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Fraser syndrome


Other Names:
Cryptophthalmos with other malformations; Cryptophthalmos-syndactyly syndrome; Cryptophthalmos syndrome; Cryptophthalmos with other malformations; Cryptophthalmos-syndactyly syndrome; Cryptophthalmos syndrome; Cyclopism; Fraser-Francois syndrome; Meyer-Schwickerath's syndrome; Ulrich-Feichtiger syndrome See More
Categories:
Fraser syndrome is a rare genetic disorder characterized by fused eyelids (cryptophthalmos), fusion of the skin between the fingers and toes (syndactyly), and abnormalities of the genitalia and urinary tract. Signs and symptoms occur early in development and may also include abnormalities of the respiratory tract, specifically involving the larynx (voice box) and trachea (windpipe); failure of kidney development affecting one or both kidneys (renal agenesis); umbilical hernia; abnormalities of the nose and ear; cleft lip and palate; skeletal abnormalities; and intellectual disability.[1][2][3] Depending on the severity of the signs and symptoms, Fraser syndrome can be fatal before or shortly after birth. Less severely affected individuals can live into childhood or adulthood.[1][3] 

Fraser syndrome is caused by mutations in three different genes: FRAS1, GRIP1, and FREM2 and is inherited in an autosomal recessive manner.[1][2] This condition is diagnosed based on signs and symptoms. Genetic testing may be useful to confirm the diagnosis.[3] While there is no cure for Fraser syndrome, there may be ways to manage symptoms, depending on the severity. A team of doctors is often needed to figure out the treatment options for each person. 
Last updated: 12/7/2016
The most common signs and symptoms of Fraser syndrome include fusion of the skin between the fingers and toes (syndactyly), fusion of the eyelids (cryptophthalmos), and abnormalities of the urinary and airway tract.[3] Other symptoms may include:[1][2][3]
  • Eyes: Small eyes (microphthalmia), missing eyes (anophthalmia), absent or malformed lacrimal (tear) ducts, increased distance between the eyes (hypertelorism), vision loss
  • Face: Unusual hairline, missing eyebrows and/or eyelashes 
  • Ears: Malformations of ear structure, hearing loss 
  • Nose: Small, abnormally shaped nostrils, flattening of the top part of the nose (low nasal bridge) 
  • Mouth: Cleft lip and palate, tooth crowding
  • Respiratory: Abnormal development of the voicebox (larynx) and trachea (windpipe), respiratory insufficiency 
  • Chest and abdomen: Widely spaced nipples and umbilical abnormalities (umbilical hernia)
  • Genitourinary: Ambiguous genitalia, hypospadias (abnormal urethral opening in the penis), cryptorchidism (undescended testicle), absent or abnormal kidneys (renal agenesis or hypoplasia)
  • Skeletal: Separation of the pubic bones (diastasis of symphysis pubis), scoliosis, missing ribs
  • Neurologic: Small head size (microcephaly), spina bifida, intellectual disability
Last updated: 12/7/2016

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
Blindness 0000618
Cryptophthalmos 0001126
Finger syndactyly 0006101
Lacrimal duct aplasia
Absent tear duct
0007925
Malformed lacrimal duct
Malformed tear ducts
0007993
Multicystic kidney dysplasia 0000003
Renal hypoplasia
Small kidneys
Underdeveloped kidneys
[ more ] 		0000089
30%-79% of people have these symptoms
Ambiguous genitalia
Ambiguous external genitalia
Ambiguous external genitalia at birth
Intersex genitalia
[ more ] 		0000062
Anal atresia
Absent anus
0002023
Anal stenosis
Narrowing of anal opening
0002025
Anophthalmia
Absence of eyeballs
Failure of development of eyeball
Missing eyeball
No eyeball
[ more ] 		0000528
Bifid tongue
Cleft tongue
Forked tongue
Split tongue
[ more ] 		0010297
Dental crowding
Crowded teeth
Dental overcrowding
Overcrowding of teeth
[ more ] 		0000678
Dental malocclusion
Bad bite
Malalignment of upper and lower dental arches
Misalignment of upper and lower dental arches
[ more ] 		0000689
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
External ear malformation 0008572
Female pseudohermaphroditism 0010458
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ] 		0000316
Hypoplasia of penis
Underdeveloped penis
0008736
Laryngeal stenosis 0001602
Low-set, posteriorly rotated ears 0000368
Microphthalmia
Abnormally small eyeball
0000568
Scrotal hypoplasia
Smaller than typical growth of scrotum
0000046
Toe syndactyly
Fused toes
Webbed toes
[ more ] 		0001770
Vaginal atresia
Abnormally closed or absent vagina
0000148
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge
[ more ] 		0000431
Wide pubic symphysis 0003183
5%-29% of people have these symptoms
Abnormal hair pattern
Abnormal distribution of hair
0010720
Abnormal lung lobation 0002101
Abnormality of cardiovascular system morphology 0030680
Atresia of the external auditory canal
Absent ear canal
0000413
Bicornuate uterus
Heart shaped uterus
Heart-shaped uterus
[ more ] 		0000813
Calvarial skull defect
Cranial defect
Skull defect
[ more ] 		0001362
Cleft ala nasi
Cleft nostril
0003191
Cleft upper lip
Harelip
0000204
Conductive hearing impairment
Conductive deafness
Conductive hearing loss
[ more ] 		0000405
Cryptorchidism
Undescended testes
Undescended testis
[ more ] 		0000028
Death in infancy
Infantile death
Lethal in infancy
[ more ] 		0001522
Ectopic anus
Abnormal anus position
0004397
Encephalocele 0002084
High palate
Elevated palate
Increased palatal height
[ more ] 		0000218
Hypospadias 0000047
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Midline nasal groove
Central nasal groove
0004112
Myelomeningocele 0002475
Omphalocele 0001539
Pulmonary hypoplasia
Small lung
Underdeveloped lung
[ more ] 		0002089
Subglottic stenosis 0001607
Tracheal stenosis
Narrowing of windpipe
0002777
Umbilical hernia 0001537
Underdeveloped nasal alae
Underdeveloped tissue around nostril
0000430
Urethral atresia 0000068
Vertebral segmentation defect 0003422
Wide intermamillary distance
Wide-spaced nipples
Widely spaced nipples
Widely-spaced nipples
[ more ] 		0006610
Percent of people who have these symptoms is not available through HPO
Abnormal cortical gyration 0002536
Abnormal heart morphology
Abnormality of the heart
Abnormally shaped heart
Heart defect
[ more ] 		0001627
Abnormal umbilicus morphology
Abnormal belly button
Abnormal navel
[ more ] 		0001551
Abnormality of the anus 0004378
Abnormality of the pinna
Abnormally shaped ears
Auricular malformation
Deformed ears
Malformed ears
[ more ] 		0000377
Abnormality of the small intestine 0002244
Abnormality of the thymus 0000777
Absent eyebrow
Failure of development of eyebrows
0002223
Absent eyelashes
Failure of development of eyelashes
0000561
Aplasia/Hypoplasia of the phalanges of the hand 0009767
Aplasia/Hypoplasia of the sternum
Absent/small sternum
Absent/underdeveloped sternum
[ more ] 		0006714
Aplasia/Hypoplasia of the thumb
Absent/small thumb
Absent/underdeveloped thumb
[ more ] 		0009601
Autosomal recessive inheritance 0000007
Bilateral microphthalmos
Abnormally small eyeball on both sides
0007633
Choanal stenosis
Narrowing of the rear opening of the nasal cavity
0000452
Cleft palate
Cleft roof of mouth
0000175
Clitoral hypertrophy
Enlarged clitoris
0008665
Corneal opacity 0007957
Cupped ear
Cup-shaped ears
Simple, cup-shaped ears
[ more ] 		0000378
Cutaneous finger syndactyly
Webbed fingers
Webbed skin of fingers
[ more ] 		0010554
Difficulty in tongue movements 0000183
Extension of hair growth on temples to lateral eyebrow 0005325
Facial cleft
Cleft of the face
0002006
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hypoplastic superior helix 0008559
Laryngeal atresia 0008750
Laryngeal web 0005950
Low-set ears
Low set ears
Lowset ears
[ more ] 		0000369
Micropenis
Short penis
Small penis
[ more ] 		0000054
Morphological abnormality of the middle ear
Middle ear malformation
0008609
Renal hypoplasia/aplasia
Absent/small kidney
Absent/underdeveloped kidney
[ more ] 		0008678
Severe T-cell immunodeficiency 0005352
Upper eyelid coloboma
Cleft upper eyelid
Notched upper eyelid
[ more ] 		0000636
Wide nose
Broad nose
Increased breadth of nose
Increased nasal breadth
Increased nasal width
Increased width of nose
[ more ] 		0000445
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Last updated: 7/1/2020
Fraser syndrome is a genetic (inherited) disorder. It is caused by mutations in three different genes: FRAS1, GRIP1, and FREM2. The FRAS1 and FREM2 genes codes for proteins that work together and are involved in the proper development of the skin, internal organs, and other tissues. The GRIP1 gene codes for the GRIP1 protein, which ensures that the FRAS1 and FREM2 proteins get to the correct location of the cell to work together. Mutations in these genes are thought to impair the ability of the FRAS1 and FREM2 proteins, resulting in abnormal development of certain organs and tissues before birth.[1]
Last updated: 12/7/2016
Fraser syndrome is inherited in an autosomal recessive manner.[1] This means that to be affected, a person must have a mutation in both copies of one of the three responsible genes (FRAS1, GRIP1, or FREM2) in each cell. Individuals with Fraser syndrome inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected) and often do not know they are carriers until they have an affected child. When 2 carriers of an autosomal recessive condition have children, each child has a:
  • 25% chance to be affected
  • 50% chance to be an unaffected carrier like each parent
  • 25% chance to be unaffected and not a carrier
Last updated: 12/7/2016
Fraser syndrome is diagnosed based on the signs and symptoms found in each individual. Many different researchers have proposed diagnostic guidelines based on a certain number of symptoms considered to be major (or common) criteria and a certain number of symptoms considered to be minor (or less common) criteria. Although there is some debate regarding what is classified as major versus minor criteria, most researchers agree that a diagnosis is made based on the finding of 3 major criteria, or 2 major and 2 minor criteria, or 1 major and 3 minor criteria.[2][3][4]

Genetic testing may additionally be useful to confirm the diagnosis. 
Last updated: 12/7/2016

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.
At this time, there is no cure for Fraser syndrome. Treatment varies depending on the severity of symptoms present in each individual. Some malformations may be corrected with surgery.[5] A team of specialists is needed to evaluate each individual and determine what methods can be used to manage or treat each symptom.  
Last updated: 12/7/2016
The long-term outlook (prognosis) for Fraser syndrome differs depending on the severity of the signs and symptoms present. Fraser syndrome can be fatal before or shortly after birth in approximately 40% of cases. Abnormalities of the central nervous system, larynx (voice box) and pharynx (windpipe); absent or underdeveloped kidneys; and respiratory insufficiency may lead to a poor prognosis. In the absence of these findings, individuals may have a normal life span.[6][7]
Last updated: 12/7/2016
Approximately 250 cases of Fraser syndrome have been reported throughout the world. It is estimated that Fraser syndrome occurs in about 1 out of 500,000 individuals in Europe (including those that pass away before or shortly after birth).[3][4] It is possible that there are more individuals with Fraser syndrome who have not been diagnosed, given the similarity of symptoms to other conditions and the potential for more mild cases. 
Last updated: 12/7/2016

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

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Fraser syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

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 Fraser syndrome. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

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 Fraser syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Fraser syndrome. Genetics Home Reference. June 2014; https://ghr.nlm.nih.gov/condition/fraser-syndrome. Accessed 12/7/2016.
  2. McKusick, VA. Fraser syndrome. OMIM. 10/05/2015; http://www.omim.org/entry/219000. Accessed 12/7/2016.
  3. Tessier, A. et al. Fraser syndrome: Features suggestive of prenatal diagnosis in a review of 38 cases.. Prenatal Diagnosis. November 17, 2016; https://www.ncbi.nlm.nih.gov/pubmed/27859469.
  4. De Bernardo, G. et al. Prenatal diagnosis of Fraser syndrome: a matter of life or death?. Italian Journal of Pediatrics. November 2015; 9(41):https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640198/.
  5. Fraser Syndrome. NORD. 2006; https://rarediseases.org/rare-diseases/fraser-syndrome/. Accessed 12/8/2016.
  6. Fraser syndrome. Orphanet. March 2006; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2052. Accessed 12/7/2016.
  7. Mario Impallomeni, Deepak Subramanian, Nazim Mahmood, Illes Joseph. Fraser syndrome in a 96-year-old female. Age and Ageing. Nov 2006; 35(6):642-543. http://ageing.oxfordjournals.org/content/35/6/642.full.