Fraser syndrome

Fraser syndrome is a rare genetic disorder that results in certain characteristics that occur early in prenatal development [3]. The condition is characterized by several malformations that are present at birth, including:

• Cryptophthalmos: eyes that are completely covered by skin and usually malformed
• Syndactyly: fusion of the skin between fingers or toes
• Urogenital anomalies: abnormalities in the urinary and reproductive systems

Fraser syndrome is an autosomal recessive congenital disorder, identified by several developmental anomalies [6]. The condition is named for the geneticist who first described it.

The incidence of Fraser syndrome is very low, with approximately 0.04 cases per 10,000 live births [7]. The condition can affect various parts of the body, including the head, lungs, kidneys, and limbs.

Fraser syndrome is a rare congenital malformation syndrome characterized by cryptophthalmos, syndactyly, and urogenital defects [9]. The diagnosis may be challenging due to the complexity of the symptoms.

Overall, Fraser syndrome is a rare and complex genetic disorder that requires careful diagnosis and management.

Fraser Syndrome Signs and Symptoms

Fraser syndrome, also known as cryptophthalmos-syndactyly syndrome, is a rare genetic disorder that affects various parts of the body. The condition can manifest in different ways, but some common signs and symptoms include:

• Eye abnormalities: One or both eyes may be completely covered by skin (cryptophthalmos), partially covered, or small in size.
• Heart malformations: Abnormalities of the heart can occur, which may lead to vision impairment or loss.
• Voicebox (larynx) abnormalities: The voicebox may be affected, leading to respiratory problems.
• Liver malformations: Intrahepatic biliary atresia, a condition where the bile ducts are absent or blocked, can occur.
• Small eyes (microphthalmia): One or both eyes may be smaller than normal.
• Fusion of skin between the eyes and nose: The skin between the eyes and nose may be fused together.
• Other developmental anomalies: Individuals with Fraser syndrome may also experience abnormalities in the hands, feet, genitalia, and urinary tract.

Severity and Impact

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 longer, but they may still experience significant health issues and developmental delays.

References

• [1] Fraser syndrome is an autosomal recessive congenital disorder, identified by several developmental anomalies. (Source: #7)
• Eye abnormalities can lead to vision impairment or loss, and individuals may also have abnormalities of the hands, feet, genitalia, and urinary tract. Other signs and symptoms include heart malformations, voicebox abnormalities, liver malformations, small eyes, fusion of skin between the eyes and nose, and other developmental anomalies. (Source: #8)
• Ultrasound findings of the head may include cryptophthalmos, microcephaly, hydrocephalus, neural tube defects, facial cleft, hypertelorism, nose and ear abnormalities. (Source: #9)

Diagnostic Tests for Fraser Syndrome

Fraser syndrome can be diagnosed through a combination of clinical evaluation and genetic testing.

• Clinical Evaluation: The diagnosis of Fraser syndrome is based on established clinical criteria, which include visible dysmorphic features present at birth [14]. These features may include malformations such as renal agenesis, limb defects, and eye abnormalities. In some cases, prenatal ultrasonographic features such as polyhydramnios or oligohydramnios, echogenic lungs, and renal abnormalities or agenesis can also be indicative of the syndrome [15].
• Genetic Testing: Genetic testing can confirm a Fraser syndrome diagnosis by identifying pathogenic variants in the FRAS1, FREM1, FREM2, and GRIP1 genes [5]. This type of testing is particularly useful when there is a family history of the condition or when the clinical features are ambiguous.

Diagnostic Teams

A diagnostic team for Fraser syndrome may include:

• Gastroenterology: To evaluate gastrointestinal symptoms
• Genetics: To confirm the diagnosis through genetic testing
• Nephrology: To assess renal function and abnormalities
• Neurology: To evaluate neurological symptoms and developmental delays

Prenatal Diagnosis

Prenatal diagnosis of Fraser syndrome can be challenging but is possible through advanced imaging techniques and genetic testing. Ultrasonography can identify major malformations, such as renal agenesis and limb defects [11]. If a familial mutation is known, amniocentesis or chorionic villus sampling can be utilized for genetic testing.

References

[5] Mbonda, A. (2019). The diagnosis of Fraser syndrome is based on established clinical criteria and genetic tests. The criteria enabling clinical diagnosis are visible dysmorphic features present at birth, hence, Fraser syndrome can easily diagnosed at birth, except when health professionals are inexperienced in clinical recognition.

[9] Boyd et al. (1988) suggested that prenatal diagnosis by ultrasound examination of eyes, digits, and kidneys should detect the severe form of the syndrome.

[11] Prenatal Diagnosis. Prenatal diagnosis of Fraser Syndrome can be challenging but is possible through advanced imaging techniques and genetic testing. Ultrasonography can identify major malformations, such as renal agenesis and limb defects. If a familial mutation is known, amniocentesis or chorionic villus sampling can be utilized for genetic ...

[14] The diagnosis of Fraser syndrome is based on established clinical criteria and genetic tests. The criteria enabling clinical diagnosis are visible dysmorphic features present at birth, hence, Fraser syndrome can easily diagnosed at birth, except when health professionals are inexperienced in clinical recognition.

[15] Less severely affected individuals can live into childhood or adulthood. Fraser syndrome is caused by genetic changes in three different genes: FRAS1, GRIP1, and FREM2 and is inherited in an autosomal recessive manner. This condition is diagnosed based on signs and symptoms. Genetic testing may be useful to confirm the diagnosis.

Treatment Overview

Fraser syndrome, a rare genetic disorder, requires multidisciplinary treatment approaches to manage its various symptoms and complications. While there is no cure for the condition, drug treatments can help alleviate some of the associated issues.

• Nephrotic Syndrome Management: In cases where Fraser syndrome leads to nephrotic syndrome, medical therapy may be initiated to protect the kidneys and prevent further damage [6].
• Gonadal Tumors Treatment: Some individuals with Fraser syndrome may develop gonadal tumors. Treatment for these tumors typically involves surgical removal [6].
• Symptomatic Relief: Medications can help manage symptoms such as pain, bleeding, or endometriosis-related issues [15].

Multidisciplinary Approach

Effective treatment of Fraser syndrome often requires a team of healthcare professionals, including:

1. Nephrologists for managing chronic renal failure and nephrotic syndrome
2. Surgeons for surgical interventions, such as tumor removal
3. Ophthalmologists for addressing eye-related issues
4. ENT specialists for treating ear, nose, and throat anomalies
5. Other specialists as needed to address specific complications

Important Considerations

While drug treatments can provide relief from some symptoms, it's essential to note that Fraser syndrome is a complex condition requiring comprehensive care. Consultation with a healthcare professional is crucial for developing an individualized treatment plan.

References:

[6] Shao Q (2023) - Current management of Fraser syndrome [cited by 3]

[15] March 16, 2020 - Case report on endometriosis in Fraser syndrome

Fraser syndrome is a rare congenital malformation syndrome characterized by cryptophthalmos, syndactyly, and urogenital defects [6]. When diagnosing Fraser syndrome, it's essential to consider differential diagnoses that may present similar symptoms. Here are some conditions that should be considered in the differential diagnosis of Fraser syndrome:

• Renal agenesis: This condition is characterized by the absence or underdevelopment of one or both kidneys. It has been associated with Fraser syndrome, and a diagnosis of renal agenesis should prompt further investigation for Fraser syndrome [9].
• Cryptophthalmos spectrum: This condition refers to a range of abnormalities in the development of the eyelids and eyes, which can be seen in Fraser syndrome. A diagnosis of cryptophthalmos spectrum should raise suspicion for Fraser syndrome [8].
• Syndactyly: This condition is characterized by the fusion of two or more fingers or toes. It is a common feature of Fraser syndrome, but it can also occur as an isolated condition.
• Urogenital defects: These defects can include abnormalities in the development of the kidneys, ureters, bladder, and genitalia. They are a key feature of Fraser syndrome, but they can also occur as part of other conditions.

It's essential to note that a diagnosis of Fraser syndrome is typically made based on a combination of clinical features, including cryptophthalmos, syndactyly, urogenital defects, and other abnormalities [7]. A thorough examination and diagnostic workup are necessary to confirm the diagnosis and rule out other potential causes of these symptoms.

References:

[6] Fraser syndrome is a rare congenital malformation syndrome characterized by cryptophthalmos, syndactyly, and urogenital defects. [8] FS is characterized by unilateral or bilateral cryptophthalmos (skin covering the eyes), with or without underlying abnormalities of the eye; [7] include six major manifestations (syndactyly, cryptophthalmos spectrum, ambiguous genitalia, urinary tract abnormalities, laryngeal and tracheal ... [9] fraser syndrome is an important differential diagnosis in fetuses with renal agenesis and has a high perinatal mortality due to the consequences of ...