XLAG
MCID: CHR525
MIFTS: 36

Chromosome Xq26.3 Duplication Syndrome (XLAG)

Categories: Endocrine diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Chromosome Xq26.3 Duplication Syndrome

MalaCards integrated aliases for Chromosome Xq26.3 Duplication Syndrome:

Name: Chromosome Xq26.3 Duplication Syndrome 57 25 43 29 6 70
X-Linked Acrogigantism 57 25 43 58
X-Lag 25 43 58
Xlag 57 25 43
Chromosome Xq26 Microduplication Syndrome 57 43
Infantile Gigantism Due to Pituitary Hyperplasia 58
Hereditary Pituitary Hyperplasia 58
X-Linked Acrogigantism Syndrome 43
Hereditary Infantile Gigantism 58
X-Linked Acrogigantism; Xlag 57
Familial Infantile Gigantism 58
Lissencephaly, X-Linked, 2 70

Characteristics:

Orphanet epidemiological data:

58
x-linked acrogigantism
Inheritance: X-linked dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
x-linked dominant

Miscellaneous:
onset of overgrowth in the first year of life (in most cases)
onset of overgrowth in second to third month of life (in some cases)


HPO:

31
chromosome xq26.3 duplication syndrome:
Inheritance x-linked dominant inheritance


GeneReviews:

25
Penetrance All heterozygous females and hemizygous males described to date were affected....

Classifications:

Orphanet: 58  
Rare endocrine diseases


Summaries for Chromosome Xq26.3 Duplication Syndrome

MedlinePlus Genetics : 43 X-linked acrogigantism (X-LAG) is a condition that causes abnormally fast growth beginning early in life. Babies with this condition are a normal size at birth but begin to grow rapidly in infancy or early childhood, and affected children are taller than their peers.This rapid growth is caused by an abnormality of the pituitary gland. The pituitary gland, which is found at the base of the brain, produces hormones that control many important body functions, including growth. Individuals with X-LAG may have the condition as a result of enlargement (hyperplasia) of the gland or development of a noncancerous tumor in the gland (called a pituitary adenoma). Rarely, an affected individual has both pituitary hyperplasia and an adenoma. The abnormal gland releases excess amounts of growth hormone, a hormone that normally helps direct growth of the body's bones and tissues. Some people with X-LAG also have excess amounts of a hormone called growth hormone releasing hormone (GHRH), which is produced by a part of the brain called the hypothalamus. This hormone stimulates the release of growth hormone from the pituitary gland.Some people with X-LAG have additional signs and symptoms such as facial features that are described as coarse; disproportionately large hands or feet (acral enlargement); an increased appetite; and a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety.

MalaCards based summary : Chromosome Xq26.3 Duplication Syndrome, also known as x-linked acrogigantism, is related to lissencephaly, x-linked, 2 and lissencephaly, and has symptoms including snoring and thick skin. An important gene associated with Chromosome Xq26.3 Duplication Syndrome is CXDUPQ26.3 (Chromosome Xq26.3 Duplication Syndrome). Affiliated tissues include pituitary, hypothalamus and thyroid, and related phenotypes are tall stature and growth hormone excess

OMIM® : 57 X-linked acrogigantism (XLAG), due to microduplications of chromosome Xq26.3, is characterized by excessive growth, usually beginning during the first year of life in previously normal infants. The overgrowth is caused by growth hormone (GH1; 139250) hypersecretion from pituitary hyperplasia and/or a pituitary macroadenoma. XLAG can occur as a sporadic condition or present as familial isolated pituitary adenomas (FIPAs) in acrogigantism kindreds (Beckers et al., 2015). (300942) (Updated 20-May-2021)

GeneReviews: NBK476671

Related Diseases for Chromosome Xq26.3 Duplication Syndrome

Graphical network of the top 20 diseases related to Chromosome Xq26.3 Duplication Syndrome:



Diseases related to Chromosome Xq26.3 Duplication Syndrome

Symptoms & Phenotypes for Chromosome Xq26.3 Duplication Syndrome

Human phenotypes related to Chromosome Xq26.3 Duplication Syndrome:

58 31 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 tall stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0000098
2 growth hormone excess 58 31 hallmark (90%) Very frequent (99-80%) HP:0000845
3 increased circulating prolactin concentration 58 31 hallmark (90%) Very frequent (99-80%) HP:0000870
4 increased serum insulin-like growth factor 1 58 31 hallmark (90%) Very frequent (99-80%) HP:0030269
5 hyperhidrosis 58 31 frequent (33%) Frequent (79-30%) HP:0000975
6 sleep apnea 58 31 frequent (33%) Frequent (79-30%) HP:0010535
7 coarse facial features 58 31 frequent (33%) Frequent (79-30%) HP:0000280
8 polyphagia 58 31 frequent (33%) Frequent (79-30%) HP:0002591
9 pituitary adenoma 58 31 frequent (33%) Frequent (79-30%) HP:0002893
10 fasting hyperinsulinemia 58 31 frequent (33%) Frequent (79-30%) HP:0008283
11 abnormal oral glucose tolerance 58 31 frequent (33%) Frequent (79-30%) HP:0004924
12 snoring 58 31 frequent (33%) Frequent (79-30%) HP:0025267
13 increased body mass index 58 31 frequent (33%) Frequent (79-30%) HP:0031418
14 abnormality of optic chiasm morphology 58 31 frequent (33%) Frequent (79-30%) HP:0025163
15 decreased thyroid-stimulating hormone level 58 31 frequent (33%) Frequent (79-30%) HP:0031098
16 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
17 delayed puberty 58 31 occasional (7.5%) Occasional (29-5%) HP:0000823
18 abnormality of the cardiovascular system 58 31 occasional (7.5%) Occasional (29-5%) HP:0001626
19 abnormality of the skeletal system 58 31 occasional (7.5%) Occasional (29-5%) HP:0000924
20 diabetes insipidus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000873
21 headache 58 31 occasional (7.5%) Occasional (29-5%) HP:0002315
22 acanthosis nigricans 58 31 occasional (7.5%) Occasional (29-5%) HP:0000956
23 large hands 58 31 occasional (7.5%) Occasional (29-5%) HP:0001176
24 hypogonadism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000135
25 visual field defect 58 31 occasional (7.5%) Occasional (29-5%) HP:0001123
26 abdominal distention 58 31 occasional (7.5%) Occasional (29-5%) HP:0003270
27 adrenocorticotropic hormone deficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0011748
28 long foot 58 31 occasional (7.5%) Occasional (29-5%) HP:0001833
29 enlarged pituitary gland 58 31 occasional (7.5%) Occasional (29-5%) HP:0012505
30 diastema 58 31 occasional (7.5%) Occasional (29-5%) HP:0000699
31 seizure 31 occasional (7.5%) HP:0001250
32 intellectual disability 58 31 very rare (1%) Very rare (<4-1%) HP:0001249
33 seizures 58 Occasional (29-5%)
34 abnormality of the nervous system 58 Very rare (<4-1%)
35 accelerated skeletal maturation 31 HP:0005616
36 thickened skin 58 Frequent (79-30%)
37 hypopituitarism 58 Occasional (29-5%)
38 abnormality of the pituitary gland 58 Very frequent (99-80%)
39 ventricular hypertrophy 31 HP:0001714
40 body odor 31 HP:0500001

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Respiratory Nasopharynx:
sleep apnea
snoring

Skeletal Hands:
large hands

Endocrine Features:
pituitary adenoma
increased sweating at early age
prominent body odor
elevated growth hormone (gh) levels
elevated igf1 levels
more
Skeletal Feet:
large feet

Abdomen Gastrointestinal:
increased appetite

Growth Height:
tall stature (+3.4 sd)
increased height velocity (+6.1 sd)

Cardiovascular Heart:
ventricular hypertrophy, mild (noted in 1 patient)

Skin Nails Hair Skin:
acanthosis nigricans
skin thickening

Neurologic Central Nervous System:
pituitary adenoma

Skeletal:
advanced bone age

Head And Neck Face:
acromegaly
coarse facies

Growth Weight:
increased weight

Head And Neck Teeth:
widening of interdental spaces

Clinical features from OMIM®:

300942 (Updated 20-May-2021)

UMLS symptoms related to Chromosome Xq26.3 Duplication Syndrome:


snoring; thick skin

Drugs & Therapeutics for Chromosome Xq26.3 Duplication Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase 2/3 Open-Label Trial to Evaluate Enoblituzumab in Combination With MGA012 or MGD013 in the First-Line Treatment of Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Withdrawn NCT04129320 Phase 2, Phase 3
2 A Phase 2 Open-Label Trial to Evaluate Enoblituzumab in Combination With Retifanlimab or Tebotelimab in the First-Line Treatment of Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Recruiting NCT04634825 Phase 2

Search NIH Clinical Center for Chromosome Xq26.3 Duplication Syndrome

Genetic Tests for Chromosome Xq26.3 Duplication Syndrome

Genetic tests related to Chromosome Xq26.3 Duplication Syndrome:

# Genetic test Affiliating Genes
1 Chromosome Xq26.3 Duplication Syndrome 29 GPR101

Anatomical Context for Chromosome Xq26.3 Duplication Syndrome

MalaCards organs/tissues related to Chromosome Xq26.3 Duplication Syndrome:

40
Pituitary, Hypothalamus, Thyroid, Bone

Publications for Chromosome Xq26.3 Duplication Syndrome

Articles related to Chromosome Xq26.3 Duplication Syndrome:

(show top 50) (show all 60)
# Title Authors PMID Year
1
Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study. 61 25 57
27245663 2016
2
Somatic GPR101 Duplication Causing X-Linked Acrogigantism (XLAG)-Diagnosis and Management. 57 25 61
26982009 2016
3
Somatic mosaicism underlies X-linked acrogigantism syndrome in sporadic male subjects. 25 57 61
26935837 2016
4
GHRH excess and blockade in X-LAG syndrome. 57 61 25
26671997 2016
5
X-linked acrogigantism syndrome: clinical profile and therapeutic responses. 61 25 57
25712922 2015
6
Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation. 57 25 61
25470569 2014
7
Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome. 57 25
26607152 2016
8
Gigantism due to pituitary mammosomatotroph hyperplasia. 57 25
2164153 1990
9
Paleogenetic study of ancient DNA suggestive of X-linked acrogigantism. 25 61
28049632 2017
10
Childhood acromegaly due to X-linked acrogigantism: long term follow-up. 25 61
27631333 2016
11
Characterization of GPR101 transcript structure and expression patterns. 25 61
27282544 2016
12
Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients. 25 61
26187128 2015
13
Hereditary pituitary hyperplasia with infantile gigantism. 57
21976722 2011
14
Eight-year follow-up of a child with a GH/prolactin-secreting adenoma: efficacy of pegvisomant therapy. 57
20190543 2010
15
Pituitary gigantism in a 31 month old girl: endocrine studies and successful response to hypophysectomy. 57
6278015 1981
16
PRKAR1A mutation causing pituitary-dependent Cushing disease in a patient with Carney complex. 25
28522647 2017
17
Corticotropinoma as a Component of Carney Complex. 25
29264542 2017
18
MEN1 redefined, a clinical comparison of mutation-positive and mutation-negative patients. 25
27842554 2016
19
Novel Genetic Causes of Pituitary Adenomas. 25
27742789 2016
20
Mortality in acromegaly: a 20-year follow-up study. 25
27185871 2016
21
PRKACB and Carney complex. 25
24571725 2014
22
Familial pituitary apoplexy as the only presentation of a novel AIP mutation. 25
24025584 2013
23
A consensus on the diagnosis and treatment of acromegaly complications. 25
22903574 2013
24
The effects of long-term growth hormone and insulin-like growth factor-1 exposure on the development of cardiovascular, cerebrovascular and metabolic co-morbidities in treated patients with acromegaly. 25
21521288 2011
25
Arthropathy in acromegaly. 25
21092848 2010
26
Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002). 25
20427401 2010
27
The pathology of the ulnar nerve in acromegaly. 25
18632873 2008
28
Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1 multicenter study. 25
11836268 2002
29
Congenital hypopituitarism in two brothers with a duplication of the 'acrogigantism gene' GPR101: clinical findings and review of the literature. 61
33184694 2021
30
The clinical aspects of pituitary tumour genetics. 61
33543431 2021
31
Genetics of Acromegaly and Gigantism. 61
33805450 2021
32
The X-linked acrogigantism-associated gene gpr101 is a regulator of early embryonic development and growth in zebrafish. 61
33248229 2021
33
A Chinese case of X-linked acrogigantism and systemic review. 61
33049741 2020
34
GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11. 61
32958754 2020
35
HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: The roles of AIP and GPR101 in familial isolated pituitary adenomas (FIPA). 61
32083999 2020
36
HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: GPR101, an orphan GPCR with roles in growth and pituitary tumorigenesis. 61
32240984 2020
37
The Genetics of Pituitary Adenomas. 61
31877737 2019
38
Somatic and germline mutations in the pathogenesis of pituitary adenomas. 61
31658440 2019
39
Familial X-Linked Acrogigantism: Postnatal Outcomes and Tumor Pathology in a Prenatally Diagnosed Infant and His Mother. 61
31166600 2019
40
[Pituitary adenomas]. 61
30997549 2019
41
Germline and mosaic mutations causing pituitary tumours: genetic and molecular aspects. 61
30530903 2019
42
Mutations in GPR101 as a potential cause of X-linked acrogigantism and acromegaly. 61
30711029 2019
43
The causes and consequences of pituitary gigantism. 61
30361628 2018
44
Xq26.3 Duplication in a Boy With Motor Delay and Low Muscle Tone Refines the X-Linked Acrogigantism Genetic Locus. 61
30525125 2018
45
An update on the genetics of benign pituitary adenomas in children and adolescents. 61
30555957 2018
46
An orphan G-protein-coupled receptor causes human gigantism and/or acromegaly: Molecular biology and clinical correlations. 61
29678281 2018
47
Genomic Alterations in Sporadic Pituitary Tumors. 61
29396598 2018
48
X-Linked Acrogigantism 61
29389097 2018
49
X-LAG: How did they grow so tall? 61
28457479 2017
50
Sporadic pituitary adenomas: the role of germline mutations and recommendations for genetic screening. 61
30063429 2017

Variations for Chromosome Xq26.3 Duplication Syndrome

ClinVar genetic disease variations for Chromosome Xq26.3 Duplication Syndrome:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 overlap with 5 genes GRCh37/hg19 Xq26.3(chrX:135602028-136259908)x2 copy number gain Pathogenic 224866 GRCh37: X:135602028-136259908
GRCh38:
2 overlap with 5 genes Duplication Pathogenic 243065 GRCh37: X:135601430-136192229
GRCh38:
3 overlap with 5 genes Duplication Likely pathogenic 374410 GRCh37: X:135622314-136191699
GRCh38:
4 overlap with 7 genes Duplication Likely pathogenic 374411 GRCh37: X:135533330-136123779
GRCh38:
5 overlap with 5 genes Duplication Likely pathogenic 374412 GRCh37: X:135596446-136254970
GRCh38:
6 overlap with 7 genes Duplication Likely pathogenic 374409 GRCh37: X:135549274-136126345
GRCh38:

Expression for Chromosome Xq26.3 Duplication Syndrome

Search GEO for disease gene expression data for Chromosome Xq26.3 Duplication Syndrome.

Pathways for Chromosome Xq26.3 Duplication Syndrome

GO Terms for Chromosome Xq26.3 Duplication Syndrome

Sources for Chromosome Xq26.3 Duplication Syndrome

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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