Fraser syndrome 2

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 genetic disorder characterized by several developmental anomalies. The condition was first described by Canadian geneticist George R. Fraser in 1962.

Key Features of Fraser Syndrome

• Cryptophthalmos: A rare congenital malformation where the eyelids are completely covered by skin and usually malformed.
• Syndactyly: Fusion of the skin between the fingers and toes.
• Abnormalities of the genitalia and urinary tract: The condition often affects the genitourinary system, leading to various anomalies.

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. There is currently no cure for FS, but surgery may be available to correct some malformations associated with this disorder.

Prevalence

The exact prevalence of Fraser syndrome is unknown, but it is estimated to affect fewer than 5,000 individuals in the United States.

References:

• [1] Description. Fraser syndrome is a rare disorder that affects development starting before birth.
• [2] Fraser syndrome is an autosomal recessive congenital disorder, identified by several developmental anomalies.
• [3] There is currently no cure for FS but surgery is available to correct some malformations associated with this disorder, depending on the severity of the malformations.
• [4] Fraser syndrome is a rare genetic disorder that results in certain characteristics that occur early in prenatal development.
• [5] Fraser syndrome (also known as Meyer-Schwickerath's syndrome, Fraser-François syndrome, or Ullrich-Feichtiger syndrome) is an autosomal recessive congenital disorder, identified by several developmental anomalies.

Fraser syndrome is a rare genetic disorder characterized by several malformations that are present at birth [2]. Some of the common signs and symptoms of Fraser syndrome include:

• Eye abnormalities: Individuals with Fraser syndrome can have eye problems such as cryptophthalmos (where one or both eyes are partially or completely covered in skin), microphthalmia (small eyes), or anophthalmia (absence of one or both eyes) [3, 4].
• Fused eyelids: Cryptophthalmos is a characteristic feature of Fraser syndrome, where the eyelid and eye socket are fused together [4].
• Syndactyly: This refers to the fusion of skin between the fingers and toes [4].
• Genital abnormalities: Individuals with Fraser syndrome can have abnormalities of the genitalia, such as an enlarged clitoris in females or undescended testes (cryptorchidism) in males [6].
• Urinary tract abnormalities: Renal agenesis (absence of one or both kidneys), urinary tract obstruction, and other kidney problems are common in individuals with Fraser syndrome [5].
• Heart malformations: Heart defects can also occur in individuals with Fraser syndrome [7].
• Respiratory tract abnormalities: Abnormalities of the larynx (voice box) and trachea can lead to breathing difficulties [8].

It's worth noting that each individual with Fraser syndrome may have a unique combination of these signs and symptoms, and not everyone will experience all of them.

Diagnostic Tests for Fraser Syndrome 2

Fraser syndrome 2 (FRASRS2) can be diagnosed through various tests, including genetic testing and clinical evaluation.

• Genetic Testing: Genetic testing for mutations in the FRAS1-related extracellular matrix protein 2 (FREM2) gene can confirm the diagnosis of Fraser syndrome 2. This test is particularly useful when a familial mutation is known, allowing for amniocentesis or chorionic villus sampling to be utilized for genetic analysis [10].
• Clinical Evaluation: A clinical evaluation by a healthcare professional is essential in diagnosing Fraser syndrome 2. The presence of characteristic features such as cryptophthalmos, syndactyly, and abnormalities of the respiratory and urogenital tract can aid in diagnosis [2]. Additionally, ultrasound imaging can identify major malformations, such as renal agenesis and limb defects [10].
• DNA Testing: DNA testing is useful to distinguish Fraser syndrome 2 from other conditions with similar symptoms. This test can confirm the presence of genetic mutations associated with Fraser syndrome 2 [13].

Diagnostic Criteria

The diagnosis of Fraser syndrome 2 is confirmed in the presence of either three major, or two major and two minor, or one major and three minor diagnostic criteria [14]. These criteria include:

• Major Diagnostic Criteria: Cryptophthalmos, syndactyly, and abnormalities of the respiratory and urogenital tract.
• Minor Diagnostic Criteria: Abnormal genitalia or dysplastic ears.

Differential Diagnosis

Fraser syndrome 2 can be differentiated from other conditions with similar symptoms through a comprehensive clinical evaluation. The differential diagnoses include ablepharon-macrostomia, fronto-facio-nasal dysplasia, Fraser-like syndrome, Meckel syndrome, and syndromic microphthalmia caused by heterozygous mutations [14].

References

[2] van Haelst et al., 2008 [10] Mbonda et al., 2019 [13] De Bernardo et al., 2015 [14] Kornacki et al., 2020

Based on the provided context, it appears that there are limited treatment options available for Fraser syndrome 2 (FRASRS2). However, I was able to find some relevant information in the search results.

According to search result [12], Nobias Therapeutics has announced that the FDA has granted rare pediatric disease designation and orphan drug designation to their small-molecule metabotropic glutamate receptor modulator NB-001 for the treatment of Fraser syndrome. This suggests that there may be potential therapeutic options being explored, although it's essential to note that this information is from 2024.

Unfortunately, I couldn't find any specific information on the effectiveness or availability of drug treatments for FRASRS2 in the provided context. However, search result [15] mentions that treatment options for Fraser syndrome are currently limited despite progress made in terms of genetics.

It's also worth noting that search results [9] and [11] mention that there is no specific treatment for Fraser syndrome, and reconstructive and cosmetic surgery has been attempted with the goal of optimizing visual potential. However, these statements seem to be more general and not specifically related to FRASRS2.

In summary, while there may be some potential therapeutic options being explored for Fraser syndrome 2, it appears that there is limited information available on specific drug treatments for this condition. Further research or consultation with a healthcare professional would be necessary to determine the most effective course of treatment.

References: [12] Nobias Therapeutics announces FDA grants rare pediatric disease designation and orphan drug designation to NB-001 for Fraser syndrome. [15] Mbonda, A. (2019). Treatment options for Fraser syndrome are currently limited despite progress made in terms of genetics.

Based on the context provided, it appears that Fraser syndrome 2 (FRASRS2) is caused by mutations in the FRAS1-related extracellular matrix protein 2 (FREM2) gene.

When considering a differential diagnosis for Fraser syndrome 2, some potential conditions to consider are:

• Fraser syndrome 3: This is another form of Fraser syndrome that is also associated with genetic mutations.
• Cryptophthalmos-syndactyly syndrome: This condition is characterized by cryptophthalmos (a rare congenital anomaly where the eyelids do not fully separate) and syndactyly (webbed fingers or toes).
• Opitz syndrome: Also known as G syndrome, this is a rare genetic disorder that can cause various physical abnormalities, including cryptophthalmos.
• Smith-Lemli-Opitz syndrome: This is a metabolic disorder that can cause a range of congenital anomalies, including cryptophthalmos and syndactyly.

It's worth noting that Fraser syndrome 2 is a relatively rare condition, and the differential diagnosis may vary depending on the specific clinical presentation and genetic findings. A thorough evaluation by a medical professional with expertise in genetics or pediatric medicine would be necessary to determine the most likely diagnosis.

References:

• Context point 1: Oct 30, 2020 — Fraser syndrome 2 (FRASRS2) is caused by mutations in the FRAS1-related extracellular matrix protein 2 (FREM2) gene.
• Context point 7: Fraser syndrome is a rare, autosomal recessive disorder characterized by cryptophthalmos, syndactyly, and renal agenesis or obstructive uropathy.