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AEXS
MCID: ARM004
MIFTS: 48

Aromatase Excess Syndrome (AEXS)

Categories: Bone diseases, Endocrine diseases, Genetic diseases, Rare diseases, Reproductive diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Aromatase Excess Syndrome

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MalaCards integrated aliases for Aromatase Excess Syndrome:

Name: Aromatase Excess Syndrome 56 12 74 52 25 58 73 36 29 13 6 15 39 71
Aexs 56 12 52 25 58 73
Hereditary Prepubertal Gynecomastia 12 52 58
Increased Aromatase Activity 12 25 73
Familial Hyperestrogenism 12 52 58
Familial Gynecomastia Due to Increased Aromatase Activity 25 73
Aromatase Activity, Increased 56 52
Hereditary Gynecomastia 25 73
Gynecomastia, Familial 71
Familial Gynecomastia 73

Characteristics:

Orphanet epidemiological data:

58
aromatase excess syndrome
Inheritance: Autosomal dominant;

OMIM:

56
Inheritance:
male-limited autosomal dominant vs. autosomal recessive or x-linked


HPO:

31
aromatase excess syndrome:
Inheritance autosomal dominant inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases
Anatomical: Reproductive diseases Endocrine diseases Bone diseases
See all MalaCards categories (disease lists)
ICD10: 32 33
Orphanet: 58  
Rare gynaecological and obstetric diseases
Rare endocrine diseases


External Ids:

Disease Ontology 12 DOID:0090122
OMIM 56 139300
KEGG 36 H00794
MeSH 43 D006177
ICD10 32 E30.1
ICD10 via Orphanet 33 E30.1
UMLS via Orphanet 72 C1970109
Orphanet 58 ORPHA178345
UMLS 71 C1844375 C1970109
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Summaries for Aromatase Excess Syndrome

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Genetics Home Reference : 25 Aromatase excess syndrome is a condition characterized by elevated levels of the female sex hormone estrogen in both males and females. Males with aromatase excess syndrome experience breast enlargement (gynecomastia) in late childhood or adolescence. The bones of affected males grow and develop more quickly and stop growing sooner than usual (advanced bone age). As a result males have an early growth spurt, typically during late childhood, with short stature as an adult. Affected females rarely show signs and symptoms of the condition, but they may have increased breast growth (macromastia), irregular menstrual periods, and short stature. The ability to have children (fertility) is usually normal in both males and females with aromatase excess syndrome.

MalaCards based summary : Aromatase Excess Syndrome, also known as aexs, is related to androgen insensitivity, partial and aromatase deficiency. An important gene associated with Aromatase Excess Syndrome is CYP19A1 (Cytochrome P450 Family 19 Subfamily A Member 1), and among its related pathways/superpathways are Steroid hormone biosynthesis and Relaxin signaling pathway. The drugs Letrozole and Hormone Antagonists have been mentioned in the context of this disorder. Affiliated tissues include bone, breast and liver, and related phenotypes are short stature and gynecomastia

Disease Ontology : 12 A reproductive system disease characterized by increased extraglandular aromatization of steroids resulting in heterosexual precocity in males and isosexual precocity in females, and has material basis in autosomal dominant inheritance of fusion of the aromatase gene (CYP19A1) with various partners, brought about by translocations and resulting in gain of function of the CYP19A1 gene.

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 178345 Definition A rare, genetic endocrine disease characterized by increased levels of estrogen due to elevated extraglandular aromatase activity. Males present with heterosexual precocious puberty which manifests with pre- or peripubertal onset of gynecomastia , premature growth spurt, accelerated bone maturation resulting in decreased adult stature, and may present mild hypogonadotropic hypogonadism . Female patients may have isosexual precocious puberty or not have any manifestations at all. Visit the Orphanet disease page for more resources.

OMIM : 56 Aromatase excess syndrome is an autosomal dominant disorder characterized by increased extraglandular aromatization of steroids that presents with heterosexual precocity in males and isosexual precocity in females (Tiulpakov et al., 2005). (139300)

KEGG : 36 Aromatase excess syndrome (AEXS) is a rare disorder characterized by gynecomastia. Excessive expression of aromatase, an enzyme that plays a crucial role in the estrogen biosynthesis, causes pre- or peripubertal onset gynecomastia, advanced bone age such as early fusion of epiphyses, and short stature in affected males. Female patients experience premature breast development.

UniProtKB/Swiss-Prot : 73 Aromatase excess syndrome: An autosomal dominant disorder characterized by increased extraglandular aromatization of steroids that presents with heterosexual precocity in males and isosexual precocity in females.

Wikipedia : 74 Aromatase excess syndrome (AES or AEXS) is a rare genetic and endocrine syndrome which is characterized... more...

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Related Diseases for Aromatase Excess Syndrome

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Diseases related to Aromatase Excess Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 155)
# Related Disease Score Top Affiliating Genes
1 androgen insensitivity, partial 30.5 SHBG CYP19A1
2 aromatase deficiency 30.0 ESR1 CYP19A1
3 hyperprolactinemia 29.7 SHBG POMC IGF1
4 hypogonadism 29.3 SHBG LEP IGF1 CYP19A1
5 infertility 29.1 SHBG ESR2 EPPIN CYP19A1
6 polycystic ovary syndrome 28.8 SHBG POMC LEP IGF1 CYP19A1
7 gynecomastia 28.5 SHBG POMC LEP ESR2 ESR1 CYP19A1
8 estrogen excess 28.5 SHBG ESR2 ESR1 EPPIN CYP19A1 CGNL1
9 adrenal rest tumor 10.4 POMC EPPIN
10 premenstrual tension 10.4 SHBG POMC
11 hypoactive sexual desire disorder 10.4 SHBG CYP19A1
12 hypoglycemic coma 10.4 POMC EPPIN
13 alopecia, androgenetic, 1 10.4 SHBG CYP19A1
14 infant gynecomastia 10.4
15 complete androgen insensitivity syndrome 10.3 SHBG CYP19A1
16 atrophic vulva 10.3 SHBG ESR1
17 urethral benign neoplasm 10.3 ESR1 AMACR
18 juvenile nasopharyngeal angiofibroma 10.3 ESR1 CYP19A1
19 testicular torsion 10.2 EPPIN CGB5
20 pituitary infarct 10.2 POMC IGF1
21 functionless pituitary adenoma 10.2 POMC IGF1
22 acidophil adenoma 10.2 POMC IGF1
23 steroid inherited metabolic disorder 10.2 SHBG POMC CYP19A1
24 fasting hypoglycemia 10.2 POMC IGF1
25 pseudohermaphroditism 10.2 POMC EPPIN CYP19A1
26 hormone producing pituitary cancer 10.2 POMC IGF1
27 lipoid congenital adrenal hyperplasia 10.2 SHBG POMC CYP19A1
28 vaginal discharge 10.2 ESR1 CYP19A1
29 luteoma 10.2 SHBG EPPIN CYP19A1
30 ovarian hyperstimulation syndrome 10.2 SHBG CYP19A1 CGB5
31 syndromic obesity 10.2 POMC LEP
32 hypertrophy of breast 10.2 ESR1 CYP19A1
33 graves disease 1 10.2 SHBG POMC
34 sheehan syndrome 10.2 POMC IGF1
35 classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency 10.2 POMC LEP
36 impotence 10.1 SHBG POMC EPPIN
37 pituitary apoplexy 10.1 POMC IGF1
38 sick building syndrome 10.1 POMC LEP
39 hypothalamic disease 10.1 POMC LEP
40 marasmus 10.1 SHBG IGF1
41 empty sella syndrome 10.1 POMC IGF1
42 atypical depressive disorder 10.1 POMC LEP
43 glucocorticoid deficiency 1 10.1 POMC LEP
44 premature menopause 10.1 EPPIN CYP19A1
45 46,xy sex reversal 10.1 POMC ESR1 CYP19A1
46 hyperpituitarism 10.1 POMC IGF1
47 androgenic alopecia 10.0 SHBG IGF1 CYP19A1
48 adrenal gland disease 10.0 POMC IGF1 EPPIN
49 sebaceous gland disease 10.0 SHBG POMC IGF1
50 sexual disorder 10.0 SHBG POMC IGF1

Graphical network of the top 20 diseases related to Aromatase Excess Syndrome:



Diseases related to Aromatase Excess Syndrome
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Symptoms & Phenotypes for Aromatase Excess Syndrome

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Human phenotypes related to Aromatase Excess Syndrome:

31
# Description HPO Frequency HPO Source Accession
1 short stature 31 HP:0004322
2 gynecomastia 31 HP:0000771
3 accelerated skeletal maturation 31 HP:0005616

Symptoms via clinical synopsis from OMIM:

56
Thorax:
gynecomastia

Clinical features from OMIM:

139300

MGI Mouse Phenotypes related to Aromatase Excess Syndrome:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 adipose tissue MP:0005375 9.97 AMACR CYP19A1 DMXL2 ESR1 ESR2 IGF1
2 integument MP:0010771 9.87 CYP19A1 ESR1 ESR2 IGF1 LEP POMC
3 liver/biliary system MP:0005370 9.8 AMACR CYP19A1 ESR1 ESR2 LEP POMC
4 muscle MP:0005369 9.63 CYP19A1 ESR1 ESR2 IGF1 LEP TLN2
5 neoplasm MP:0002006 9.43 DMXL2 ESR1 ESR2 IGF1 LEP POMC
6 renal/urinary system MP:0005367 9.1 CYP19A1 ESR1 ESR2 IGF1 LEP POMC
Sources

Drugs & Therapeutics for Aromatase Excess Syndrome

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Drugs for Aromatase Excess Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 20)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Letrozole Approved, Investigational Phase 4 112809-51-5 3902
2 Hormone Antagonists Phase 4
3 Hormones Phase 4
4 Estrogen Antagonists Phase 4
5 Estrogen Receptor Antagonists Phase 4
6 Estrogens Phase 4
7 Liver Extracts Phase 4
8
Dehydroepiandrosterone Approved, Investigational, Nutraceutical Phase 2, Phase 3 53-43-0 9860744
9 Adjuvants, Immunologic Phase 2, Phase 3
10 Immunologic Factors Phase 2, Phase 3
11 DHEA (Dehydroepiandrosterone) Phase 2, Phase 3
12
Estradiol Approved, Investigational, Vet_approved 50-28-2 5757
13
Polyestradiol phosphate Approved 28014-46-2
14 Mitogens
15 Estradiol 17 beta-cypionate
16 Follicle Stimulating Hormone
17 Estradiol 3-benzoate
18 Aromatase Inhibitors
19 Calcium, Dietary
20
Calcium Nutraceutical 7440-70-2 271

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Influence of the Aromatase Inhibitor Letrozole on Heart and Liver Function in Obese Men Unknown status NCT02097680 Phase 4 Letrozole;Placebo
2 A Randomized Placebo-Controlled Trial of Dehydroepiandrosterone (DHEA) Treatment for Two Months Before Starting Ovulation Induction for in Vitro Fertilization (IVF) Terminated NCT00419913 Phase 2, Phase 3
3 Aromatase Activity and Ovarian Growth Factors in Preovulatory Follicles Unknown status NCT00334971
4 Aromatase Inhibitors: Skeletal Effects and the Role of CYP19 Gene Polymorphisms Completed NCT00603967

Search NIH Clinical Center for Aromatase Excess Syndrome

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Genetic Tests for Aromatase Excess Syndrome

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Genetic tests related to Aromatase Excess Syndrome:

# Genetic test Affiliating Genes
1 Aromatase Excess Syndrome 29 CYP19A1
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Anatomical Context for Aromatase Excess Syndrome

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MalaCards organs/tissues related to Aromatase Excess Syndrome:

40
Bone, Breast, Liver, Heart
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Publications for Aromatase Excess Syndrome

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Articles related to Aromatase Excess Syndrome:

(show all 29)
# Title Authors PMID Year
1
A potential rearrangement between CYP19 and TRPM7 genes on chromosome 15q21.2 as a cause of aromatase excess syndrome. 56 6 61
15811932 2005
2
Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene. 6 56
12736278 2003
3
Dominant transmission of prepubertal gynecomastia due to serum estrone excess: hormonal, biochemical, and genetic analysis in a large kindred. 61 56
15483104 2005
4
The aromatase excess syndrome is associated with feminization of both sexes and autosomal dominant transmission of aberrant P450 aromatase gene transcription. 61 56
9543166 1998
5
Aromatase p450 expression in a feminizing adrenal adenoma presenting as isosexual precocious puberty. 56
11158024 2001
6
Familial adrenal feminization probably due to increased steroid aromatization. 56
1478630 1992
7
Familial gynecomastia with increased extraglandular aromatization of plasma carbon19-steroids. 56
3924954 1985
8
Massive extranglandular aromatization of plasma androstenedione resulting in feminization of a prepubertal boy. 56
874104 1977
9
Familial gynecomastia without hypogonadism: a report of three cases in one family. 56
13998571 1962
10
Hereditary gynaecomastia. 56
13762869 1960
11
Aromatase excess syndrome in a Chinese boy due to a novel duplication at 15q21.2. 61
30530883 2019
12
Leaky Cauldron on the Dark Land: Understanding Memory Side-Channel Hazards in SGX. 61
30853868 2017
13
The Idiopathic Pulmonary Fibrosis Clinical Research Network (IPFnet): diagnostic and adjudication processes. 61
26111071 2015
14
Aromatase excess syndrome in a family with upstream deletion of CYP19A1. 61
24102311 2014
15
Understanding the pathological manifestations of aromatase excess syndrome: lessons for clinical diagnosis. 61
25264451 2014
16
Lack of genomic rearrangements involving the aromatase gene CYP19A1 in breast cancer. 61
23625277 2014
17
Aromatase excess syndrome: a rare autosomal dominant disorder leading to pre- or peri-pubertal onset gynecomastia. 61
24716396 2014
18
Genomic basis of aromatase excess syndrome: recombination- and replication-mediated rearrangements leading to CYP19A1 overexpression. 61
24064691 2013
19
Aromatase excess syndrome presenting with prepubertal gynecomastia in an Egyptian child with type 1 neurofibromatosis. 61
24497716 2013
20
Molecular bases and phenotypic determinants of aromatase excess syndrome. 61
22319526 2012
21
Aromatase inhibitors in pediatrics. 61
22024975 2011
22
Aromatase excess syndrome: identification of cryptic duplications and deletions leading to gain of function of CYP19A1 and assessment of phenotypic determinants. 61
21470988 2011
23
Akhenaten and the strange physiques of Egypt's 18th dynasty. 61
19380856 2009
24
Disseminated blue naevus and malignant blue naevus associated with excessive aromatase syndrome. 61
18462445 2008
25
Regional rearrangements in chromosome 15q21 cause formation of cryptic promoters for the CYP19 (aromatase) gene. 61
17584767 2007
26
[Familial precocious puberty -- a variant of norm or pathology?]. 61
16704862 2006
27
Regulation of aromatase expression in estrogen-responsive breast and uterine disease: from bench to treatment. 61
16109840 2005
28
Prepubertal gynaecomastia caused by medication or the aromatase excess syndrome. 61
15579195 2004
29
Aromatase and gynecomastia. 61
10731125 1999
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Variations for Aromatase Excess Syndrome

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ClinVar genetic disease variations for Aromatase Excess Syndrome:

6 ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CYP19A1 CYP19A1, INV, CGNL1 PROMOTERundetermined variant Pathogenic 17824
2 CYP19A1 CYP19A1, INV, TMOD3 PROMOTERundetermined variant Pathogenic 17825
3 CYP19A1 CYP19A1, CYP19A1/TRPM7 FUSIONundetermined variant Pathogenic 17827

Copy number variations for Aromatase Excess Syndrome from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 93187 15 49287545 49418087 Deletion CYP19A1 Aromatase excess syndrome
2 93192 15 49421004 49487501 Deletion GLDN Aromatase excess syndrome
3 93201 15 49527230 49702259 Deletion DMXL2 Aromatase excess syndrome
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Expression for Aromatase Excess Syndrome

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Search GEO for disease gene expression data for Aromatase Excess Syndrome.
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Pathways for Aromatase Excess Syndrome

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Pathways related to Aromatase Excess Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 Steroid hormone biosynthesis hsa00140

Pathways related to Aromatase Excess Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Relaxin signaling pathway 36
Show member pathways
 12.05 POMC IGF1 ESR2 ESR1
2
Peptide hormone metabolism 65
Show member pathways
 11.52 POMC LEP IGF1 CGB5
3
Apoptosis and survival_Anti-apoptotic action of nuclear ESR1 and ESR2 22
10.85 ESR2 ESR1
4
Plasma membrane estrogen receptor signaling 1
10.78 ESR2 ESR1
5
MNAR-PELP1 and Estrogen Receptor Interaction 63
10.68 ESR2 ESR1
6
Antipsychotics Pathway (Metabolic Side Effects), Pharmacodynamics 60
10.56 POMC LEP
7
Aromatase Inhibitor Pathway (Breast Cell), Pharmacodynamics 60
9.4 ESR2 ESR1 CYP19A1
Sources

GO Terms for Aromatase Excess Syndrome

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Biological processes related to Aromatase Excess Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 intracellular estrogen receptor signaling pathway GO:0030520 9.37 ESR2 ESR1
2 response to estradiol GO:0032355 9.33 LEP ESR1 CYP19A1
3 uterus development GO:0060065 9.32 ESR1 CYP19A1
4 androgen metabolic process GO:0008209 9.26 ESR1 CYP19A1
5 bile acid metabolic process GO:0008206 8.96 LEP AMACR
6 bone mineralization involved in bone maturation GO:0035630 8.62 LEP IGF1

Molecular functions related to Aromatase Excess Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 estrogen receptor activity GO:0030284 9.26 ESR2 ESR1
2 estrogen response element binding GO:0034056 9.16 ESR2 ESR1
3 steroid binding GO:0005496 9.13 SHBG ESR2 ESR1
4 hormone activity GO:0005179 8.92 POMC LEP IGF1 CGB5
Sources

Sources for Aromatase Excess Syndrome

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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
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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