MOTA
MCID: MNT006
MIFTS: 35

Manitoba Oculotrichoanal Syndrome (MOTA)

Categories: Eye diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Rare diseases, Smell/Taste diseases

Aliases & Classifications for Manitoba Oculotrichoanal Syndrome

MalaCards integrated aliases for Manitoba Oculotrichoanal Syndrome:

Name: Manitoba Oculotrichoanal Syndrome 57 20 43 58 73 36 13 39
Marles Syndrome 57 20 43 58 73
Oculotrichoanal Syndrome 20 58 29 6
Marles-Greenberg-Persaud Syndrome 20 43 58
Mota 57 43 73
Marles Greenberg Persaud Syndrome 43 71
Mota Syndrome 20 58
Unilateral Upper Eyelid Coloboma, Aberrant Anterior Hairline Pattern, and Anal Anomalies 20
Manitoba Trichoanal Syndrome 20

Characteristics:

Orphanet epidemiological data:

58
oculotrichoanal syndrome
Inheritance: Autosomal recessive;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive

Miscellaneous:
majority of cases in manitoba indians, northeastern manitoba, canada


HPO:

31
manitoba oculotrichoanal syndrome:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare eye diseases
Developmental anomalies during embryogenesis


External Ids:

OMIM® 57 248450
KEGG 36 H00686
MeSH 44 D005124
ICD10 via Orphanet 33 Q87.8
UMLS via Orphanet 72 C1855425
Orphanet 58 ORPHA2717
MedGen 41 C1855425
UMLS 71 C1855425

Summaries for Manitoba Oculotrichoanal Syndrome

MedlinePlus Genetics : 43 Manitoba oculotrichoanal syndrome is a condition involving several characteristic physical features, particularly affecting the eyes (oculo-), hair (tricho-), and anus (-anal).People with Manitoba oculotrichoanal syndrome have widely spaced eyes (hypertelorism). They may also have other eye abnormalities including small eyes (microphthalmia), a notched or partially absent upper eyelid (upper eyelid coloboma), eyelids that are attached to the front surface of the eye (corneopalpebral synechiae), or eyes that are completely covered by skin and usually malformed (cryptophthalmos). These abnormalities may affect one or both eyes.Individuals with Manitoba oculotrichoanal syndrome usually have abnormalities of the front hairline, such as hair growth extending from the temple to the eye on one or both sides of the face. One or both eyebrows may be completely or partially missing. Most people with this disorder also have a wide nose with a notched tip; in some cases this notch extends up from the tip so that the nose appears to be divided into two halves (bifid nose).About 20 percent of people with Manitoba oculotrichoanal syndrome have defects in the abdominal wall, such as a soft out-pouching around the belly-button (an umbilical hernia) or an opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel. Another characteristic feature of Manitoba oculotrichoanal syndrome is a narrow anus (anal stenosis) or an anal opening farther forward than usual. Umbilical wall defects or anal malformations may require surgical correction. Some affected individuals also have malformations of the kidneys.The severity of the features of Manitoba oculotrichoanal syndrome may vary even within the same family. With appropriate treatment, affected individuals generally have normal growth and development, intelligence, and life expectancy.

MalaCards based summary : Manitoba Oculotrichoanal Syndrome, also known as marles syndrome, is related to hypertelorism and fraser syndrome 1. An important gene associated with Manitoba Oculotrichoanal Syndrome is FREM1 (FRAS1 Related Extracellular Matrix 1). Affiliated tissues include eye, and related phenotypes are hypertelorism and abnormal hair pattern

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 2717DefinitionOculotrichoanal syndrome is a form of rare, multiple congenital anomalies/dysmorphic syndrome characterized by a combination of various nose, eye, gastrointestinal and genitourinary abnormalities. Clinical presentation is variable and often includes bifid and broad nasal tip, aberrant anterior hairline, coloboma, cryptophthalmos or unilateral anophthalmia, anal anomalies, and omphalocele. Intelligence and global development is normal.Visit the Orphanet disease page for more resources.

OMIM® : 57 Manitoba-oculo-tricho-anal (MOTA) syndrome is a rare condition defined by eyelid colobomas, cryptophthalmos, and anophthalmia/microphthalmia, an aberrant hairline, a bifid or broad nasal tip, and gastrointestinal anomalies such as omphalocele and anal stenosis. Autosomal recessive inheritance was assumed because of consanguinity in the Oji-Cre population of Manitoba in which the syndrome was first described (summary by Slavotinek et al., 2011). (248450) (Updated 05-Mar-2021)

KEGG : 36 Manitoba oculotrichoanal (MOTA) syndrome is a rare condition characterized by aberrant anterior hairline, upper-eyelid colobomas, hypertelorism, cryptophthalmos, a bifid or notched nose, and anal anomalies. MOTA syndrome is inherited in an autosomal recessive manner.

UniProtKB/Swiss-Prot : 73 Manitoba oculotrichoanal syndrome: A rare condition defined by eyelid colobomas, cryptophthalmos, and anophthalmia/microphthalmia, an aberrant hairline, a bifid or broad nasal tip, and gastrointestinal anomalies such as omphalocele and anal stenosis.

Related Diseases for Manitoba Oculotrichoanal Syndrome

Diseases related to Manitoba Oculotrichoanal Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 19)
# Related Disease Score Top Affiliating Genes
1 hypertelorism 10.2
2 fraser syndrome 1 10.2
3 frem1 autosomal recessive disorders 10.2
4 autosomal recessive disease 10.1
5 cryptophthalmos 10.1
6 coloboma of macula 10.0
7 renal hypodysplasia/aplasia 1 10.0
8 fryns microphthalmia syndrome 10.0
9 bifid nose with or without anorectal and renal anomalies 10.0
10 helix syndrome 10.0
11 omphalocele 10.0
12 bifid nose 10.0
13 chromosome 2q35 duplication syndrome 9.9
14 telecanthus 9.9
15 encephalopathy, progressive, with or without lipodystrophy 9.9
16 partial cryptophthalmia 9.9
17 microphthalmia 9.9
18 vaginal atresia 9.9
19 renal dysplasia 9.9

Graphical network of the top 20 diseases related to Manitoba Oculotrichoanal Syndrome:



Diseases related to Manitoba Oculotrichoanal Syndrome

Symptoms & Phenotypes for Manitoba Oculotrichoanal Syndrome

Human phenotypes related to Manitoba Oculotrichoanal Syndrome:

58 31 (show all 13)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000316
2 abnormal hair pattern 58 31 hallmark (90%) Very frequent (99-80%) HP:0010720
3 upper eyelid coloboma 58 31 hallmark (90%) Very frequent (99-80%) HP:0000636
4 nasolacrimal duct obstruction 58 31 frequent (33%) Frequent (79-30%) HP:0000579
5 anteriorly placed anus 58 31 frequent (33%) Frequent (79-30%) HP:0001545
6 anal stenosis 58 31 frequent (33%) Frequent (79-30%) HP:0002025
7 anophthalmia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000528
8 microphthalmia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000568
9 cryptophthalmos 58 31 occasional (7.5%) Occasional (29-5%) HP:0001126
10 bifid nasal tip 58 31 occasional (7.5%) Occasional (29-5%) HP:0000456
11 omphalocele 31 HP:0001539
12 abnormal hair morphology 31 HP:0001595
13 eyelid coloboma 31 HP:0000625

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Head And Neck Eyes:
hypertelorism
nasolacrimal duct obstruction
eyelid coloboma
anophthalmia, clinical
oculopalpebral synechia
more
Head And Neck Nose:
nasal tip groove

Abdomen Gastrointestinal:
omphalocele
anal stenosis
anteriorly displaced anus

Skin Nails Hair Hair:
aberrant anterolateral scalp hairline

Clinical features from OMIM®:

248450 (Updated 05-Mar-2021)

Drugs & Therapeutics for Manitoba Oculotrichoanal Syndrome

Search Clinical Trials , NIH Clinical Center for Manitoba Oculotrichoanal Syndrome

Genetic Tests for Manitoba Oculotrichoanal Syndrome

Genetic tests related to Manitoba Oculotrichoanal Syndrome:

# Genetic test Affiliating Genes
1 Oculotrichoanal Syndrome 29 FREM1

Anatomical Context for Manitoba Oculotrichoanal Syndrome

MalaCards organs/tissues related to Manitoba Oculotrichoanal Syndrome:

40
Eye

Publications for Manitoba Oculotrichoanal Syndrome

Articles related to Manitoba Oculotrichoanal Syndrome:

# Title Authors PMID Year
1
Manitoba-oculo-tricho-anal (MOTA) syndrome is caused by mutations in FREM1. 57 6
21507892 2011
2
Manitoba Oculotrichoanal (MOTA) syndrome: report of eight new cases. 57 6
17352387 2007
3
Micro-ablepharon of the upper eyelids and vaginal atresia. 6 57
11332973 2001
4
Familial upper eyelid coloboma with ipsilateral anterior hairline abnormality: two new reports of MOTA syndrome. 61 57
19291776 2009
5
Mutation analysis of the FRAS1 gene demonstrates new mutations in a propositus with Fraser syndrome. 57 61
16894541 2006
6
New familial syndrome of unilateral upper eyelid coloboma, aberrant anterior hairline pattern, and anal anomalies in Manitoba Indians. 57
1554017 1992
7
Anatomical classification facial, cranio-facial and latero-facial clefts. 57
820824 1976
8
A homozygous mutation p.Arg2167Trp in FREM2 causes isolated cryptophthalmos. 61
29688405 2018
9
A wedge-shaped anterior hairline extension associated with a tessier number 10 cleft. 61
23197915 2012
10
Evidence for additional FREM1 heterogeneity in Manitoba oculotrichoanal syndrome. 61
22690109 2012

Variations for Manitoba Oculotrichoanal Syndrome

ClinVar genetic disease variations for Manitoba Oculotrichoanal Syndrome:

6 (show top 50) (show all 285)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FREM1 NG_017005.2:g.64585_124811del Deletion Pathogenic 30762 9:14790424-14850650 9:14790426-14850652
2 FREM1 NM_144966.5(FREM1):c.2097_2100del (p.Lys699fs) Deletion Pathogenic 30763 rs769407804 9:14824092-14824095 9:14824094-14824097
3 FREM1 FREM1, VAL209ILE Variation Pathogenic 30765
4 FREM1 NM_144966.5(FREM1):c.3971T>G (p.Leu1324Arg) SNV Likely pathogenic 30764 rs281875281 9:14792751-14792751 9:14792753-14792753
5 FREM1 NM_144966.5(FREM1):c.1493G>A (p.Arg498Gln) SNV Conflicting interpretations of pathogenicity 30767 rs184394424 9:14842559-14842559 9:14842561-14842561
6 FREM1 NC_000009.12:g.14736170A>T SNV Uncertain significance 912594 9:14736168-14736168 9:14736170-14736170
7 FREM1 NC_000009.12:g.14736181C>T SNV Uncertain significance 912595 9:14736179-14736179 9:14736181-14736181
8 FREM1 NC_000009.12:g.14736345G>T SNV Uncertain significance 912596 9:14736343-14736343 9:14736345-14736345
9 FREM1 NC_000009.12:g.14736355T>G SNV Uncertain significance 912597 9:14736353-14736353 9:14736355-14736355
10 FREM1 NC_000009.12:g.14737573A>G SNV Uncertain significance 912639 9:14737571-14737571 9:14737573-14737573
11 FREM1 NC_000009.12:g.14740191G>A SNV Uncertain significance 912640 9:14740189-14740189 9:14740191-14740191
12 FREM1 NC_000009.12:g.14740203T>C SNV Uncertain significance 912641 9:14740201-14740201 9:14740203-14740203
13 FREM1 NM_144966.5(FREM1):c.*1258G>A SNV Uncertain significance 366078 rs886063757 9:14736136-14736136 9:14736138-14736138
14 FREM1 NM_144966.5(FREM1):c.8C>T (p.Ser3Phe) SNV Uncertain significance 366179 rs201217735 9:14868968-14868968 9:14868970-14868970
15 FREM1 NM_144966.5(FREM1):c.3872C>G (p.Thr1291Ser) SNV Uncertain significance 366127 rs574640129 9:14792850-14792850 9:14792852-14792852
16 FREM1 NM_144966.5(FREM1):c.578C>G (p.Pro193Arg) SNV Uncertain significance 425454 rs377565472 9:14859234-14859234 9:14859236-14859236
17 FREM1 NM_144966.5(FREM1):c.2887_2888CA[2] (p.Thr964fs) Microsatellite Uncertain significance 631547 rs777983437 9:14812811-14812812 9:14812813-14812814
18 FREM1 NM_144966.5(FREM1):c.6258C>T (p.Tyr2086=) SNV Uncertain significance 730988 rs187325866 9:14740229-14740229 9:14740231-14740231
19 FREM1 NM_144966.5(FREM1):c.6231G>T (p.Ala2077=) SNV Uncertain significance 715848 rs148735553 9:14746374-14746374 9:14746376-14746376
20 FREM1 NC_000009.12:g.14769856T>C SNV Uncertain significance 912680 9:14769854-14769854 9:14769856-14769856
21 FREM1 NM_144966.5(FREM1):c.4945A>G (p.Ile1649Val) SNV Uncertain significance 729685 rs199891537 9:14770717-14770717 9:14770719-14770719
22 FREM1 NC_000009.12:g.14789027C>T SNV Uncertain significance 912721 9:14789025-14789025 9:14789027-14789027
23 FREM1 NC_000009.12:g.14789041C>G SNV Uncertain significance 912722 9:14789039-14789039 9:14789041-14789041
24 FREM1 NC_000009.12:g.14789073G>C SNV Uncertain significance 912723 9:14789071-14789071 9:14789073-14789073
25 FREM1 NC_000009.12:g.14789094A>G SNV Uncertain significance 912724 9:14789092-14789092 9:14789094-14789094
26 FREM1 NC_000009.12:g.14792849C>A SNV Uncertain significance 912725 9:14792847-14792847 9:14792849-14792849
27 FREM1 NC_000009.12:g.14808132C>T SNV Uncertain significance 912774 9:14808130-14808130 9:14808132-14808132
28 FREM1 NC_000009.12:g.14812866C>A SNV Uncertain significance 912775 9:14812864-14812864 9:14812866-14812866
29 FREM1 NC_000009.12:g.14812917T>C SNV Uncertain significance 912776 9:14812915-14812915 9:14812917-14812917
30 FREM1 NC_000009.12:g.14824957C>T SNV Uncertain significance 912818 9:14824955-14824955 9:14824957-14824957
31 FREM1 NC_000009.12:g.14841447C>T SNV Uncertain significance 912819 9:14841445-14841445 9:14841447-14841447
32 FREM1 NC_000009.12:g.14841450T>C SNV Uncertain significance 912820 9:14841448-14841448 9:14841450-14841450
33 FREM1 NM_001370060.1(FREM1):c.-194G>A SNV Uncertain significance 912907 9:14869169-14869169 9:14869171-14869171
34 FREM1 NM_001370060.1(FREM1):c.-265T>C SNV Uncertain significance 912908 9:14869240-14869240 9:14869242-14869242
35 FREM1 NM_001370060.1(FREM1):c.-395C>T SNV Uncertain significance 912909 9:14910039-14910039 9:14910041-14910041
36 FREM1 NM_001370060.1(FREM1):c.-476G>T SNV Uncertain significance 912910 9:14910120-14910120 9:14910122-14910122
37 FREM1 NM_001370060.1(FREM1):c.-491C>T SNV Uncertain significance 912911 9:14910135-14910135 9:14910137-14910137
38 FREM1 NM_144966.5(FREM1):c.3874C>T (p.Arg1292Cys) SNV Uncertain significance 708381 rs199806592 9:14792848-14792848 9:14792850-14792850
39 FREM1 NC_000009.12:g.14797524A>T SNV Uncertain significance 913086 9:14797522-14797522 9:14797524-14797524
40 FREM1 NC_000009.12:g.14813057G>C SNV Uncertain significance 913132 9:14813055-14813055 9:14813057-14813057
41 FREM1 NC_000009.12:g.14816771T>C SNV Uncertain significance 913133 9:14816769-14816769 9:14816771-14816771
42 FREM1 NC_000009.12:g.14816775C>T SNV Uncertain significance 913134 9:14816773-14816773 9:14816775-14816775
43 FREM1 NC_000009.12:g.14819276C>T SNV Uncertain significance 913135 9:14819274-14819274 9:14819276-14819276
44 FREM1 NC_000009.12:g.14842638G>A SNV Uncertain significance 913185 9:14842636-14842636 9:14842638-14842638
45 FREM1 NC_000009.12:g.14842657C>T SNV Uncertain significance 913186 9:14842655-14842655 9:14842657-14842657
46 FREM1 NC_000009.12:g.14842675A>G SNV Uncertain significance 913187 9:14842673-14842673 9:14842675-14842675
47 FREM1 NM_001370060.1(FREM1):c.544C>G (p.Leu182Val) SNV Uncertain significance 913237 9:14859268-14859268 9:14859270-14859270
48 FREM1 NM_001370060.1(FREM1):c.517G>A (p.Val173Ile) SNV Uncertain significance 913238 9:14859295-14859295 9:14859297-14859297
49 FREM1 NM_001370060.1(FREM1):c.329+10A>C SNV Uncertain significance 913239 9:14863797-14863797 9:14863799-14863799
50 FREM1 NM_001370060.1(FREM1):c.329+7G>A SNV Uncertain significance 913240 9:14863800-14863800 9:14863802-14863802

UniProtKB/Swiss-Prot genetic disease variations for Manitoba Oculotrichoanal Syndrome:

73
# Symbol AA change Variation ID SNP ID
1 FREM1 p.Leu1324Arg VAR_066412 rs281875281
2 FREM1 p.Val2091Ile VAR_066413 rs281875282

Expression for Manitoba Oculotrichoanal Syndrome

Search GEO for disease gene expression data for Manitoba Oculotrichoanal Syndrome.

Pathways for Manitoba Oculotrichoanal Syndrome

GO Terms for Manitoba Oculotrichoanal Syndrome

Sources for Manitoba Oculotrichoanal 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 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....