cardiofaciocutaneous syndrome 2

Cardiofaciocutaneous Syndrome 2 (CFC2) Description

Cardiofaciocutaneous syndrome 2, also known as KRAS-related cardiofaciocutaneous syndrome, is a rare genetic disorder that affects multiple parts of the body. The condition is characterized by cardiac abnormalities, including:

• Pulmonic stenosis and other valve dysplasias
• Septal defects
• Hypertrophic cardiomyopathy
• Rhythm disturbances

In addition to heart problems, CFC2 syndrome also involves facial features and skin issues, such as:

• Dysmorphic craniofacial features
• Skin and hair abnormalities
• Hypotonia (low muscle tone)
• Eye abnormalities
• Gastrointestinal dysfunction
• Seizures
• Varying degrees of neurocognitive delay

This condition is a form of cardiofaciocutaneous syndrome, which is a multiple congenital anomaly disorder. The exact cause of CFC2 syndrome is not well understood, but it is believed to be related to mutations in the KRAS gene.

References:

• [14] Cardiofaciocutaneous syndrome 2 Synonyms KRAS-Related Cardiofaciocutaneous Syndrome. Summary Excerpted from the GeneReview: Cardiofaciocutaneous Syndrome.
• [10] Clinical Description of CFC syndrome, which includes similar features to CFC2 syndrome.

Early Signs and Symptoms

Cardiofaciocutaneous (CFC) syndrome can be difficult to diagnose, especially in its early stages. However, there are some signs and symptoms that may indicate the presence of this condition.

• Prenatal ultrasound: CFC syndrome can sometimes be discovered before birth, during prenatal ultrasound. Early signs include extra amniotic fluid (liquid surrounding the fetus) or a head and body that are larger than expected.
• Extra amniotic fluid: Extra amniotic fluid may make the womb feel larger than usual, which can lead to complications during pregnancy.

Common Signs and Symptoms

The signs and symptoms of CFC syndrome overlap significantly with those of two other genetic conditions, Costello syndrome and Noonan syndrome. However, there are some distinct features that can help diagnose this condition.

• Sparse, brittle, curly hair: One of the most distinctive features of CFC syndrome is unusually sparse, brittle, curly hair.
• Large head (macrocephaly): People with CFC syndrome often have a relatively large head or true macrocephaly.
• Heart defects: Cardiofaciocutaneous syndrome is characterized by cardiac abnormalities, including pulmonic stenosis and other valve dysplasias, septal defects, hypertrophic cardiomyopathy, rhythm disturbances.
• Skin abnormalities: Skin abnormalities occur in almost everyone with CFC syndrome. Many affected people have dry, rough skin; dark-colored moles (nevi); wrinkled skin; xerosis, hyperkeratosis, ichthyosis, keratosis pilaris, ulerythema ophryogenes, eczema, pigmented moles, hemangiomas.
• Feeding difficulties: Feeding difficulties, leading to failure to thrive, gastroesophageal reflux (GER), vomiting and constipation often appear in infancy but improve in childhood.

Other Symptoms

In addition to these common signs and symptoms, people with CFC syndrome may also experience other complications, such as:

• Hypertelorism: Wide spaced eyes
• Short stature
• Relative macrocephaly: A relatively large head
• Cognitive delay: Some people with CFC syndrome may experience cognitive delay or intellectual disability.

It's essential to note that every individual with CFC syndrome is unique, and not everyone will exhibit all of these signs and symptoms. If you suspect that you or a loved one has this condition, it's crucial to consult with a healthcare professional for proper diagnosis and treatment.

Diagnostic Tests for Cardiofaciocutaneous Syndrome 2

Cardiofaciocutaneous syndrome 2 (CFC2) is a rare genetic disorder that affects multiple parts of the body, including the heart, face, skin, and hair. Accurate diagnosis of CFC2 requires a combination of clinical evaluation and molecular genetic testing.

Molecular Genetic Testing

Molecular genetic testing is the preferred initial test for diagnosing CFC2. This type of testing can detect mutations in the KRAS gene, which is associated with CFC2 (1). Multigene panel testing, which examines multiple genes simultaneously, is also a recommended approach and can identify mutations in ∼70% to 90% of individuals with the clinical diagnosis of CFC (4).

Whole Exome Sequencing

Whole exome sequencing (WES) is another sophisticated genetic test that has been instrumental in diagnosing CFC2. This test examines the entirety of an individual's protein-coding genes and can identify mutations in multiple genes, including KRAS (9).

Serial Single-Gene Testing

If molecular genetic testing is unavailable, serial single-gene testing or sequential gene testing may be considered. This approach involves testing one gene at a time to identify the specific mutation associated with CFC2 (6).

Genetic Testing for Associated Conditions

In addition to diagnosing CFC2, genetic testing can also help identify associated conditions, such as Noonan syndrome and Costello syndrome.

References:

• [1] Cardiofaciocutaneous (CFC) syndrome is characterized by cardiac abnormalities, distinctive craniofacial appearance, and cutaneous abnormalities. Genetic testing can identify the gene mutation for accurate diagnosis.
• [4] Multigene panel testing is usually the preferred initial test and will detect a mutation in ∼70% to 90% of individuals with the clinical diagnosis of CFC.
• [6] Serial single-gene testing, the use of a multigene panel, and more complete genomic testing are all options for molecular testing.
• [9] The turning point in these diagnostic journeys came with whole exome sequencing. This sophisticated genetic test examines the entirety of an individual's protein-coding genes and can identify mutations in multiple genes, including KRAS.

Treatment Options for Cardiofaciocutaneous Syndrome

Cardiofaciocutaneous (CFC) syndrome, a rare genetic disorder, currently lacks specific treatment options. However, recent studies have explored the use of genetic pathway inhibitors, including MEK inhibitors, as potential therapeutic approaches.

• MEK Inhibitors: Research has shown that MEK inhibitors may be effective in decreasing seizures and have a low frequency of patients discontinuing treatment due to adverse effects [6]. This suggests that MEK inhibitors could be a viable option for managing certain symptoms associated with CFC syndrome.
• Other Medications: While there is no cure for CFC syndrome, medications may be used to manage specific symptoms such as seizures. Management strategies also involve addressing the various physical and developmental challenges associated with this condition [12].

Current Limitations

It's essential to note that:

• There is currently no standard treatment for CFC syndrome.
• Growth hormone is not a standard treatment for this condition

Differential Diagnoses for Cardiofaciocutaneous Syndrome

Cardiofaciocutaneous (CFC) syndrome, a rare genetic disorder, can be challenging to diagnose due to its overlapping phenotypes with other conditions. The main differential diagnoses for CFC syndrome include:

• Costello Syndrome (CS): This condition shares similar characteristics with CFC syndrome, such as cardiac abnormalities and distinctive craniofacial features [4]. However, CS is typically characterized by a more pronounced facial dysmorphism and a higher risk of tumors [3].
• Noonan Syndrome: Another RASopathy, Noonan syndrome can present with similar symptoms to CFC syndrome, including heart defects and skin abnormalities [2][5]. Genetic testing can help differentiate between the two conditions.

Key differences

While all three conditions share some similarities, there are distinct differences that can aid in diagnosis:

• Hair texture: CFC syndrome is typically characterized by unusually sparse, brittle, curly hair [3].
• Skin condition: Keratosis pilaris, a skin condition marked by rough, dry patches, is more commonly associated with CFC syndrome than CS or Noonan syndrome [1].

Genetic testing

Accurate diagnosis of CFC syndrome requires genetic testing to identify the specific gene mutation responsible for the condition. This can help rule out other differential diagnoses and confirm the presence of CFC syndrome.

References:

[1] Mar 28, 2022 [2] Jan 18, 2007 [3] Cardiofaciocutaneous (CFC) syndrome is one of the RASopathies and is a rare genetic disorder is typically characterized by unusually sparse, brittle, curly hair ... [4] Differential diagnoses include Costello Syndrome (CS) and Noonan Syndrome, which have overlapping phenotypes with CFC syndrome. CFC syndrome, unlike CS, does ... [5] Cardiofaciocutaneous (CFC) syndrome is characterized by cardiac abnormalities (pulmonic stenosis and other valve dysplasias, septal defects, ...