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Fraser Syndrome

Fraser syndrome is a rare, autosomal recessive disorder characterized by cryptophthalmos and syndactyly.


Multiple physical abnormalities are the major signs of Fraser Syndrome. Some of the most common ones are middle and outer ear deformities, partial fusion of the fingers and toes (syndactyly), complete fusion of the eyelids (cryptophthalmos) and malformed or missing kidneys (renal agenesis) as already discussed above [5].

However, patients often present a broad nose with deep indentations and a flattened bridge on both sides of the nostril.

In some patients, there may be hair growth extending from the forehead down to the eyebrows, cleft or high palate, malformation of the eyelid ducts (responsible for the conveyance of tears), widely spaced nipples, displaced navel, missing or malformed larynx, malformation of the pubic bones and in rare cases, mental deficiency.

Incomplete genital development is another strong indication of this syndrome. In male patients, failure of the testicles to descend into the scrotum and abnormal urethral opening often to the underside of the penis is common [6]. In females, an enlarged clitoris (clitoromegaly), malformed fallopian tubes, fused vaginal opening and birconate uterus are commonly presented.

There are some conditions closely related to the Fraser syndrome and so the symptoms of those diseases can show similarities to those reported for the Fraser syndrome. For a differential diagnosis, proper comparisons will be useful [7].

Bilateral renal agenisis: This is the absence of both kidneys at birth. It is a genetic disorder that is characterized by the inability of the kidneys to develop properly in a fetus. With the absence of kidneys comes a deficiency of amniotic fluid in pregnant women. The amniotic fluid is responsible for providing cushion for the developing fetus. When this fluid is insufficient, the fetus will be compressed leading to more malformations for the baby at birth.

Coloboma of iris-anal atreiss syndrome: Also known as the cat-eye syndrome, this ailment is characterized by a fissure in the iris of the eye and the lack of an anal opening (renal agenesis) may also be present.

Branchio-oto-renal syndrome: Also known as the Melnick-Fraser syndrome, this is a genetic disorder that is characterized by kidney malformations, hearing loss and renal agenesis.

Multiple Congenital Anomalies
  • She had multiple congenital anomalies which included a cardiac defect and airway abnormalities. Intubation difficulties were circumvented by the retrograde technique of placement of the tracheal tube.[ncbi.nlm.nih.gov]
  • Cryptophthalmos refers to a group of uncommon congenital anomalies of eyelid formation that can occur alone or in combination with multiple congenital anomalies as part of the Fraser syndrome.[ncbi.nlm.nih.gov]
  • Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes. National Library of Medicine. nd. 2pp. www.nlm.nih.gov/mesh/jablonki/syndromes/syndrome302.html[rarediseases.org]
  • Parents and healthy siblings of patients will also be included for genetic study, and parents of children with undiagnosed multiple congenital anomalies syndromes will be included for comparison study.[clinicaltrials.gov]
  • We report a case of 13-year-old male, who had multiple congenital anomalies and clinico radiological features consistent with Fraser syndrome without cryptophthalmos.[jclpca.org]
  • The dental anomalies consist of delayed dental development, congenital absence of the second premolars, microdontia of the deciduous molars. A fibrous band of the buccal mucosa was found.[ncbi.nlm.nih.gov]
Severe Brachydactyly
  • We note severe brachydactyly is a manifestation of Fraser syndrome and found a novel homozygous splice site variation c.3293-2A T in FRAS1.[ncbi.nlm.nih.gov]
Ear Deformity
  • Some of the most common ones are middle and outer ear deformities, partial fusion of the fingers and toes (syndactyly), complete fusion of the eyelids (cryptophthalmos) and malformed or missing kidneys (renal agenesis) as already discussed above.[symptoma.com]
  • Lop-ear deformity. 3. Preauricular pits. 4. Preauricular tags. 5. External auditory canal: stenosis 6. Middle ear: ossicular malformations, such as hypoplasia or displacement 7.[medicine.uiowa.edu]
Dysplastic Ears
  • Minor criteria included anorectal defects, dysplastic ears, skull ossification defects, umbilical abnormalities, and nasal anomalies.[en.wikipedia.org]
Widely Spaced Nipples
  • The patient had microphthalmia, blindness, widely spaced nipples, bifid ureter, syndactyly of the toes, and mental retardation. Sonography showed the presence of a uterus and intra-abdominal gonads.[ncbi.nlm.nih.gov]
  • 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[rarediseases.info.nih.gov]
  • Some of the other defects associated with Fraser Syndrome are hair growth extending from forehead to eyebrows, malformation of eyelid ducts, widely spaced nipples, along with mental impairment.[epainassist.com]
  • In some patients, there may be hair growth extending from the forehead down to the eyebrows, cleft or high palate, malformation of the eyelid ducts (responsible for the conveyance of tears), widely spaced nipples, displaced navel, missing or malformed[symptoma.com]
  • The baby had malformed and low-set ears, wide nasal bridge, pseudo-hypertelorism, widely spaced nipples and fused labia with adhesion. The oral cavity, limbs, digits, spine and vertebrae and other systems were normal.[ojoonline.org]


Diagnosing the Fraser syndrome begins with a comprehensive look at the family history and physical examination. The confirmation is straightforward and imaging devices can be used in difficult situations [8].

  • We describe a neonate with this syndrome having colonic atresia leading to cecal rupture and pneumoperitoneum.[ncbi.nlm.nih.gov]
  • We describe a neonate with this syndrome having colonic atresia leading to cecal rupture and pneumoperitoneum. Key words Colonic atresia Cryptophthalmos Fraser syndrome This is a preview of subscription content, log in to check access. References 1.[doi.org]
Delayed Bone Age
  • We report on an 8-year-old Thai girl with bilateral complete cryptophthalmos, facial asymmetry, delayed bone age, brachymesophalangy and medial deviation of the second toes, and dental anomalies.[ncbi.nlm.nih.gov]
  • The proband was screened for mtDNA mutations because of chronic gastrointestinal pseudo-obstruction, urinary tract dysmotility, seizures, mental retardation and persistent macrocytosis, as well as the intermittent elevation of methylmalonic acid.[ncbi.nlm.nih.gov]


Treatment is based on provision of close and regular support.


The condition is often fatal if renal agenesis is present. Also, surgical repair when cryptophthalmous is the main symptom is far from 100% effective as only poor vision will be recorded [9].


Fraser syndrome is an autosomal recessive genetic defect. The mutant gene that causes the condition has been traced to the 4q21 (long arm of the chromosome 4). The genetic information for every individual is found in chromosomes located in the nucleus of the human cells. The cells in the human body come with 46 chromosomes. The human chromosomes are numbered from 1-22 with the sex chromosomes denoted as X and Y [3].

Females have two X chromosomes but males have one X and one Y chromosomes. All the chromosome come with a short arm labeled as “p” and the long arm labeled as “p”. The arms are further categorized into many numbered bands. Therefore for instance, the “chromosome 4q21” refers to band 21 located on the long arm of the 4th chromosome. The numbered bands show where the thousands of genes present on each chromosome are located.

Genetic diseases such as the Fraser syndrome are determined by the combination of genes for a particular trait which are on the chromosomes received from each parent.

When an individual inherits the same abnormal gene for the same trait from each parent, recessive genetic ailments occur. The individual becomes an asytompatic carrier of the disease condition when he or she receives one gene for the disease and one normal gene.

For parents who are carriers, the chance of passing on the defective gene to produce an affected child is 25% for each pregnancy. There is a 50% chance that the child will be a carrier of the condition like the parent. There is also a 25% chance that the child will receive normal genes from both parents and stay normal for the particular trait.

All individuals in the family will have some of the abnormal genes. For parents who are consanguineous, there is a higher chance of carry the same abnormal gene in comparison to parents that are unrelated. This means that consanguineous parents have a higher chance of producing children with a recessive genetic defect.


The Fraser syndrome affects both females and males in equal proportions. The syndrome has been classified as rare because the incidence is 0.043 per 10,000 for live born infants and 1.1 in 10,000 for all still birth cases [2].

Sex distribution
Age distribution


Fraser syndrome in infants comes with renal malformations that may include dysplasia (improper development), hypoplasia (underdevelopment) and unilateral or bilateral renal agenesis (absence of one or both kidneys). The may also show additional abnormalities such as malformations of the middle ear and the outer ear. This may result in hearing impairment [4].

In affected males, there may be cryptorchidism (failure of one or two testes to descend), hypospadias (abnormal placement of the urinary opening), micropenis (abnormally small penis).

For females with the Fraser syndrome, clitoromegaly (abnormally enlarged clitoris), bicornate uterus (abnormaly shaped uterus and malformed fallopian tubes are common. Also, the labia (folds of skin on either side of the vagina) may be fused abnormally.


There are no guidelines for prevention of Fraser Syndrome.


Fraser syndrome is typically depicted by a partial webbing of the toes and fingers. It is a rare genetic defect.

Apart from partial syndactyly, the condition is equally characterized by cryptophthalmos (fusion of the eyelids), renal abnormalities and genital malformations [1]. When cryptophthlamos is present, blindness is almost certain.

Patient Information

The importance of genetic counseling for both parents and children with this disorder cannot be overemphasized. This is because giving birth to one child with this condition means that there is an increased possibility of having another.

If the parents have the recessive genes for the condition they can be counseled on the dangers of giving birth to a child with this defect. This will ensure that the parents are fully aware of what they face if their child is diagnosed with the disorder.

Treatment is based on provision of close and regular support and so a close relationship with the medical personnel is very important [10]. There is no total cure for the condition yet.

Parents of children with the Fraser Syndrome are advised to seek out support groups around them. This will alleviate the challenges faced to an extent. The local clinic should be able to provide information on such support groups.



  1. Okumus N, Onal EE, Turkyilmaz C, et al. Resuscitation failure in a newborn undiagnosed in the prenatal period. Reuscitation. 2005;65:221-23.
  2. Wong LJ, Lin YH Suwannarat P, et al. Mitochondrial DNA mutations in a patient with sex reversal and clinical features consistent with Fraser syndrome. Clin Genet. 005;67:252-57.
  3. Hambire SD, Bhavsar PP, Jayakar AV. Fraser-Cryptophthalmos syndrome with cardiovascular malformations: a rare association. Indian Pediatr. 2003;40:888-90.
  4. Vrontou S, Petrou P, Meyer BI, et al. Fras1 deficiency results in cryptophthalmos, renal agenesis and blebbed phenotype in mice. Nat Genet. 2003;34:209-14.
  5. McGregor L, Makela V, Darling SM, et al. Fraser syndrome and mouse blebbed phenotype caused by mutations in FRAS1/Fras1 encoding a putative extracellular matrix protein. Nat Genet. 2003;34:203-08.
  6. Martinez-Frias ML, Bermejo Sanchez E, Felix V, Calvo Celada R, Ayala Garces A, Hernandez Ramon F Fraser syndrome: frequency in our environment and clinical-epidemiological aspects of a consecutive series of cases. An Esp Pediatr 1998 Jun;48(6):634-8
  7. Ozgunen T, Evruke C, Kadayifci O, Demir C, Aridogan N, Vardar MA Fraser syndrome. Int J Gynaecol Obstet 1995 May;49(2):187-9
  8. Stevens CA, McClanahan C, Steck, A, Shiel FOM, Carey JC. Pulmonary hyperplasia in the Fraser cryptophthalmos syndrome. Am. J. Med. Genet. 52: 427-431, 1994.
  9. Lesniewicz R, Midro AT: Ultrasound diagnosis of four fetuses with Fraser syndrome during pregnancy. Ginekol Pol 1998 Mar;69(3):152-7
  10. Fryns JP, van Schoubroeck D, Vandenberghe K, Nagels H, Klerckx P Diagnostic echographic findings in cryptophthalmos syndrome (Fraser syndrome). Prenat Diagn 1997 Jun;17(6):582-4

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Last updated: 2019-07-11 21:50