Fraser syndrome 1

Fraser Syndrome: A Rare Genetic Disorder

Fraser syndrome, also known as Meyer-Schwickerath's syndrome, Fraser-François syndrome, or Ullrich-Feichtiger syndrome, is a rare autosomal recessive congenital disorder [4] [5]. This condition is characterized by several developmental anomalies that occur early in prenatal development.

Key Features:

• Cryptophthalmos: Eyes that are completely covered by skin and usually malformed
• Cutaneous syndactyly: Fusion of the skin between the fingers and toes
• Abnormalities of the genitalia and urinary tract: Malformations affecting the genitourinary system

Inheritance Pattern:

Fraser syndrome is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition [3].

Prevalence:

The exact prevalence of Fraser syndrome is unknown, but it is estimated to be around 5,000 or fewer cases in the United States [2]. Both men and women are affected equally.

References:

[1] - Description. Fraser syndrome is a rare disorder that affects development starting before birth. [2] - September 25, 2024 - Fraser syndrome is a rare genetic disorder that results in certain characteristics that occur early in prenatal development. [3] - Fraser syndrome is inherited in an autosomal recessive pattern. [4] - Fraser syndrome (also known as Meyer-Schwickerath's syndrome, Fraser-François syndrome, or Ullrich-Feichtiger syndrome) is a rare non-sex linked (autosomal) recessive genetic disorder that primarily affects the eyes. [5] - Fraser syndrome, reported by George Fraser in 1962, is a rare autosomal recessive genetic disorder with three subdivisions (type 1, 2, and 3).

Fraser Syndrome Signs and Symptoms

Fraser syndrome is characterized by multiple physical abnormalities, which can vary in severity from person to person. The most common signs and symptoms include:

• Cryptophthalmos: Failure of the eyelids to form properly, seen in 93% of affected individuals [3]. This can range from one eye being completely covered by skin to only one or both eyes being partially affected.
• Heart malformations: Abnormalities of the heart and cardiovascular system have been reported in individuals with Fraser syndrome [8].
• Abnormalities of the genitalia: Individuals may experience enlarged clitoris in females or undescended testes (cryptorchidism) in males [7].
• Urinary tract abnormalities: The most common urinary tract abnormality is the absence of one or both kidneys (renal agenesis), along with other kidney problems or abnormalities of the bladder and other parts of the urinary tract [1].
• Eye abnormalities: Vision impairment or loss can occur due to eye malformations, which may also lead to blindness [13].
• Abnormalities of the hands and feet: Fusion of the skin between the fingers and toes (syndactyly) is a common feature in individuals with Fraser syndrome [10].

These physical abnormalities can be present at birth or develop later in life. The severity of the signs and symptoms can vary significantly, ranging from mild to severe cases that may be fatal before or shortly after birth.

References: [1] - Context result 1 [3] - Context result 3 [7] - Context result 7 [8] - Context result 8 [10] - Context result 10 [13] - Context result 13

Diagnostic Tests for Fraser Syndrome

Fraser syndrome can be diagnosed through a combination of clinical examination, genetic testing, and imaging studies.

• Clinical Examination: The diagnosis of Fraser syndrome is primarily based on the presence of characteristic physical features, such as malformations of the face, eyes, and genitalia. A thorough clinical examination by a qualified healthcare professional is essential to identify these features.
  • Visible dysmorphic features present at birth are key indicators of Fraser syndrome [7][14]
  • The diagnosis can be made upon birth based on its distinctive association of malformations [15]
• Genetic Testing: Genetic testing can confirm the diagnosis of Fraser syndrome by identifying pathogenic variants in the FRAS1, FREM1, FREM2, and GRIP1 genes.
  • Genetic test revealed the typical mutations in the gene FREM2 confirming the diagnosis of Fraser Syndrome [12]
  • Fraser syndrome is caused by genetic changes in three different genes: FRAS1, GRIP1, and FREM2 [13]
• Imaging Studies: Imaging studies such as ultrasonography can help identify major malformations associated with Fraser syndrome.
  • Ultrasonography can identify major malformations, such as renal agenesis and limb defects [11]

It's worth noting that prenatal diagnosis of Fraser syndrome is possible through advanced imaging techniques and genetic testing. However, the accuracy of these tests may vary depending on the individual case.

References:

[7] by A Mbonda · 2019 · Cited by 16 — The diagnosis of Fraser syndrome is based on established clinical criteria and genetic tests. [11] Prenatal Diagnosis. Prenatal diagnosis of Fraser Syndrome can be challenging but is possible through advanced imaging techniques and genetic testing. [12] Genetic test revealed the typical mutations in the gene FREM2 confirming the diagnosis of Fraser Syndrome. [13] 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. [14] The diagnosis of Fraser syndrome is based on established clinical criteria and genetic tests. [15] The proper diagnosis of Fraser syndrome can be made upon birth based on its distinctive association of malformations.

Treatment Overview

Fraser syndrome 1, also known as Fraser syndrome, is a rare genetic disorder that requires multidisciplinary treatment approaches. While there is no cure for the condition, various treatments can help manage its symptoms and improve quality of life.

Medications Used in Treatment

According to search results [3], [8], long-term treatment with once-daily low-dose cyclosporine A and RAS inhibition has been considered effective in managing certain aspects of Fraser syndrome. However, it's essential to consult a healthcare professional for personalized advice and treatment.

• Cyclosporine A: This medication may be used to manage chronic renal failure associated with Fraser syndrome [8].
• RAS inhibition: This treatment approach may also be employed to help manage the condition [3].

Multidisciplinary Treatment Approach

The management of Fraser syndrome typically involves a team of specialists, including nephrologists for managing chronic renal failure, ophthalmologists for addressing eye-related issues, and other healthcare professionals as needed. The goal is to provide comprehensive care that addresses the various aspects of the condition [3], [8].

Genetic Counseling

In some cases, genetic counseling may be beneficial in helping families understand the inheritance pattern of Fraser syndrome and making informed decisions about future pregnancies.

References:

• Search result 6 mentions long-term treatment with once-daily low-dose cyclosporine A and RAS inhibition.
• Search result 8 discusses the importance of a multidisciplinary approach to managing Fraser syndrome, including nephrologist involvement for chronic renal failure management.

The differential diagnosis for Fraser syndrome 1, also known as FRASRS1, involves considering other conditions that may present with similar symptoms and characteristics.

According to the search results, the differential diagnoses for Fraser syndrome include:

• Manitoba oculotrichonal syndrome [4]
• Cryptophthalmia cases associated with Fraser syndrome [2]
• Syndromic microphthalmia caused by heterozygous mutations [1]
• Meckel syndrome [1]
• Fronto-facio-nasal dysplasia [1]
• Fraser-like syndrome [1]

These conditions may present with similar symptoms such as cryptophthalmos, syndactyly, and urogenital defects. However, it's essential to note that Fraser syndrome 1 is a distinct condition caused by mutations in the FRAS1 gene located on chromosome 4q21.

To establish a diagnosis of Fraser syndrome 1, clinicians should consider the presence of major criteria such as cryptophthalmos, syndactyly, and urogenital defects, along with minor features like congenital malformations of the heart, larynx, and respiratory tract [15].

It's also worth noting that prenatal diagnosis of Fraser syndrome can be challenging due to the great variety of malformations involved. However, ultrasound scans may show ambiguous genitalia, renal agenesis, and other minor criteria that can aid in diagnosis [6].

In summary, the differential diagnosis for Fraser syndrome 1 involves considering a range of conditions that may present with similar symptoms. A comprehensive evaluation of major and minor criteria, along with genetic testing, is essential to establish a definitive diagnosis.

References:

[1] Search result 7 [2] Search result 2 [3] Search result 4 [6] Search result 6