National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Anophthalmia plus syndrome


Other Names:
Fryns microphthalmia syndrome; Fryns anophthalmia syndrome; Microphthalmia with facial clefting; Fryns microphthalmia syndrome; Fryns anophthalmia syndrome; Microphthalmia with facial clefting; Anophthalmia, cleft lip/palate, facial anomalies, and CNS anomalies and hypothalamic disorder; Leichtman Wood Rohn syndrome See More
Categories:
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 APS is inherited in an autosomal recessive manner, although the genetic cause has not yet been identified.[1]
Last updated: 11/17/2011
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.[1]
Last updated: 11/18/2011

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.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Anophthalmia
Absence of eyeballs
Failure of development of eyeball
Missing eyeball
No eyeball
[ more ] 		0000528
30%-79% of people have these symptoms
Abnormal nasal morphology
Abnormal of nasal shape
Abnormal of shape of nose
[ more ] 		0005105
Bilateral cleft lip and palate
Right and left cleft lip and palate
0002744
Choanal atresia
Blockage of the rear opening of the nasal cavity
Obstruction of the rear opening of the nasal cavity
[ more ] 		0000453
Facial cleft
Cleft of the face
0002006
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ] 		0000316
Low-set, posteriorly rotated ears 0000368
5%-29% of people have these symptoms
Aplasia/Hypoplasia of the earlobes
Absent/small ear lobes
Absent/underdeveloped ear lobes
[ more ] 		0009906
Blepharophimosis
Narrow opening between the eyelids
0000581
Deviation of finger
Atypical position of finger
Finger pointing in a different direction than usual
[ more ] 		0004097
Eyelid coloboma
Cleft eyelid
Notched eyelid
[ more ] 		0000625
Iris coloboma
Cat eye
0000612
Spina bifida 0002414
Vertebral segmentation defect 0003422
Percent of people who have these symptoms is not available through HPO
Abnormality of the ear 0000598
Abnormality of the genitourinary system 0000119
Abnormality of the vertebral column
Abnormal spine
Abnormal vertebral column
Abnormality of the spine
[ more ] 		0000925
Autosomal recessive inheritance 0000007
Macrotia
Large ears
0000400
Microphthalmia
Abnormally small eyeball
0000568
Neural tube defect 0045005
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Last updated: 7/1/2020
A review of the available medical literature does not currently yield information about specific diagnostic criteria for anophthalmia plus syndrome (APS). Because APS is so rarely reported, specific diagnostic criteria may not exist. Anophthalmia and/or microphthalmia with oral-facial clefting occurs in a number of known syndromes; however, the other known syndromes typically have specific other features (such as limb abnormalities, deafness or other organ anomalies).[2] A diagnosis of APS may be considered when an individual has the signs and symptoms most commonly reported in affected individuals, but other known syndromes with overlapping features have been ruled out.
Last updated: 11/18/2011

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

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

  • The National Eye Institute (NEI) provides more information on anophthalmia and microphthalmia in general. The NEI was created to conduct research, distribute health information, and support other programs that protect and prolong the vision of Americans. Click on the above link to view information on this topic.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions. Click on the link to view an article providing an overview of anophthalmia and microphthalmia in general.
  • 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 Anophthalmia plus syndrome. Click on the link to view a sample search on this topic.

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  1. Makhoul IR, Soudack M, Kochavi O, Guilburd JN, Maimon S, Gershoni-Baruch R. Anophthalmia-plus syndrome: A clinical report and review of the literature. Am J Med Genet. 2007; 143(A):64-68.
  2. Wiltshire, Esko; Moore, Mark; Casey, Theresa; Smith, Greg; Smith, Scott; Thompson, Elizabeth. Fryns ‘Anophthalmia-Plus’ syndrome associated with developmental regression. Clinical Dysmorphology. January 2003; 12(1):41-43.