MCOPS5
MCID: MCR252
MIFTS: 32

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 57 13 72
Mcops5 57 53 59 74
Retinal Dystrophy, Early-Onset, with or Without Pituitary Dysfunction 57 74 29
Microphthalmia Syndromic 5 53 29 6
Syndromic Microphthalmia Type 5 53 59
Syndromic Microphthalmia/anophthalmia Due to Otx2 Mutation 59
Microphthalmia, Syndromic, Type 5 40
Microphthalmia, Syndromic, 5 74
Otx2-Related Eye Disorders 53
Rdeop 74

Characteristics:

Orphanet epidemiological data:

59
syndromic microphthalmia type 5
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
marked phenotypic variability in some families


HPO:

32
microphthalmia, syndromic 5:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

ICD10 via Orphanet 34 Q11.2
UMLS via Orphanet 73 C1864690
Orphanet 59 ORPHA178364
UMLS 72 C1864690

Summaries for Microphthalmia, Syndromic 5

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 178364DefinitionSyndromic 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.EpidemiologyLess than 20 cases have been reported in the literature so far.Clinical descriptionThe 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.EtiologyThe syndrome is caused by heterozygous mutations in the OTX2 gene (14q22.3).Differential diagnosisA 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 mcops5, 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

UniProtKB/Swiss-Prot : 74 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

Symptoms & Phenotypes for Microphthalmia, Syndromic 5

Human phenotypes related to Microphthalmia, Syndromic 5:

32 (show all 16)
# Description HPO Frequency HPO Source Accession
1 short stature 32 occasional (7.5%) HP:0004322
2 cleft palate 32 occasional (7.5%) HP:0000175
3 cryptorchidism 32 occasional (7.5%) HP:0000028
4 micropenis 32 occasional (7.5%) HP:0000054
5 ectopic posterior pituitary 32 occasional (7.5%) HP:0011755
6 seizures 32 HP:0001250
7 cataract 32 HP:0000518
8 global developmental delay 32 HP:0001263
9 generalized hypotonia 32 HP:0001290
10 joint laxity 32 HP:0001388
11 optic nerve hypoplasia 32 HP:0000609
12 microphthalmia 32 HP:0000568
13 anophthalmia 32 HP:0000528
14 microcornea 32 HP:0000482
15 retinal dystrophy 32 HP:0000556
16 coloboma 32 HP:0000589

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
cataract
microcornea
retinal dystrophy
coloboma
microphthalmia, unilateral or bilateral
more
Neurologic Central Nervous System:
developmental delay
hypotonia
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

Genetic Tests for Microphthalmia, Syndromic 5

Genetic tests related to Microphthalmia, Syndromic 5:

# Genetic test Affiliating Genes
1 Microphthalmia Syndromic 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:

41
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. 8 71
25293953 2014
2
Otocephaly-Dysgnathia Complex: Description of Four Cases and Confirmation of the Role of OTX2. 8 71
24167467 2013
3
OTX2 mutations contribute to the otocephaly-dysgnathia complex. 8 71
22577225 2012
4
A novel loss-of-function mutation in OTX2 in a patient with anophthalmia and isolated growth hormone deficiency. 8 71
20396904 2010
5
Heterozygous orthodenticle homeobox 2 mutations are associated with variable pituitary phenotype. 8 71
19965921 2010
6
A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction. 8 71
19956411 2009
7
OTX2 loss of function mutation causes anophthalmia and combined pituitary hormone deficiency with a small anterior and ectopic posterior pituitary. 8 71
18854396 2009
8
Novel heterozygous OTX2 mutations and whole gene deletions in anophthalmia, microphthalmia and coloboma. 8 71
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. 8 71
18628516 2008
10
Heterozygous mutations of OTX2 cause severe ocular malformations. 8 71
15846561 2005
11
Agnathia-otocephaly complex and asymmetric velopharyngeal insufficiency due to an in-frame duplication in OTX2. 8
25589041 2015
12
The genetic architecture of microphthalmia, anophthalmia and coloboma. 8
24859618 2014
13
Microphthalmia and synostotic frontal plagiocephaly: a rare clinical entity with implications for craniofacial reconstruction. 8
15988238 2005
14
Bilateral anophthalmia and esophageal atresia: report of a new patient and review of the literature. 8
15389708 2005
15
Microphthalmia/Anophthalmia/Coloboma Spectrum 71
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. 8
12543751 2003
17
Intrafamilial variability in syndromic microphthalmia type 5 caused by a novel variation in OTX2. 38
28388256 2017

Variations for Microphthalmia, Syndromic 5

ClinVar genetic disease variations for Microphthalmia, Syndromic 5:

6 (show all 15)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 OTX2 NM_172337.2(OTX2): c.402dup (p.Ser135Leufs) duplication Pathogenic rs1555350223 14:57268921-57268921 14:56802203-56802203
2 OTX2 NM_172337.3(OTX2): c.757_760del (p.Thr253fs) deletion Pathogenic rs1555350156 14:57268563-57268566 14:56801845-56801848
3 OTX2 NM_172337.3(OTX2): c.649del (p.Ala217fs) deletion Pathogenic 14:57268673-57268674 14:56801956-56801956
4 OTX2 NM_172337.3(OTX2): c.463_464dup (p.Ser156fs) duplication Pathogenic rs786205873 14:57268859-57268860 14:56802141-56802142
5 OTX2 NM_172337.3(OTX2): c.265C> G (p.Arg89Gly) single nucleotide variant Pathogenic rs104894464 14:57269058-57269058 14:56802340-56802340
6 OTX2 NM_172337.3(OTX2): c.81del (p.Ser28fs) deletion Pathogenic rs786205874 14:57272094-57272094 14:56805376-56805376
7 OTX2 NM_172337.3(OTX2): c.537T> A (p.Tyr179Ter) single nucleotide variant Pathogenic rs104894465 14:57268786-57268786 14:56802068-56802068
8 OTX2 NM_172337.3(OTX2): c.402_403CT[3] (p.Ser136fs) short repeat Pathogenic 14:57268918-57268919 14:56802200-56802201
9 OTX2 NM_172337.3(OTX2): c.413C> G (p.Ser138Ter) single nucleotide variant Pathogenic rs786205879 14:57268910-57268910 14:56802192-56802192
10 OTX2 NM_172337.3(OTX2): c.221_236del (p.Lys74fs) deletion Pathogenic 14:57270919-57270934 14:56804201-56804216
11 OTX2 NM_172337.3(OTX2): c.562G> T (p.Gly188Ter) single nucleotide variant Pathogenic rs397514463 14:57268761-57268761 14:56802043-56802043
12 OTX2 NM_172337.3(OTX2): c.270A> T (p.Arg90Ser) single nucleotide variant Pathogenic 14:57269053-57269053 14:56802335-56802335
13 OTX2 NM_172337.3(OTX2): c.292del (p.Gln98fs) deletion Pathogenic rs786205884 14:57269031-57269031 14:56802313-56802313
14 OTX2 NM_172337.3(OTX2): c.265C> T (p.Arg89Ter) single nucleotide variant Pathogenic rs104894464 14:57269058-57269058 14:56802340-56802340
15 OTX2 NM_172337.3(OTX2): c.235G> A (p.Glu79Lys) single nucleotide variant Likely pathogenic rs786205224 14:57270920-57270920 14:56804202-56804202

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

74
# 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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