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Disease Profile

Fraser syndrome

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.


US Estimated

Europe Estimated

Age of onset





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


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.


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.


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


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.


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.


Not applicable


Other names (AKA)

Cryptophthalmos with other malformations; Cryptophthalmos-syndactyly syndrome; Cryptophthalmos syndrome;


Congenital and Genetic Diseases; Digestive Diseases; Ear, Nose, and Throat Diseases;


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.


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

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:
80%-99% of people have these symptoms
Finger syndactyly
Lacrimal duct aplasia
Absent tear duct
Malformed lacrimal duct
Malformed tear ducts
Multicystic kidney dysplasia
Renal hypoplasia
Small kidneys
Underdeveloped kidneys

[ more ]

30%-79% of people have these symptoms
Ambiguous genitalia
Ambiguous external genitalia
Ambiguous external genitalia at birth
Intersex genitalia

[ more ]

Anal atresia
Absent anus
Anal stenosis
Narrowing of anal opening
Absence of eyeballs
Failure of development of eyeball
Missing eyeball
No eyeball

[ more ]

Bifid tongue
Cleft tongue
Forked tongue
Split tongue

[ more ]

Dental crowding
Crowded teeth
Dental overcrowding
Overcrowding of teeth

[ more ]

Dental malocclusion
Bad bite
Malalignment of upper and lower dental arches
Misalignment of upper and lower dental arches

[ more ]

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 ]

External ear malformation
Female pseudohermaphroditism
Wide-set eyes
Widely spaced eyes

[ more ]

Hypoplasia of penis
Underdeveloped penis
Laryngeal stenosis
Low-set, posteriorly rotated ears
Abnormally small eyeball
Scrotal hypoplasia
Smaller than typical growth of scrotum
Toe syndactyly
Fused toes
Webbed toes

[ more ]

Vaginal atresia
Abnormally closed or absent vagina
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 ]

Wide pubic symphysis
5%-29% of people have these symptoms
Abnormal hair pattern
Abnormal distribution of hair
Abnormal lung lobation
Abnormality of cardiovascular system morphology
Atresia of the external auditory canal
Absent ear canal
Bicornuate uterus
Heart shaped uterus
Heart-shaped uterus

[ more ]

Calvarial skull defect
Cranial defect
Skull defect

[ more ]

Cleft ala nasi
Cleft nostril
Cleft upper lip
Conductive hearing impairment
Conductive deafness
Conductive hearing loss

[ more ]

Undescended testes
Undescended testis

[ more ]

Death in infancy
Infantile death
Lethal in infancy

[ more ]

Ectopic anus
Abnormal anus position
High palate
Elevated palate
Increased palatal height

[ more ]

Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific

[ more ]

Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

Midline nasal groove
Central nasal groove
Pulmonary hypoplasia
Small lung
Underdeveloped lung

[ more ]

Subglottic stenosis
Tracheal stenosis
Narrowing of windpipe
Umbilical hernia
Underdeveloped nasal alae
Underdeveloped tissue around nostril
Urethral atresia


Fraser syndrome is a genetic (inherited) disorder. It is caused by mutations in three different genesFRAS1, 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]


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.

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.

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 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.


  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; https://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; https://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. https://ageing.oxfordjournals.org/content/35/6/642.full.

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