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Disease Profile

Anophthalmos with limb anomalies

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Neonatal

ICD-10

Q87.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Anophthalmia Waardenburg syndrome; Waardenburg anophthalmia syndrome; Anophthalmos-syndactyly;

Categories

Congenital and Genetic Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 1106

Definition
A rare developmental disorder characterized by bilateral microphthalmia or anophthalmia, synostosis, syndactyly, oligodactyly and/or polydactyly.

Epidemiology
The prevalence is unknown but more than 35 cases have been reported to date, mainly from consanguineous parents.

Clinical description
The 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.

Etiology
The 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 methods
Diagnosis 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 diagnosis
Differential 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 diagnosis
Prenatal 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 counseling
The 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 treatment
There 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.

Prognosis
Little 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.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal eyebrow morphology
Abnormality of the eyebrow
0000534
Abnormality of the metacarpal bones
Abnormality of the long bone of hand
0001163
Blepharophimosis
Narrow opening between the eyelids
0000581
Finger syndactyly
0006101
Frontal bossing
0002007
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion

[ more ]

0000327
Microphthalmia
Abnormally small eyeball
0000568
Prominent forehead
Pronounced forehead
Protruding forehead

[ more ]

0011220
Sandal gap
Gap between 1st and 2nd toes
Gap between first and second toe
Increased space between first and second toes
Sandal gap between first and second toes
Wide space between 1st, 2nd toes
Wide space between first and second toes
Wide-spaced big toe
Widely spaced 1st-2nd toes
Widely spaced first and second toes
Widened gap 1st-2nd toes
Widened gap first and second toe

[ more ]

0001852
Synostosis of carpal bones
Fusion of wrist bones
0005048
Toe syndactyly
Fused toes
Webbed toes

[ more ]

0001770
True anophthalmia
Completely missing eyeball
0011478
30%-79% of people have these symptoms
Abnormal form of the vertebral bodies
0003312
Bilateral single transverse palmar creases
0007598
Camptodactyly of 2nd-5th fingers
0001215
Cleft upper lip
Harelip
0000204
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Fibular hypoplasia
Short calf bone
0003038
Foot oligodactyly
Missing toes
0001849
Hand oligodactyly
Hand has less than 5 fingers
0001180
Intellectual disability, moderate
IQ between 34 and 49
0002342
Intellectual disability, severe
Early and severe mental retardation
Mental retardation, severe
Severe mental retardation

[ more ]

0010864
Large earlobe
Fleshy earlobe
Fleshy earlobes
Prominent ear lobes
prominent ear lobules

[ more ]

0009748
Low-set, posteriorly rotated ears
0000368
Optic atrophy
0000648
Postaxial hand polydactyly
Extra little finger
Extra pinkie finger
Extra pinky finger

[ more ]

0001162
Short stature
Decreased body height
Small stature

[ more ]

0004322
Short tibia
Short shinbone
Short skankbone

[ more ]

0005736
Tarsal synostosis
Fused ankle bones
0008368
Tibial bowing
Bowed shankbone
Bowed shinbone

[ more ]

0002982
5%-29% of people have these symptoms
Arrhinencephaly
0002139
Broad thumb
Broad thumbs
Wide/broad thumb

[ more ]

0011304
Cleft palate
Cleft roof of mouth
0000175
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Death in infancy
Infantile death
Lethal in infancy

[ more ]

0001522
Elbow dislocation
Dislocations of the elbows
Elbow dislocations

[ more ]

0003042
High palate
Elevated palate
Increased palatal height

[ more ]

0000218
Hip dislocation
Dislocated hips
Dislocation of hip

[ more ]

0002827
Horseshoe kidney
Horseshoe kidneys
0000085
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hypoplasia of the premaxilla
Hypoplasia of the primary palate bone
Premaxillary bone deficiency
Primary palate bone deficiency
Small premaxilla
Small primary palate bone
Underdevelopment of the premaxilla
Underdevelopment of the primary palate bone

[ more ]

0010650
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Long philtrum
0000343
Macrodontia
Increased width of tooth
0001572
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Postaxial foot polydactyly
Extra toe attached near the little toe
0001830
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot

[ more ]

0001762
Thin vermilion border
Decreased volume of lip
Thin lips

[ more ]

0000233
Venous insufficiency
Poorly functioning veins
0005293
Percent of people who have these symptoms is not available through HPO
Abnormal hair morphology
Abnormality of the hair
Hair abnormality

[ more ]

0001595
Abnormality of the cardiovascular system
Cardiovascular abnormality
0001626
Anophthalmia

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Anophthalmos with limb anomalies. This website is maintained by the National Library of Medicine.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Anophthalmos with limb anomalies. Click on the link to view a sample search on this topic.

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