Anophthalmos with Limb Anomalies

Categories: Eye diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Anophthalmos with Limb Anomalies

MalaCards integrated aliases for Anophthalmos with Limb Anomalies:

Name: Anophthalmos with Limb Anomalies 20 6
Waardenburg Anophthalmia Syndrome 20
Anophthalmia Waardenburg Syndrome 20
Ophthalmoacromelic Syndrome 20
Anophthalmos-Syndactyly 20


Summaries for Anophthalmos with Limb Anomalies

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1106DefinitionA rare developmental disorder characterized by bilateral microphthalmia or anophthalmia, synostosis, syndactyly, oligodactyly and/or polydactyly.EpidemiologyThe prevalence is unknown but more than 35 cases have been reported to date, mainly from consanguineous parents.Clinical descriptionThe disease presents at birth with unilateral, or more often, bilateral anophthalmia or microphthalmia and numerous limb anomalies (including synostosis, syndactyly, oligodactyly, polydactyly and long bone hypoplasia). Typically patients have clinical anophthalmia/severe microphthalmia with little/no vision. The most common limb anomalies are synostosis of the fourth and fifth metacarpals, a short 5th finger and only 4 toes bilaterally. Developmental milestones (such as responsive smile) are often delayed and most patients have moderate to severe intellectual deficiencies. Facial features can include flattened midface, sparse eyelashes, short palpebral fissures, high palate and cleft lip. Renal (horseshoe kidney), venous and vertebral anomalies have also been reported in rare cases. Early postnatal/perinatal death has occurred in several cases.EtiologyThe majority of cases are caused by mutations in the SPARC-related modular calcium binding protein 1 SMOC1 gene (14q24.1) which may be involved in the regulation of bone morphogenetic proteins. The existence of other causative genes is possible but they have not yet been discovered. The FNBP4 gene (11q12.1) was identified in a case with a phenotype similar to OAS but further studies are necessary to conclude if it is indeed causative of OAS.Diagnostic methodsDiagnosis is based on the presence of characteristic clinical findings. Computed tomography (CT) scans and magnetic resonance imaging (MRI) can also be helpful in identifying the presence or absence of the globe, optic nerve and extra ocular muscles. Identifying a mutation in the SMOC1 gene confirms diagnosis.Differential diagnosisDifferential diagnoses include isolated cryptophthalmia and other forms of syndromic microphthalmia such as microphthalmia, Lenz type, oculofaciocardiodental syndrome and anophthalmia/microphthalmia-esophageal atresia (see these terms).Antenatal diagnosisPrenatal testing via CVS or amniocentesis is possible if the causative mutation in a family has been identified. Ultrasound can also be utilized to identify the limb anomalies associated with OAS.Genetic counselingThe disease is inherited autosomal recessively so genetic counseling is possible in affected families and can help in informing parents of the recurrence risk of OAS in subsequent pregnancies. If both parents are carriers there is a 25% risk with each pregnancy of having an affected child.Management and treatmentThere is no cure for OAS. Treatment for anophthalmia/microphthalmia may be discussed with an oculoplastic surgeon and ocularist. For anophthalmia, expansion of the eyelids, socket and orbital bones is recommended as soon as possible after birth and is done via conformer therapy by an ocularist or by oculoplastic surgery using hydrogel socket expanders followed by orbital implants or dermis-fat grafts. This can help patients with achieving a more typical appearance by preventing facial deformity. Those with some vision (if the microphthalmia is not severe) may benefit from visual aids. Some limb abnormalities may also be surgically corrected to help the patient gain mobility or function, therefore orthopedic evaluation is necessary. All individuals with OAS should receive evaluation by a vision teacher and special education may be necessary.PrognosisLittle is known about the prognosis given the rarity but quality of life is usually affected due to intellectual disability, visual impairment and limb anomalies.Visit the Orphanet disease page for more resources.

MalaCards based summary : Anophthalmos with Limb Anomalies, also known as waardenburg anophthalmia syndrome, is related to microphthalmia with limb anomalies and chromosome 2q35 duplication syndrome. An important gene associated with Anophthalmos with Limb Anomalies is SMOC1 (SPARC Related Modular Calcium Binding 1).

Related Diseases for Anophthalmos with Limb Anomalies

Diseases related to Anophthalmos with Limb Anomalies via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 14)
# Related Disease Score Top Affiliating Genes
1 microphthalmia with limb anomalies 11.3
2 chromosome 2q35 duplication syndrome 10.3
3 waardenburg's syndrome 10.3
4 fryns microphthalmia syndrome 10.1
5 microphthalmia 10.1
6 synostosis 10.1
7 cleft palate, isolated 10.1
8 coloboma of macula 10.1
9 triiodothyronine receptor auxiliary protein 10.1
10 cryptorchidism, unilateral or bilateral 10.1
11 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.1
12 clubfoot 10.1
13 pierre robin syndrome 10.0
14 isolated pierre robin sequence 10.0

Graphical network of the top 20 diseases related to Anophthalmos with Limb Anomalies:

Diseases related to Anophthalmos with Limb Anomalies

Symptoms & Phenotypes for Anophthalmos with Limb Anomalies

Drugs & Therapeutics for Anophthalmos with Limb Anomalies

Search Clinical Trials , NIH Clinical Center for Anophthalmos with Limb Anomalies

Genetic Tests for Anophthalmos with Limb Anomalies

Anatomical Context for Anophthalmos with Limb Anomalies

Publications for Anophthalmos with Limb Anomalies

Articles related to Anophthalmos with Limb Anomalies:

(show all 12)
# Title Authors PMID Year
Mutations in the SPARC-related modular calcium-binding protein 1 gene, SMOC1, cause waardenburg anophthalmia syndrome. 6 61
21194680 2011
SMOC1 is essential for ocular and limb development in humans and mice. 6
21194678 2011
A locus for ophthalmo-acromelic syndrome mapped to 10p11.23. 6
19208380 2009
Correction: Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) Syndrome in Humans and Mice. 61
30586382 2018
A novel mutation in SMOC1 and variable phenotypic expression in two patients with Waardenburg anophthalmia syndrome. 61
28807869 2017
A novel homozygous variant in the SMOC1 gene underlying Waardenburg anophthalmia syndrome. 61
28085523 2017
Deletions in 14q24.1q24.3 are associated with congenital heart defects, brachydactyly, and mild intellectual disability. 61
24357125 2014
Whole-exome sequencing identified a homozygous FNBP4 mutation in a family with a condition similar to microphthalmia with limb anomalies. 61
23703728 2013
Loss of the BMP antagonist, SMOC-1, causes Ophthalmo-acromelic (Waardenburg Anophthalmia) syndrome in humans and mice. 61
21750680 2011
Anophthalmos with limb anomalies (Waardenburg opththalmo-acromelic syndrome): report of a new Italian case with renal anomaly and review. 61
17375532 2006
Waardenburg anophthalmia syndrome: report and review. 61
10607960 2000
Pulmonary alveolar microlithiasis in children. 61
8598991 1996

Variations for Anophthalmos with Limb Anomalies

ClinVar genetic disease variations for Anophthalmos with Limb Anomalies:

# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SMOC1 NM_001034852.3(SMOC1):c.718C>T (p.Gln240Ter) SNV Pathogenic 30726 rs376672665 14:70477524-70477524 14:70010807-70010807
2 SMOC1 NM_001034852.3(SMOC1):c.664+1G>A SNV Pathogenic 30727 rs863223317 14:70461198-70461198 14:69994481-69994481
3 SMOC1 NM_001034852.3(SMOC1):c.378+1G>A SNV Pathogenic 30728 rs751356341 14:70420250-70420250 14:69953533-69953533
4 SMOC1 NM_001034852.3(SMOC1):c.367T>C (p.Ser123Pro) SNV Pathogenic 427815 rs1114167455 14:70420238-70420238 14:69953521-69953521
5 SMOC1 NM_001034852.3(SMOC1):c.709G>T (p.Glu237Ter) SNV Pathogenic 562133 rs1566709754 14:70477515-70477515 14:70010798-70010798
6 SMOC1 NM_001034852.3(SMOC1):c.378+1G>T SNV Pathogenic 562135 rs751356341 14:70420250-70420250 14:69953533-69953533
7 SMOC1 NM_001034852.3(SMOC1):c.857G>A (p.Arg286His) SNV Pathogenic 562137 rs1365818420 14:70477663-70477663 14:70010946-70010946
8 SMOC1 NM_001034852.3(SMOC1):c.223C>T (p.Arg75Ter) SNV Likely pathogenic 599220 rs370866589 14:70418978-70418978 14:69952261-69952261
9 SMOC1 NM_001034852.3(SMOC1):c.812G>A (p.Cys271Tyr) SNV Likely pathogenic 562136 rs1566709825 14:70477618-70477618 14:70010901-70010901
10 SMOC1 NM_001034852.3(SMOC1):c.1223G>A (p.Cys408Tyr) SNV Likely pathogenic 562134 rs1326644602 14:70490096-70490096 14:70023379-70023379

Expression for Anophthalmos with Limb Anomalies

Search GEO for disease gene expression data for Anophthalmos with Limb Anomalies.

Pathways for Anophthalmos with Limb Anomalies

GO Terms for Anophthalmos with Limb Anomalies

Sources for Anophthalmos with Limb Anomalies

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
70 Tocris
72 UMLS via Orphanet
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