MCOPS5
MCID: MCR252
MIFTS: 34

Microphthalmia, Syndromic 5 (MCOPS5)

Categories: Cardiovascular diseases, Ear diseases, Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Oral diseases, Rare diseases, Reproductive diseases, Respiratory diseases

Aliases & Classifications for Microphthalmia, Syndromic 5

MalaCards integrated aliases for Microphthalmia, Syndromic 5:

Name: Microphthalmia, Syndromic 5 56 13 43 71
Syndromic Microphthalmia Type 5 12 52 58 29 6
Mcops5 56 12 52 58 73
Retinal Dystrophy, Early-Onset, with or Without Pituitary Dysfunction 56 73 29
Syndromic Microphthalmia/anophthalmia Due to Otx2 Mutation 12 58
Microphthalmia, Syndromic, Type 5 39
Microphthalmia, Syndromic, 5 73
Syndromic Microphthalmia 5 12
Microphthalmia Syndromic 5 52
Otx2-Related Eye Disorders 52
Rdeop 73

Characteristics:

Orphanet epidemiological data:

58
syndromic microphthalmia type 5
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
marked phenotypic variability in some families


HPO:

31
microphthalmia, syndromic 5:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare eye diseases
Developmental anomalies during embryogenesis


Summaries for Microphthalmia, Syndromic 5

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 178364 Definition Syndromic microphthalmia, type 5 is characterized by the association of a range of ocular anomalies (anophthalmia, microphthalmia and retinal abnormalities) with variable developmental delay and central nervous system malformations. Epidemiology Less than 20 cases have been reported in the literature so far. Clinical description The clinical picture is highly variable, even between affected members of the same family. Ocular findings ranged from bilateral anophthalmia, to severe or mild bi- or unilateral microphthalmia and retinal dystrophy. MRI may reveal optic nerve aplasia/hypoplasia, hippocampal malformations, structural abnormalities of the pituitary gland, and agenesis of the corpus callosum . Severe developmental delay was noted in some patients, whilst others showed normal cognitive development. Pituitary dysfunction, leading to growth hormone deficiency and short stature , or combined pituitary hormone deficiency (CPHD), has also been reported. Etiology The syndrome is caused by heterozygous mutations in the OTX2 gene (14q22.3). Differential diagnosis A similar phenotype with bilateral anophthalmia and pituitary abnormalities (with additional findings of limb defects, ear anomalies and facial dysmorphism) is found in patients carrying a deletion encompassing the OTX2 gene. Patients with the full clinical spectrum of ocular anomalies, central nervous system abnormalities and pituitary abnormalities also show significant overlap with septooptic dysplasia (see this term). Visit the Orphanet disease page for more resources.

MalaCards based summary : Microphthalmia, Syndromic 5, also known as syndromic microphthalmia type 5, is related to coloboma of macula and fryns microphthalmia syndrome. An important gene associated with Microphthalmia, Syndromic 5 is OTX2 (Orthodenticle Homeobox 2). Affiliated tissues include pituitary and eye, and related phenotypes are short stature and cleft palate

Disease Ontology : 12 A syndromic microphthalmia characterized by unilateral or bilateral microphthalmia or clinical anophthalmia and variable additional features that has material basis in heterozygous mutation in OTX2 on chromosome 14q22.3.

UniProtKB/Swiss-Prot : 73 Microphthalmia, syndromic, 5: Patients manifest unilateral or bilateral microphthalmia/clinical anophthalmia and variable additional features including pituitary dysfunction, coloboma, microcornea, cataract, retinal dystrophy, hypoplasia or agenesis of the optic nerve, agenesis of the corpus callosum, developmental delay, joint laxity, hypotonia, and seizures. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities.
Retinal dystrophy, early-onset, with or without pituitary dysfunction: An autosomal dominant ocular disease characterized by pattern dystrophy of the retinal pigment epithelium, and photoreceptor degeneration. Mild developmental anomalies include optic nerve head dysplasia, microcornea, and Rathke's cleft cyst. Some patients manifest pituitary dysfunction.

More information from OMIM: 610125 PS309800

Related Diseases for Microphthalmia, Syndromic 5

Graphical network of the top 20 diseases related to Microphthalmia, Syndromic 5:



Diseases related to Microphthalmia, Syndromic 5

Symptoms & Phenotypes for Microphthalmia, Syndromic 5

Human phenotypes related to Microphthalmia, Syndromic 5:

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 short stature 31 occasional (7.5%) HP:0004322
2 cleft palate 31 occasional (7.5%) HP:0000175
3 cryptorchidism 31 occasional (7.5%) HP:0000028
4 micropenis 31 occasional (7.5%) HP:0000054
5 ectopic posterior pituitary 31 occasional (7.5%) HP:0011755
6 cataract 31 HP:0000518
7 global developmental delay 31 HP:0001263
8 joint laxity 31 HP:0001388
9 anophthalmia 31 HP:0000528
10 microphthalmia 31 HP:0000568
11 microcornea 31 HP:0000482
12 retinal dystrophy 31 HP:0000556
13 generalized hypotonia 31 HP:0001290
14 coloboma 31 HP:0000589
15 optic nerve hypoplasia 31 HP:0000609
16 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
cataract
microcornea
retinal dystrophy
coloboma
microphthalmia, unilateral or bilateral
more
Neurologic Central Nervous System:
hypotonia
developmental delay
seizures (rare)
corpus callosum, agenesis of (in some patients)
pituitary hypoplasia (in some patients)
more
Growth Height:
short stature (in some patients)

Genitourinary Internal Genitalia Male:
cryptorchidism (rare)

Skeletal:
joint laxity

Head And Neck Mouth:
cleft palate (in some patients)
dysgnathia or agnathnia (in some patients)

Genitourinary External Genitalia Male:
small penis (rare)

Endocrine Features:
pituitary hypoplasia (in some patients)
pituitary hormone deficiencies (in some patients)

Clinical features from OMIM:

610125

Drugs & Therapeutics for Microphthalmia, Syndromic 5

Search Clinical Trials , NIH Clinical Center for Microphthalmia, Syndromic 5

Cochrane evidence based reviews: microphthalmia, syndromic 5

Genetic Tests for Microphthalmia, Syndromic 5

Genetic tests related to Microphthalmia, Syndromic 5:

# Genetic test Affiliating Genes
1 Syndromic Microphthalmia Type 5 29 OTX2
2 Retinal Dystrophy, Early-Onset, with or Without Pituitary Dysfunction 29

Anatomical Context for Microphthalmia, Syndromic 5

MalaCards organs/tissues related to Microphthalmia, Syndromic 5:

40
Pituitary, Eye

Publications for Microphthalmia, Syndromic 5

Articles related to Microphthalmia, Syndromic 5:

(show all 17)
# Title Authors PMID Year
1
OTX2 mutations cause autosomal dominant pattern dystrophy of the retinal pigment epithelium. 6 56
25293953 2014
2
Otocephaly-Dysgnathia Complex: Description of Four Cases and Confirmation of the Role of OTX2. 56 6
24167467 2013
3
OTX2 mutations contribute to the otocephaly-dysgnathia complex. 56 6
22577225 2012
4
A novel loss-of-function mutation in OTX2 in a patient with anophthalmia and isolated growth hormone deficiency. 6 56
20396904 2010
5
Heterozygous orthodenticle homeobox 2 mutations are associated with variable pituitary phenotype. 56 6
19965921 2010
6
A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction. 56 6
19956411 2009
7
OTX2 loss of function mutation causes anophthalmia and combined pituitary hormone deficiency with a small anterior and ectopic posterior pituitary. 56 6
18854396 2009
8
Novel heterozygous OTX2 mutations and whole gene deletions in anophthalmia, microphthalmia and coloboma. 6 56
18781617 2008
9
OTX2 mutation in a patient with anophthalmia, short stature, and partial growth hormone deficiency: functional studies using the IRBP, HESX1, and POU1F1 promoters. 6 56
18628516 2008
10
Heterozygous mutations of OTX2 cause severe ocular malformations. 6 56
15846561 2005
11
Agnathia-otocephaly complex and asymmetric velopharyngeal insufficiency due to an in-frame duplication in OTX2. 56
25589041 2015
12
The genetic architecture of microphthalmia, anophthalmia and coloboma. 56
24859618 2014
13
Microphthalmia and synostotic frontal plagiocephaly: a rare clinical entity with implications for craniofacial reconstruction. 56
15988238 2005
14
Bilateral anophthalmia and esophageal atresia: report of a new patient and review of the literature. 56
15389708 2005
15
Microphthalmia/Anophthalmia/Coloboma Spectrum – ARCHIVED CHAPTER, FOR HISTORICAL REFERENCE ONLY 6
20301552 2004
16
A clinical and molecular genetic study of a rare dominantly inherited syndrome (MRCS) comprising of microcornea, rod-cone dystrophy, cataract, and posterior staphyloma. 56
12543751 2003
17
Intrafamilial variability in syndromic microphthalmia type 5 caused by a novel variation in OTX2. 61
28388256 2017

Variations for Microphthalmia, Syndromic 5

ClinVar genetic disease variations for Microphthalmia, Syndromic 5:

6 (show all 39) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 OTX2 NM_021728.4(OTX2):c.811del (p.Thr271fs)deletion Pathogenic 812111 14:57268536-57268536 14:56801818-56801818
2 OTX2 NM_021728.4(OTX2):c.487_488dup (p.Ser164fs)duplication Pathogenic 9515 rs786205873 14:57268858-57268859 14:56802140-56802141
3 OTX2 NM_021728.4(OTX2):c.289C>G (p.Arg97Gly)SNV Pathogenic 9516 rs104894464 14:57269058-57269058 14:56802340-56802340
4 OTX2 NM_021728.4(OTX2):c.81del (p.Ser28fs)deletion Pathogenic 9517 rs786205874 14:57272094-57272094 14:56805376-56805376
5 OTX2 NM_021728.4(OTX2):c.561T>A (p.Tyr187Ter)SNV Pathogenic 9518 rs104894465 14:57268786-57268786 14:56802068-56802068
6 OTX2 NM_021728.4(OTX2):c.426_427CT[3] (p.Ser144fs)short repeat Pathogenic 30024 rs1566623121 14:57268917-57268918 14:56802199-56802200
7 OTX2 NM_021728.4(OTX2):c.437C>G (p.Ser146Ter)SNV Pathogenic 30025 rs786205879 14:57268910-57268910 14:56802192-56802192
8 OTX2 NM_021728.4(OTX2):c.245_260del (p.Lys82fs)deletion Pathogenic 30026 rs1566624472 14:57270919-57270934 14:56804201-56804216
9 OTX2 NM_021728.4(OTX2):c.586G>T (p.Gly196Ter)SNV Pathogenic 30027 rs397514463 14:57268761-57268761 14:56802043-56802043
10 OTX2 NM_021728.4(OTX2):c.294A>T (p.Arg98Ser)SNV Pathogenic 30028 rs1566623392 14:57269053-57269053 14:56802335-56802335
11 OTX2 NM_021728.4(OTX2):c.316del (p.Gln106fs)deletion Pathogenic 190249 rs786205884 14:57269031-57269031 14:56802313-56802313
12 OTX2 NM_021728.4(OTX2):c.289C>T (p.Arg97Ter)SNV Pathogenic 190250 rs104894464 14:57269058-57269058 14:56802340-56802340
13 OTX2 NM_172337.2(OTX2):c.402dup (p.Ser135Leufs)duplication Pathogenic 500507 rs1555350223 14:57268920-57268921 14:56802202-56802203
14 OTX2 NM_021728.4(OTX2):c.781_784del (p.Thr261fs)deletion Pathogenic 545433 rs1555350156 14:57268563-57268566 14:56801845-56801848
15 OTX2 NM_021728.4(OTX2):c.673del (p.Ala225fs)deletion Pathogenic 561071 rs1566622571 14:57268674-57268674 14:56801956-56801956
16 OTX2 NM_021728.4(OTX2):c.749del (p.Gly250fs)deletion Pathogenic 666555 14:57268598-57268598 14:56801880-56801880
17 OTX2 NM_021728.4(OTX2):c.259G>A (p.Glu87Lys)SNV Likely pathogenic 190251 rs786205224 14:57270920-57270920 14:56804202-56804202
18 OTX2 NM_021728.4(OTX2):c.641C>A (p.Thr214Asn)SNV Conflicting interpretations of pathogenicity 288894 rs150982073 14:57268706-57268706 14:56801988-56801988
19 OTX2 NM_021728.4(OTX2):c.*933C>TSNV Uncertain significance 313408 rs886050555 14:57267520-57267520 14:56800802-56800802
20 OTX2 NM_021728.4(OTX2):c.*764G>ASNV Uncertain significance 313410 rs775857186 14:57267689-57267689 14:56800971-56800971
21 OTX2 NM_021728.4(OTX2):c.*647A>GSNV Uncertain significance 313412 rs886050557 14:57267806-57267806 14:56801088-56801088
22 OTX2 NM_021728.4(OTX2):c.425C>G (p.Pro142Arg)SNV Uncertain significance 803030 14:57268922-57268922 14:56802204-56802204
23 OTX2 NM_021728.4(OTX2):c.*219G>ASNV Uncertain significance 313416 rs886050559 14:57268234-57268234 14:56801516-56801516
24 OTX2 NM_021728.4(OTX2):c.380G>C (p.Arg127Pro)SNV Uncertain significance 313419 rs199799627 14:57268967-57268967 14:56802249-56802249
25 OTX2 NM_021728.4(OTX2):c.*648C>GSNV Uncertain significance 313411 rs886050556 14:57267805-57267805 14:56801087-56801087
26 OTX2 NM_021728.4(OTX2):c.380G>T (p.Arg127Leu)SNV Uncertain significance 313418 rs199799627 14:57268967-57268967 14:56802249-56802249
27 OTX2 NM_021728.4(OTX2):c.-119-65G>TSNV Uncertain significance 313424 rs886050561 14:57272358-57272358 14:56805640-56805640
28 OTX2 NM_021728.4(OTX2):c.*1018T>CSNV Uncertain significance 881431 14:57267435-57267435 14:56800717-56800717
29 OTX2 NM_021728.4(OTX2):c.*993G>CSNV Uncertain significance 881432 14:57267460-57267460 14:56800742-56800742
30 OTX2 NM_021728.4(OTX2):c.*667A>CSNV Uncertain significance 881870 14:57267786-57267786 14:56801068-56801068
31 OTX2 NM_021728.4(OTX2):c.*648C>ASNV Uncertain significance 883039 14:57267805-57267805 14:56801087-56801087
32 OTX2 NM_021728.4(OTX2):c.*543A>GSNV Uncertain significance 883040 14:57267910-57267910 14:56801192-56801192
33 OTX2 NM_021728.4(OTX2):c.*147G>TSNV Uncertain significance 883822 14:57268306-57268306 14:56801588-56801588
34 OTX2 NM_021728.4(OTX2):c.713A>T (p.His238Leu)SNV Uncertain significance 881494 14:57268634-57268634 14:56801916-56801916
35 OTX2 NM_021728.4(OTX2):c.96G>T (p.Pro32=)SNV Uncertain significance 880601 14:57272079-57272079 14:56805361-56805361
36 OTX2 NM_021728.4(OTX2):c.*10G>ASNV Benign/Likely benign 288866 rs171978 14:57268443-57268443 14:56801725-56801725
37 OTX2 NM_021728.4(OTX2):c.*779G>ASNV Benign/Likely benign 313409 rs138197536 14:57267674-57267674 14:56800956-56800956
38 OTX2 NM_021728.4(OTX2):c.97+12C>TSNV Benign/Likely benign 313422 rs28757218 14:57272066-57272066 14:56805348-56805348
39 OTX2 NM_021728.4(OTX2):c.459C>T (p.Ser153=)SNV Benign/Likely benign 313417 rs34537598 14:57268888-57268888 14:56802170-56802170

UniProtKB/Swiss-Prot genetic disease variations for Microphthalmia, Syndromic 5:

73
# Symbol AA change Variation ID SNP ID
1 OTX2 p.Arg89Gly VAR_029354 rs104894464
2 OTX2 p.Pro133Thr VAR_029355 rs376333965
3 OTX2 p.Pro134Ala VAR_029356 rs753783256
4 OTX2 p.Arg90Ser VAR_065952
5 OTX2 p.Glu79Lys VAR_073793 rs786205224

Expression for Microphthalmia, Syndromic 5

Search GEO for disease gene expression data for Microphthalmia, Syndromic 5.

Pathways for Microphthalmia, Syndromic 5

GO Terms for Microphthalmia, Syndromic 5

Sources for Microphthalmia, Syndromic 5

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