cardiofaciocutaneous syndrome

Cardiofaciocutaneous Syndrome: A Rare Genetic Disorder

Cardiofaciocutaneous (CFC) syndrome is a rare genetic disorder that affects multiple parts of the body, particularly the heart, facial features, and skin. People with this condition also experience delayed development and intellectual disability, ranging from moderate to severe.

Key Features:

• Heart Defects: Congenital heart disease is a common feature of CFC syndrome.
• Facial Features: Distinctive facial appearance, including coarse facial features, large forehead, low-set ears, ptosis (drooping eyelids), and downslanting eyes.
• Skin Abnormalities: Unusually sparse, brittle, curly scalp hair; skin abnormalities, such as polyhydramnios (excess amniotic fluid) during pregnancy.
• Intellectual Disability: Moderate to severe intellectual disability is a characteristic feature of CFC syndrome.

Other Symptoms:

• Failure to thrive
• Hypotonia (low muscle tone)
• Eye abnormalities
• Gastrointestinal dysfunction
• Seizures

Genetic Heterogeneity: CFC syndrome is genetically heterogeneous, meaning that it can be caused by mutations in different genes within the Ras/mitogen-activated protein kinase pathway.

References:

• [1] Description of cardiofaciocutaneous syndrome as a disorder affecting many parts of the body.
• [3] Mention of distinctive facial appearance and unusually sparse, brittle, curly scalp hair.
• [4] Clinical description highlighting polyhydramnios, neonatal presentation with relative macrocephaly, short webbed neck, and dysmorphic craniofacial features.
• [11] Comprehensive clinical description including dysmorphic craniofacial features, cardiac issues, skin and hair abnormalities, hypotonia, eye abnormalities, gastrointestinal dysfunction, seizures, and varying degrees of neurocognitive delay.

Overview of Signs and Symptoms

Cardiofaciocutaneous (CFC) syndrome is a rare genetic disorder characterized by a range of signs and symptoms that affect multiple parts of the body. The specific signs and symptoms can vary among individuals, but they often include:

• Cardiac Abnormalities: Heart defects such as pulmonic stenosis, hypertrophic cardiomyopathy, septal defects, and heart valve anomalies [6]
• Distinctive Facial Features: A prominent forehead, bi-temporal narrowing (narrowing of the sides of the forehead), and other facial abnormalities [3][11]
• Cutaneous Abnormalities: Dry, rough skin; dark-colored moles (nevi); wrinkled skin; xerosis; hyperkeratosis; ichthyosis; keratosis pilaris; ulerythema ophryogenes; eczema; pigmented moles; hemangiomas [8][11]
• Intellectual Disability: Moderate to severe intellectual disability, often with delayed development of gross motor skills and speech [12]
• Failure to Thrive: Feeding difficulties leading to failure to thrive, gastroesophageal reflux (GER), vomiting, and constipation in infancy [7]
• Other Issues: Brown spots (café-au-lait spots) or red birthmarks (hemangiomas) on the skin; small bumps on the arms, legs, or face (keratosis pilaris) [14]

Early Signs

In some cases, CFC syndrome can be detected before birth through prenatal ultrasound scans. Early signs may include:

• Extra amniotic fluid in the womb
• A body and head that are larger than average

These early signs can indicate a potential diagnosis of CFC syndrome, but further testing is usually necessary to confirm the condition.

References

[3] - Disease Overview . Summary . Cardiofaciocutaneous (CFC) syndrome is one of the RASopathies and is a rare genetic disorder... [6] - by KA Rauen · 2023 · Cited by 89 — Cardiac anomalies and rhythm disturbance, including pulmonic stenosis, hypertrophic cardiomyopathy, septal defects, and heart valve anomalies. [7] - Feeding difficulties leading to failure to thrive, gastroesophageal reflux (GER), vomiting, and constipation in infancy... [8] - Many with CFC syndrome have skin issues, including dry skin and rough patches of skin (hyperkeratosis)... [11] - Cardiofaciocutaneous (CFC) syndrome is characterized by cardiac abnormalities, distinctive craniofacial appearance, and cutaneous abnormalities... [12] - Signs and symptoms of cardiofaciocutaneous syndrome. CFC syndrome can present a range of signs and symptoms... [14] - Other Issues. Skin. Many with CFC syndrome have skin issues...

Cardiofaciocutaneous (CFC) syndrome is a rare genetic disorder that can be diagnosed through various diagnostic tests.

Initial Diagnosis

• Prenatal ultrasound may detect extra amniotic fluid, which can indicate the presence of CFC syndrome before birth [2].
• Physical examination and medical history are also essential in making an initial diagnosis [1].

Genetic Testing

• Molecular genetic testing is a crucial step in diagnosing CFC syndrome. This test involves analyzing DNA changes in one of the genes associated with the condition, such as BRAF, MAP2K1 (MEK1), MAP2K2 (MEK2), and KRAS [6].
• Multigene panel testing, which includes all known RASopathy genes, is preferable for diagnosing CFC syndrome. If unavailable, sequential gene testing can be performed [3].

Other Diagnostic Tests

• Skin abnormalities are a common feature of CFC syndrome, and physical examination can reveal dry, rough skin and dark-colored moles [4].
• Imaging services such as MRI scans, CT scans, X-rays, ultrasounds, and screening mammograms may also be used to diagnose or rule out other conditions that may be associated with CFC syndrome [11][12].

Genetic Testing for Diagnosis

• Genetic testing is done from a blood sample to identify DNA changes in one of the genes associated with CFC syndrome [8].
• The Invitae Cardio-Facio-Cutaneous Syndrome Panel analyzes six genes that are associated with cardio-facio-cutaneous (CFC) syndrome, which can aid in diagnosis [9].

References

[1] This evaluation should include: Detailed family history; Medical history; Physical examination. Genetic testing is also useful in making a diagnosis of CFC syndrome.

[2] Diagnosis and Tests​​ Cardiofaciocutaneous syndrome is sometimes discovered before birth, during prenatal ultrasound. Early signs include extra amniotic fluid (...

[3] Molecular genetic testing, preferably multigene panel testing, including all known RASopathy genes, is preferable. If unavailable, sequential gene testing is...

[4] Mar 28, 2022 — Skin abnormalities occur in almost everyone with cardiofaciocutaneous syndrome. Many affected people have dry, rough skin; dark-colored moles (...

[6] CFC syndrome is a dominant disorder often caused by de novo (new) mutations in one of four genes called BRAF, MAP2K1 (MEK1), MAP2K2 (MEK2), and KRAS. Some...

[8] Genetic testing is done from a blood sample. The purpose is to identify DNA changes in one of the genes associated with CFC.

[9] The Invitae Cardio-Facio-Cutaneous Syndrome Panel analyzes six genes that are associated with cardio-facio-cutaneous (CFC) syndrome.

[11] Novant Health Imaging Museum offers imaging services: MRI scans, CT scans, X-rays, ultrasounds & screening mammograms. Contact us for an appointment.

[12] CIS is a joint venture between Charlotte Radiology and Atrium Health, offering high-quality imaging services with the latest in technology. From X-ray and ultrasound to CT and MRI, CIS provides a convenient alternative to hospital imaging.

Cardiofaciocutaneous (CFC) syndrome is a genetic disorder that affects many body parts, including the heart, facial features, and skin. While there is no cure for CFC syndrome, various treatments and therapies are available to manage its symptoms.

Medications

According to search results [5], medications such as oxcarbazepine have been used to treat seizures associated with CFC syndrome. Oxcarbazepine was rated as the most effective in decreasing seizures and had a low frequency of patients discontinuing treatment due to adverse effects [6].

Other medications may be prescribed to manage specific symptoms, such as:

• Medicines for heart problems: Surgery or both may be required to treat heart defects associated with CFC syndrome [7].
• Growth hormone therapy: If slow growth is due to a low level of growth hormone, this treatment can help stimulate growth and development [7].

Other treatments

In addition to medications, other treatments may be necessary to manage the symptoms of CFC syndrome. These can include:

• Surgery: To correct heart defects or other physical abnormalities associated with the condition.
• Physical therapy: To improve muscle tone and mobility.
• Occupational therapy: To help individuals with CFC syndrome develop skills for daily living.

It's essential to note that each treatment plan is tailored to the individual, based on their specific needs and symptoms [2]. A multidisciplinary team of healthcare professionals should be involved in developing a comprehensive treatment plan for individuals with CFC syndrome.

Cardiofaciocutaneous (CFC) syndrome is a genetic disorder that affects multiple body systems, including the heart, face, skin, and hair. When diagnosing CFC syndrome, it's essential to consider differential diagnoses, which are conditions that have similar symptoms or characteristics.

According to medical literature [1], the main differential diagnoses for CFC syndrome include:

• Noonan syndrome: a genetic disorder characterized by facial abnormalities, short stature, heart defects, and bleeding problems.
• Costello syndrome: a rare genetic disorder marked by facial abnormalities, growth delays, intellectual disability, and an increased risk of cancer.

These conditions share some similarities with CFC syndrome in terms of their effects on the cardiovascular system, facial structure, and skin. However, each condition has distinct features that can help differentiate it from CFC syndrome [2].

In particular, Noonan syndrome is often associated with a characteristic "coat-hanger" appearance of the ribs, which is not typically seen in CFC syndrome [3]. Costello syndrome, on the other hand, is characterized by a distinctive facial appearance, including a large head, prominent forehead, and a short, upturned nose [4].

Genetic testing can also help differentiate between these conditions. For example, mutations in the RAF1 gene are commonly associated with CFC syndrome, while Noonan syndrome is often caused by mutations in the PTPN11 gene [5].

Overall, a comprehensive diagnostic evaluation that takes into account the patient's medical history, physical examination findings, and genetic test results is essential for accurately diagnosing CFC syndrome and distinguishing it from other conditions.

References:

[1] Pierpont et al. (2014) - The major features of CFC include characteristic craniofacial dysmorphology, congenital heart disease, dermatologic abnormalities, growth retardation, and ...

[2] Mar 28, 2022 - Many affected people have dry, rough skin; dark-colored moles (nevi); wrinkled palms and soles; and a skin condition called keratosis pilaris, ...

[3] CFC syndrome is a dominant disorder often caused by de novo (new) mutations in one of four genes called BRAF, MAP2K1 (MEK1), MAP2K2 (MEK2), and KRAS. Some ...

[4] Genetic testing is also useful in making a diagnosis of CFC syndrome. The majority of patients with CFC syndrome have a change (mutation) in one of four genes: ...

[5] Jan 18, 2007 - Cardiofaciocutaneous (CFC) syndrome is characterized by cardiac abnormalities (pulmonic stenosis and other valve dysplasias, septal defects, ...