NM_178138.6(LHX3):c.332A>G (p.Tyr111Cys) SNV Pathogenic 9021 rs104894117 GRCh37: 9:139091646-139091646
GRCh38: 9:136199800-136199800
2 LHX3 NM_178138.6(LHX3):c.452_454+20del Deletion Pathogenic 9022 rs587776711 GRCh37: 9:139091504-139091526
GRCh38: 9:136199658-136199680
3 LHX3 NM_178138.6(LHX3):c.96del (p.Gly33fs) Deletion Pathogenic 9023 rs587776712 GRCh37: 9:139092583-139092583
GRCh38: 9:136200737-136200737
4 LHX3 NM_178138.6(LHX3):c.629C>T (p.Ala210Val) SNV Pathogenic 9024 rs137854503 GRCh37: 9:139090644-139090644
GRCh38: 9:136198798-136198798
5 LHX3 NM_178138.6(LHX3):c.287_288delinsTCCT (p.Gly96fs) Indel Pathogenic 9025 rs137854504 GRCh37: 9:139091690-139091691
GRCh38: 9:136199844-136199845
6 LHX3 NC_000009.12:g.(?_136197325)_(136205012_?)del Deletion Pathogenic 9026 GRCh37:
GRCh38: 9:136197325-136205012
7 LHX3 NM_178138.6(LHX3):c.672G>A (p.Trp224Ter) SNV Pathogenic 9027 rs137854505 GRCh37: 9:139090601-139090601
GRCh38: 9:136198755-136198755
8 LHX3 NM_178138.6(LHX3):c.80-530_776-454del Deletion Pathogenic 9028 GRCh37: 9:139090043-139093129
GRCh38: 9:136198197-136201283
9 LHX3 NM_178138.6(LHX3):c.133A>T (p.Lys45Ter) SNV Pathogenic 9029 rs137854506 GRCh37: 9:139092546-139092546
GRCh38: 9:136200700-136200700
10 LHX3 NM_178138.6(LHX3):c.1051del (p.Ala351fs) Deletion Pathogenic 1029282 GRCh37: 9:139089314-139089314
GRCh38: 9:136197468-136197468
11 LHX3 NM_178138.6(LHX3):c.920G>C (p.Arg307Pro) SNV Conflicting interpretations of pathogenicity 279837 rs182345541 GRCh37: 9:139089445-139089445
GRCh38: 9:136197599-136197599
12 LHX3 NM_178138.6(LHX3):c.79+1902C>T SNV Uncertain significance 279836 rs375579333 GRCh37: 9:139094878-139094878
GRCh38: 9:136203032-136203032
13 LHX3 NM_178138.6(LHX3):c.964G>A (p.Ala322Thr) SNV Uncertain significance 449975 rs201356862 GRCh37: 9:139089401-139089401
GRCh38: 9:136197555-136197555
14 LHX3 NM_178138.6(LHX3):c.*357G>A SNV Uncertain significance 365808 rs886063700 GRCh37: 9:139088814-139088814
GRCh38: 9:136196968-136196968
15 LHX3 NM_178138.6(LHX3):c.*9C>T SNV Uncertain significance 365814 rs369623778 GRCh37: 9:139089162-139089162
GRCh38: 9:136197316-136197316
16 LHX3 NM_178138.6(LHX3):c.79+1862A>G SNV Uncertain significance 365824 rs886063705 GRCh37: 9:139094918-139094918
GRCh38: 9:136203072-136203072
17 LHX3 NM_178138.6(LHX3):c.145C>T (p.Arg49Cys) SNV Uncertain significance 365822 rs781049722 GRCh37: 9:139092534-139092534
GRCh38: 9:136200688-136200688
18 LHX3 NM_178138.6(LHX3):c.*501A>T SNV Uncertain significance 365806 rs886063698 GRCh37: 9:139088670-139088670
GRCh38: 9:136196824-136196824
19 LHX3 NM_178138.6(LHX3):c.*638G>T SNV Uncertain significance 365803 rs374699388 GRCh37: 9:139088533-139088533
GRCh38: 9:136196687-136196687
20 LHX3 NM_178138.6(LHX3):c.79+1813G>C SNV Uncertain significance 365827 rs886063706 GRCh37: 9:139094967-139094967
GRCh38: 9:136203121-136203121
21 LHX3 NM_178138.6(LHX3):c.*719C>T SNV Uncertain significance 914236 GRCh37: 9:139088452-139088452
GRCh38: 9:136196606-136196606
22 LHX3 NM_178138.6(LHX3):c.1092C>A (p.Asn364Lys) SNV Uncertain significance 914277 GRCh37: 9:139089273-139089273
GRCh38: 9:136197427-136197427
23 LHX3 NM_178138.6(LHX3):c.1024A>G (p.Thr342Ala) SNV Uncertain significance 914278 GRCh37: 9:139089341-139089341
GRCh38: 9:136197495-136197495
24 LHX3 NM_178138.6(LHX3):c.966C>T (p.Ala322=) SNV Uncertain significance 914279 GRCh37: 9:139089399-139089399
GRCh38: 9:136197553-136197553
25 LHX3 NM_178138.6(LHX3):c.915G>A (p.Gln305=) SNV Uncertain significance 765894 rs548140963 GRCh37: 9:139089450-139089450
GRCh38: 9:136197604-136197604
26 LHX3 NM_178138.6(LHX3):c.*715C>A SNV Uncertain significance 914718 GRCh37: 9:139088456-139088456
GRCh38: 9:136196610-136196610
27 LHX3 NM_178138.6(LHX3):c.*692C>T SNV Uncertain significance 914719 GRCh37: 9:139088479-139088479
GRCh38: 9:136196633-136196633
28 LHX3 NM_178138.6(LHX3):c.*637T>C SNV Uncertain significance 914720 GRCh37: 9:139088534-139088534
GRCh38: 9:136196688-136196688
29 LHX3 NM_178138.6(LHX3):c.*570C>A SNV Uncertain significance 914721 GRCh37: 9:139088601-139088601
GRCh38: 9:136196755-136196755
30 LHX3 NM_178138.6(LHX3):c.*518G>A SNV Uncertain significance 914722 GRCh37: 9:139088653-139088653
GRCh38: 9:136196807-136196807
31 LHX3 NM_178138.6(LHX3):c.812G>A (p.Gly271Asp) SNV Uncertain significance 914777 GRCh37: 9:139089553-139089553
GRCh38: 9:136197707-136197707
32 LHX3 NM_178138.6(LHX3):c.804G>C (p.Pro268=) SNV Uncertain significance 763063 rs771201500 GRCh37: 9:139089561-139089561
GRCh38: 9:136197715-136197715
33 LHX3 NM_178138.6(LHX3):c.622C>T (p.Arg208Cys) SNV Uncertain significance 914778 GRCh37: 9:139090651-139090651
GRCh38: 9:136198805-136198805
34 LHX3 NM_178138.6(LHX3):c.597C>T (p.Arg199=) SNV Uncertain significance 914779 GRCh37: 9:139090763-139090763
GRCh38: 9:136198917-136198917
35 LHX3 NM_178138.6(LHX3):c.1092C>T (p.Asn364=) SNV Uncertain significance 365815 rs886063702 GRCh37: 9:139089273-139089273
GRCh38: 9:136197427-136197427
36 LHX3 NM_178138.6(LHX3):c.*55G>A SNV Uncertain significance 365812 rs543364659 GRCh37: 9:139089116-139089116
GRCh38: 9:136197270-136197270
37 LHX3 NM_178138.6(LHX3):c.860C>T (p.Ser287Leu) SNV Uncertain significance 365817 rs748322395 GRCh37: 9:139089505-139089505
GRCh38: 9:136197659-136197659
38 LHX3 NM_178138.6(LHX3):c.*790C>T SNV Uncertain significance 365801 rs572411652 GRCh37: 9:139088381-139088381
GRCh38: 9:136196535-136196535
39 LHX3 NM_178138.6(LHX3):c.*857C>T SNV Uncertain significance 365798 rs886063696 GRCh37: 9:139088314-139088314
GRCh38: 9:136196468-136196468
40 LHX3 NM_178138.6(LHX3):c.79+1829G>A SNV Uncertain significance 365825 rs551389075 GRCh37: 9:139094951-139094951
GRCh38: 9:136203105-136203105
41 LHX3 NM_178138.6(LHX3):c.*161C>A SNV Uncertain significance 365810 rs886063701 GRCh37: 9:139089010-139089010
GRCh38: 9:136197164-136197164
42 LHX3 NM_178138.6(LHX3):c.*409G>T SNV Uncertain significance 365807 rs886063699 GRCh37: 9:139088762-139088762
GRCh38: 9:136196916-136196916
43 LHX3 NM_178138.6(LHX3):c.*582G>A SNV Uncertain significance 365804 rs879304888 GRCh37: 9:139088589-139088589
GRCh38: 9:136196743-136196743
44 LHX3 NM_178138.6(LHX3):c.*1031A>G SNV Uncertain significance 365796 rs569655668 GRCh37: 9:139088140-139088140
GRCh38: 9:136196294-136196294
45 LHX3 NM_178138.6(LHX3):c.*32G>A SNV Uncertain significance 365813 rs771392788 GRCh37: 9:139089139-139089139
GRCh38: 9:136197293-136197293
46 LHX3 NM_178138.6(LHX3):c.79+1967C>A SNV Uncertain significance 365823 rs759584117 GRCh37: 9:139094813-139094813
GRCh38: 9:136202967-136202967
47 LHX3 NM_178138.6(LHX3):c.441C>T (p.Thr147=) SNV Uncertain significance 365821 rs200521449 GRCh37: 9:139091537-139091537
GRCh38: 9:136199691-136199691
48 LHX3 NM_178138.6(LHX3):c.*554C>T SNV Uncertain significance 365805 rs886063697 GRCh37: 9:139088617-139088617
GRCh38: 9:136196771-136196771
49 LHX3 NM_178138.6(LHX3):c.776-15C>A SNV Uncertain significance 365818 rs376405589 GRCh37: 9:139089604-139089604
GRCh38: 9:136197758-136197758
50 LHX3 NM_178138.6(LHX3):c.*773G>A SNV Uncertain significance 365802 rs148781569 GRCh37: 9:139088398-139088398
GRCh38: 9:136196552-136196552

UniProtKB/Swiss-Prot genetic disease variations for Pituitary Hormone Deficiency, Combined, 3:

72
# Symbol AA change Variation ID SNP ID
1 LHX3 p.Tyr111Cys VAR_010713 rs104894117
2 LHX3 p.Ala210Val VAR_063240 rs137854503

Expression for Pituitary Hormone Deficiency, Combined, 3

Search GEO for disease gene expression data for Pituitary Hormone Deficiency, Combined, 3.

Pathways for Pituitary Hormone Deficiency, Combined, 3

GO Terms for Pituitary Hormone Deficiency, Combined, 3

Sources for Pituitary Hormone Deficiency, Combined, 3

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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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