MCID: INT324
MIFTS: 46

Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies

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

Aliases & Classifications for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal...

MalaCards integrated aliases for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies:

Name: Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies 53 71 28 69
Image Syndrome 53 12 23 49 55 71 13 14
Intrauterine Growth Retardation-Metaphyseal Dysplasia-Adrenal Hypoplasia Congenita-Genital Anomalies Syndrome 49 55
Intrauterine Growth Restriction 23 28
Intrauterine Growth Restriction, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, Genital Abnormalities 12
Adrenal Hypoplasia Congenita,genital Anomalies 23
Pyle Metaphyseal Dysplasia 69
Fetal Growth Retardation 69
Metaphyseal Dysplasia 23
Image 71

Characteristics:

Orphanet epidemiological data:

55
image syndrome
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal dominant


HPO:

31
intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies:
Inheritance autosomal dominant inheritance


GeneReviews:

23
Penetrance Although few large pedigrees with image syndrome have been reported to date, it is clear that the mode of inheritance is autosomal dominant in which only maternal transmission of the imprinted pathogenic variant results in image syndrome [arboleda et al 2012]...

Classifications:



Summaries for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal...

NIH Rare Diseases : 49 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 85173Disease definitionIMAGe syndrome is characterized by the association of Intrauterine growth retardation, Metaphyseal dysplasia (and short limbs), Adrenal hypoplasia congenita, and Genital anomalies. It has been described in less than 20 cases. The patients also present with dysmorphic features (frontal bossing, broad nasal bridge, low-set ears). In boys, genital anomalies include bilateral cryptorchidism, hypospadias, micropenis, and hypogonadotropic hypogonadism. This syndrome is likely to be transmitted as an autosomal recessivetrait.Visit the Orphanet disease page for more resources. Last updated: 1/22/2007

MalaCards based summary : Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies, also known as image syndrome, is related to pyle disease and spondylo-megaepiphyseal-metaphyseal dysplasia, and has symptoms including low-set ears, frontal bossing and muscular hypotonia. An important gene associated with Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies is CDKN1C (Cyclin Dependent Kinase Inhibitor 1C), and among its related pathways/superpathways are Glucose / Energy Metabolism and Corticotropin-releasing hormone signaling pathway. Affiliated tissues include bone, and related phenotypes are Increased shRNA abundance (Z-score > 2) and Increased shRNA abundance (Z-score > 2)

Disease Ontology : 12 A syndrome that is characterized by intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, genital abnormalities and has physical basis in heterozygous mutation in the CDKN1C gene.

OMIM : 53 IMAGE syndrome is a rare multisystem disorder characterized by intrauterine growth restriction, metaphyseal dysplasia, congenital adrenal hypoplasia, and genital anomalies. Patients with this condition may present shortly after birth with severe adrenal insufficiency, which can be life-threatening if not recognized early and steroid replacement therapy commenced. Other reported features in this condition include hypercalciuria and/or hypocalcemia, craniosynostosis, cleft palate, and scoliosis (summary by Balasubramanian et al., 2010). (614732)

UniProtKB/Swiss-Prot : 71 Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies: A rare condition characterized by intrauterine growth restriction, metaphyseal dysplasia, congenital adrenal hypoplasia, and genital anomalies. Patients with this condition may present shortly after birth with severe adrenal insufficiency, which can be life-threatening if not recognized early and commenced on steroid replacement therapy. Other reported features in this condition include, hypercalciuria and/or hypercalcemia, craniosynostosis, cleft palate, and scoliosis.

GeneReviews: NBK190103

Related Diseases for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal...

Diseases related to Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 28)
# Related Disease Score Top Affiliating Genes
1 pyle disease 31.0 CDKN1C NR0B1
2 spondylo-megaepiphyseal-metaphyseal dysplasia 12.4
3 metaphyseal dysplasia, spahr type 12.4
4 osteosclerotic metaphyseal dysplasia 12.3
5 clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly 12.3
6 metaphyseal dysplasia maxillary hypoplasia brachydactyly 12.3
7 intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies 12.0
8 laurin-sandrow syndrome 11.7
9 chromosome xp21 deletion syndrome 10.4 GK NR0B1
10 gestational trophoblastic neoplasm 10.3 CDKN1C NR0B1
11 hemihyperplasia, isolated 10.3 CDKN1C KCNQ1OT1
12 adrenal hypoplasia, congenital 10.2 GK NR0B1 STAR
13 spastic paraplegia 17, autosomal dominant 10.1 CDKN1C KCNQ1OT1 TGM1
14 achalasia-addisonianism-alacrima syndrome 10.0 NNT POMC
15 46 xy gonadal dysgenesis 10.0 CYP11A1 NR0B1 STAR
16 acute adrenal insufficiency 9.9 CYP11A1 POMC
17 premature ovarian failure 1 9.9 CYP11A1 LHX8 STAR
18 adrenocortical carcinoma, hereditary 9.9 CDKN1C CYP11A1 NR0B1 STAR
19 cholesterol ester storage disease 9.9 CYP11A1 STAR
20 testicular leydig cell tumor 9.7 CYP11A1 POMC STAR
21 adrenal cortical hypofunction 9.7 CYP11A1 GK NR0B1 POMC
22 steroid inherited metabolic disorder 9.7 CYP11A1 POMC STAR
23 lipoid congenital adrenal hyperplasia 9.7 CYP11A1 POMC STAR
24 familial glucocorticoid deficiency 9.6 NNT NR0B1 POMC STAR TXNRD2
25 hypoadrenocorticism, familial 9.6 CYP11A1 NR0B1 POMC STAR
26 adrenal carcinoma 9.6 CYP11A1 NR0B1 POMC STAR
27 neurodermatitis 9.5 DECR1 POMC
28 adrenal insufficiency, congenital, with 46,xy sex reversal, partial or complete 9.4 CYP11A1 NNT POMC SGPL1 STAR

Graphical network of the top 20 diseases related to Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies:



Diseases related to Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies

Symptoms & Phenotypes for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal...

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Ears:
low-set ears

Head And Neck Face:
prominent forehead

Genitourinary Internal Genitalia Male:
cryptorchidism

Laboratory Abnormalities:
hypercalciuria
hypercalcemia

Endocrine Features:
growth hormone deficiency
adrenal hypoplasia, congenital
adrenal crisis in neonatal period

Genitourinary Internal Genitalia Female:
normal

Neurologic Central Nervous System:
developmental delay (in some patients)

Head And Neck Nose:
short nose
flat nasal bridge

Skeletal:
epiphyseal dysplasia
metaphyseal dysplasia
delayed bone age

Growth:
intrauterine growth retardation
postnatal growth failure

Genitourinary External Genitalia Male:
hypospadias
micropenis

Genitourinary External Genitalia Female:
normal

Head And Neck Head:
macrocephaly (in some patients)

Genitourinary Kidneys:
renal calcification (in some patients)


Clinical features from OMIM:

614732

Human phenotypes related to Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies:

55 31 (show all 24)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 low-set ears 55 31 hallmark (90%) Very frequent (99-80%) HP:0000369
2 frontal bossing 55 31 hallmark (90%) Very frequent (99-80%) HP:0002007
3 muscular hypotonia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001252
4 depressed nasal bridge 55 31 hallmark (90%) Very frequent (99-80%) HP:0005280
5 micromelia 55 31 hallmark (90%) Very frequent (99-80%) HP:0002983
6 cryptorchidism 55 31 hallmark (90%) Very frequent (99-80%) HP:0000028
7 intrauterine growth retardation 55 31 hallmark (90%) Very frequent (99-80%) HP:0001511
8 hypogonadism 55 31 hallmark (90%) Very frequent (99-80%) HP:0000135
9 hypospadias 55 31 hallmark (90%) Very frequent (99-80%) HP:0000047
10 hydronephrosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0000126
11 adrenal hypoplasia 55 31 hallmark (90%) Very frequent (99-80%) HP:0000835
12 metaphyseal dysplasia 55 31 hallmark (90%) Very frequent (99-80%) HP:0100255
13 macrocephaly 31 occasional (7.5%) HP:0000256
14 global developmental delay 31 occasional (7.5%) HP:0001263
15 delayed skeletal maturation 31 HP:0002750
16 short nose 31 HP:0003196
17 prominent forehead 31 HP:0011220
18 epiphyseal dysplasia 31 HP:0002656
19 postnatal growth retardation 31 HP:0008897
20 hypercalciuria 31 HP:0002150
21 hypercalcemia 31 HP:0003072
22 abnormality of the genital system 55 Very frequent (99-80%)
23 micropenis 31 HP:0000054
24 growth hormone deficiency 31 HP:0000824

GenomeRNAi Phenotypes related to Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies according to GeneCards Suite gene sharing:

25 (show all 23)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-106 9.77 MCM4
2 Increased shRNA abundance (Z-score > 2) GR00366-A-122 9.77 PRDM16
3 Increased shRNA abundance (Z-score > 2) GR00366-A-126 9.77 PRDM16
4 Increased shRNA abundance (Z-score > 2) GR00366-A-128 9.77 DECR1 MCM4
5 Increased shRNA abundance (Z-score > 2) GR00366-A-146 9.77 LHX8
6 Increased shRNA abundance (Z-score > 2) GR00366-A-149 9.77 LHX8
7 Increased shRNA abundance (Z-score > 2) GR00366-A-151 9.77 DECR1
8 Increased shRNA abundance (Z-score > 2) GR00366-A-164 9.77 MCM4
9 Increased shRNA abundance (Z-score > 2) GR00366-A-168 9.77 PRDM16 DECR1 LHX8 MCM4
10 Increased shRNA abundance (Z-score > 2) GR00366-A-185 9.77 PRDM16
11 Increased shRNA abundance (Z-score > 2) GR00366-A-192 9.77 MCM4
12 Increased shRNA abundance (Z-score > 2) GR00366-A-199 9.77 MCM4
13 Increased shRNA abundance (Z-score > 2) GR00366-A-21 9.77 MCM4
14 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.77 DECR1 LHX8
15 Increased shRNA abundance (Z-score > 2) GR00366-A-23 9.77 LHX8
16 Increased shRNA abundance (Z-score > 2) GR00366-A-45 9.77 MCM4
17 Increased shRNA abundance (Z-score > 2) GR00366-A-46 9.77 MCM4
18 Increased shRNA abundance (Z-score > 2) GR00366-A-5 9.77 MCM4
19 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.77 MCM4
20 Increased shRNA abundance (Z-score > 2) GR00366-A-67 9.77 DECR1
21 Increased shRNA abundance (Z-score > 2) GR00366-A-76 9.77 MCM4
22 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.77 DECR1
23 Increased shRNA abundance (Z-score > 2) GR00366-A-96 9.77 MCM4

MGI Mouse Phenotypes related to Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.85 CYP11A1 LHX6 LHX8 LTB4R MCM4 POMC
2 endocrine/exocrine gland MP:0005379 9.56 NR0B1 POMC PRDM16 SGPL1 STAR TSPO
3 homeostasis/metabolism MP:0005376 9.4 CYP11A1 DECR1 LHX6 LTB4R NR0B1 POMC

Drugs & Therapeutics for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal...

Search Clinical Trials , NIH Clinical Center for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies

Genetic Tests for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal...

Genetic tests related to Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies:

# Genetic test Affiliating Genes
1 Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies 28 CDKN1C
2 Intrauterine Growth Restriction 28

Anatomical Context for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal...

MalaCards organs/tissues related to Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies:

38
Bone

Publications for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal...

Articles related to Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies:

# Title Authors Year
1
Is Hyperpigmentation on the First Day of Life Always Associated with IMAGe Syndrome? ( 25541901 )
2014
2
Anesthetic and dental management of a child with IMAGe syndrome. ( 25517553 )
2014
3
IMAGe syndrome: clinical and genetic implications based on investigations in three Japanese patients. ( 24313804 )
2013
4
Increased protein stability of CDKN1C causes a gain-of-function phenotype in patients with IMAGe syndrome. ( 24098681 )
2013
5
Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome. ( 22634751 )
2012
6
IMAGe syndrome: Case report with a previously unreported feature and review of published literature. ( 21108398 )
2010
7
Two sisters with IMAGe syndrome: cytomegalic adrenal histopathology, support for autosomal recessive inheritance and literature review. ( 16835919 )
2006
8
IMAGe syndrome: a complex disorder affecting growth, adrenal and gonadal function, and skeletal development. ( 14760276 )
2004
9
IMAGe, a new clinical association of intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies. ( 10599684 )
1999
10
IMAGe Syndrome ( 24624461 )
1993

Variations for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal...

UniProtKB/Swiss-Prot genetic disease variations for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies:

71
# Symbol AA change Variation ID SNP ID
1 CDKN1C p.Asp274Asn VAR_068848 rs387907225
2 CDKN1C p.Phe276Ser VAR_068849 rs387907224
3 CDKN1C p.Phe276Val VAR_068850 rs387907223
4 CDKN1C p.Lys278Glu VAR_068851 rs387907226
5 CDKN1C p.Arg279Pro VAR_068852 rs318240750

ClinVar genetic disease variations for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 CDKN1C NM_000076.2(CDKN1C): c.826T> G (p.Phe276Val) single nucleotide variant Pathogenic rs387907223 GRCh37 Chromosome 11, 2905359: 2905359
2 CDKN1C NM_000076.2(CDKN1C): c.827T> C (p.Phe276Ser) single nucleotide variant Pathogenic rs387907224 GRCh37 Chromosome 11, 2905358: 2905358
3 CDKN1C NM_000076.2(CDKN1C): c.836G> C (p.Arg279Pro) single nucleotide variant Pathogenic rs318240750 GRCh37 Chromosome 11, 2905349: 2905349
4 CDKN1C NM_000076.2(CDKN1C): c.820G> A (p.Asp274Asn) single nucleotide variant Pathogenic rs387907225 GRCh37 Chromosome 11, 2905900: 2905900
5 CDKN1C NM_000076.2(CDKN1C): c.832A> G (p.Lys278Glu) single nucleotide variant Pathogenic rs387907226 GRCh37 Chromosome 11, 2905353: 2905353
6 CDKN1C NM_000076.2(CDKN1C): c.815T> G (p.Ile272Ser) single nucleotide variant Pathogenic rs515726203 GRCh38 Chromosome 11, 2884675: 2884675
7 CDKN1C NM_000076.2(CDKN1C): c.836G> T (p.Arg279Leu) single nucleotide variant Pathogenic rs318240750 GRCh38 Chromosome 11, 2884119: 2884119
8 CDKN1C NM_000076.2(CDKN1C): c.842G> T (p.Arg281Ile) single nucleotide variant Pathogenic rs886037912 GRCh38 Chromosome 11, 2884113: 2884113

Expression for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal...

Search GEO for disease gene expression data for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies.

Pathways for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal...

Pathways related to Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.94 CYP11A1 STAR TSPO TXNRD2
2 11.1 CYP11A1 POMC STAR
3
Show member pathways
10.74 CYP11A1 POMC STAR

GO Terms for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal...

Cellular components related to Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.17 CYP11A1 DECR1 GK NNT STAR TSPO

Biological processes related to Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 female gonad development GO:0008585 9.4 LHX8 SGPL1
2 cholesterol transport GO:0030301 9.37 STAR TSPO
3 adrenal gland development GO:0030325 9.32 NR0B1 TSPO
4 Leydig cell differentiation GO:0033327 9.26 NR0B1 SGPL1
5 steroid biosynthetic process GO:0006694 9.26 CYP11A1 NR0B1 STAR TSPO
6 regulation of steroid biosynthetic process GO:0050810 9.16 STAR TSPO
7 C21-steroid hormone biosynthetic process GO:0006700 8.8 CYP11A1 STAR TSPO

Molecular functions related to Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cholesterol transporter activity GO:0017127 8.62 STAR TSPO

Sources for Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
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47 NDF-RT
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51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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