What are the other Names for this Condition? (Also known as/Synonyms)

• Anophthalmia, Cleft Lip/Palate, Facial Anomalies, and CNS Anomalies and Hypothalamic Disorder
• Fryns Anophthalmia Syndrome
• Microphthalmia with Facial Clefting

What is Anophthalmia Plus Syndrome? (Definition/Background Information)

• Anophthalmia Plus Syndrome (APS) is a very rare syndrome that involves malformations in multiple organs of the body
• The most common findings in affected individuals are anophthalmia (absence of one or both eyes) or severe microphthalmia (abnormally small eyes), and cleft lip and/or cleft palate
• Other findings may include wide-set eyes (hypertelorism); low-set ears; narrowed or blocked nasal passages (choanal stenosis or atresia); sacral neural tube defect, midline abdominal wall defects, clinodactyly, eye colobomas and congenital glaucoma
• It has been suggested that Anophthalmia Plus Syndrome is inherited in an autosomal recessive manner, although the genetic cause has not yet been identified

(Source: Anophthalmia Plus Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Anophthalmia Plus Syndrome? (Age and Sex Distribution)

• Anophthalmia Plus Syndrome is a very rare congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Anophthalmia Plus Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Anophthalmia Plus Syndrome can be inherited
• Currently, no other risk factors have been clearly identified for APS

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Anophthalmia Plus Syndrome? (Etiology)

• It has been suggested that Anophthalmia Plus Syndrome is inherited in an autosomal recessive manner, although the genetic cause has not yet been identified

(Source: Anophthalmia Plus Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

What are the Signs and Symptoms of Anophthalmia Plus Syndrome?

Anophthalmia Plus Syndrome (APS) may involve malformations in multiple organs of the body including the eyes, ears, nose, face, mouth, brain, sacral vertebrae, meninges (tissue that lines the outer part of the brain and spinal cord), abdominal wall, heart, digits (fingers and toes), and endocrine system.

Based on the few cases reported in the literature, it appears that all affected individuals have had anophthalmia (absence of one or both eyes) and/or microphthalmia (abnormally small eyes). It has also been estimated that approximately 89% of affected individuals have had an oral-facial cleft (such as cleft lip and/or cleft palate).

Other specific findings that have been reported in more than one affected individual include wide-set eyes (hypertelorism), low-set ears, choanal stenosis or atresia (narrowing or blockage of the nasal passages), sacral neural tube defect, midline abdominal wall defects, clinodactyly (abnormally bent or curved finger), eye colobomas, and congenital glaucoma. There have been other, additional abnormalities that have only been reported in single individuals.

In general, the signs and symptoms of Anophthalmia Plus Syndrome may include:

• Abnormality of the genitourinary system
• Abnormality of the vertebral column
• Macrotia
• Microphthalmia

Based on the frequency of symptoms observed, the following information may be noted:

Very frequently present symptoms in 80-99% of the cases: Anophthalmia

Frequently present symptoms in 30-79% of the cases:

• Abnormal nasal morphology 
• Bilateral cleft lip and palate 
• Choanal atresia 
• Facial cleft 
• Hypertelorism
• Low-set, posteriorly rotated ears

Occasionally present symptoms in 5-29% of the cases:

• Aplasia/hypoplasia of the earlobes
• Blepharophimosis
• Cleft eyelid 
• Deviation of finger 
• Iris coloboma 
• Spina bifida
• Vertebral segmentation defect

(Source: Anophthalmia Plus Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Anophthalmia Plus Syndrome Diagnosed?

Anophthalmia Plus Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Anophthalmia Plus Syndrome?

The complications of Anophthalmia Plus Syndrome may include:

• Severe visual impairment
• Neurological abnormalities
• Physical deformities
• Reduced quality of life

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Anophthalmia Plus Syndrome Treated?

Presently, there is no cure for Anophthalmia Plus Syndrome, since it may be a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develops.

How can Anophthalmia Plus Syndrome be Prevented?

Currently, Anophthalmia Plus Syndrome may not be preventable, since it is reportedly a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Anophthalmia Plus Syndrome? (Outcomes/Resolutions)

• The prognosis of Anophthalmia Plus Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Anophthalmia Plus Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/