What are the other Names for this Condition? (Also known as/Synonyms)

• Carvajal-Huerta Syndrome
• Keratoderma with Woolly Hair Type II (KWWH Type II)
• Woolly Hair-Palmoplantar Hyperkeratosis-Dilated Cardiomyopathy Syndrome

What is Carvajal Syndrome? (Definition/Background Information)

• Carvajal Syndrome may be described as a form of hereditary focal palmoplantar keratoderma that is transmitted in an autosomal recessive manner. The condition manifests during early infancy and is characterized by woolly hair (short and kinked hair) along-with dilated cardiomyopathy affecting the left ventricle. Thus, it is also known as Woolly Hair-Palmoplantar Hyperkeratosis-Dilated Cardiomyopathy Syndrome
• Hereditary focal palmoplantar keratoderma is a type of palmoplantar keratoderma (PPK) caused by genetic mutations. PPK is a benign skin condition, wherein there is thickening of skin (keratoderma) of the palms and/or soles. PPK is considered to be a pattern of skin findings and not a condition in itself. The abnormal skin thickening can be focal (localized), widespread (diffused), or punctate type (appearing as tiny bumps)
• Carvajal Syndrome is a cardio-cutaneous condition that presents both skin and heart related symptoms. Woolly hair and skin symptoms are observed in early childhood, while heart symptoms are observed usually in late childhood. This can lead to severe heart complications that may be fatal without early intervention
• Apart from addressing the skin presentations, managing, and treating dilated cardiomyopathy that causes the heart muscles to weaken is a priority. Depending on the severity, it may be treated with lifestyle changes, medications, non-surgical procedures, and through surgical implants. An early diagnosis is important to improve overall prognoses of individuals with Carvajal Syndrome

Who gets Carvajal Syndrome? (Age and Sex Distribution)

• Carvajal Syndrome is an extremely rare congenital disorder; the early signs and symptoms are noted in neonates and infants
• The condition affects both males and females
• Only a few cases are reported from South America (Ecuador) and Asia (India and Turkey)

What are the Risk Factors for Carvajal Syndrome? (Predisposing Factors)

• The risk factor for Carvajal Syndrome includes a positive family history of the condition
• Children born to consanguineous partners or spouses have a high risk for the condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Carvajal Syndrome? (Etiology)

• Carvajal Syndrome is caused by genetic abnormalities which are passed down (through families) in an autosomal recessive manner
• It is caused by mutations involving the DSP gene (at chromosome location 6p), which regulates the protein desmoplakin that is responsible for cell adhesion

Carvajal Syndrome is considered by some research experts as a variant of Naxos disease, another form of palmoplantar keratoderma.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents are carriers of the gene causing an autosomal recessive condition, there is a 25 % chance that a child will get the defective recessive gene from both parents. They will therefore have the disease.   If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of not receiving the gene from either parent, and will not have the disease and will not pass the gene on to their offspring. In the rare situation where both parents have the actual autosomal recessive condition, all their offspring will have two disease carrying genes and the disease is manifested.

What are the Signs and Symptoms of Carvajal Syndrome?

The signs and symptoms associated with Carvajal Syndrome may vary from one individual to another. It may be mild or severe and may include:

• Presence of woolly hair (coarse hair) at birth
• Development of small abnormally-thickened skin on the palms of the hands and soles, typically within the first year of birth
• These skin thickenings are mostly the “striate” type i.e., they are present as thick lines
• On the soles, the thickened areas are noted on the pressure points, such as on the toe mounds and heel
• It is often aggravated by physical activity (use of hands and fingers)
• The condition may be painful in some individuals, particularly keratoderma on the feet
• Formation of itchy skin blisters that may be temporary
• Skin lesions (follicular keratosis) may develop on the elbows, knees, and lower legs. Some may develop on the face and abdomen too
• Normal activities that involve the use of one’s hands and feet may be severely affected

Dilated cardiomyopathy may not be apparent during the initial years (early childhood), due to absence of any significant signs and symptoms; it is usually an incidental finding. Heart signs and symptoms, due to dilated cardiomyopathy, may be noted later during childhood. These may include:

• Chest pain
• Dizziness, fainting
• Shortness of breath
• Fatigue
• Palpitations
• Swelling of legs
• Clubbing of fingers also called nail cubbing

How is Carvajal Syndrome Diagnosed?

The diagnosis of Carvajal Syndrome may involve the following tests and procedures:

• A complete evaluation of medical history along with a thorough examination of the skin lesions by a dermatologist
• The healthcare provider may also ask many questions related to the individual’s age, family medical history, current medications, cosmetics, body lotions used, other medical conditions, infections, etc.
• Blood tests that may include complete blood count (CBC) test, basic metabolic panel, liver function test (LFT), and protein markers for heart disorders
• Dermoscopy: It is a diagnostic tool where a dermatologist examines the skin using a special magnified lens
• Wood’s lamp examination: In this procedure, the healthcare provider examines the skin using ultraviolet light. It is performed to examine the change in skin pigmentation
• Chest X-ray to check for heart size, contour, and fluid build-up in lungs
• Other imaging tests of the heart using techniques such as computed topography (CT) and magnetic resonance imaging (MRI) scans
• Electrocardiogram (EKG) to check the heart’s electrical activity
• Echocardiography (ECG or echo) uses sound waves to create a moving picture of the heart. This helps to check the size, shape, and pumping function of the heart
• Stress test: This test places stress on the heart by making it work harder and beat faster to determine, if the cardiac muscles can cope with the increased workload
• Molecular genetic testing to identify the gene involved
• Skin biopsy: A skin tissue biopsy is performed and sent to a laboratory for a pathological examination. The pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Carvajal Syndrome?

The complications associated with Carvajal Syndrome may include:

• Emotional stress
• Cosmetic concerns
• Disruption of normal life and activities if the condition is severe
• Heart related complications may include:
  • Heart valve regurgitation: It causes the heart to pump ineffectively, such that blood flows back into the heart
  • Arrhythmias: Abnormal heart rhythm, which can be triggered by physical exertion
  • Sudden cardiac arrest (which can be unexpected)
  • Embolism: Development of blood clots in the heart which may get into the bloodstream and obstruct blood supply to many important organs
  • Edema: Fluid build-up in the lungs, abdomen, legs, and feet
  • Congestive heart failure, which may be a medical emergency
• Treatment complications including a lack of treatment response

How is Carvajal Syndrome Treated?

There is no cure for Carvajal Syndrome. The condition is managed through symptomatic treatments, which may involve the following measures:

• Skin treatments may include:
  • Use of moisturizing creams and lotions; use of ointments containing vitamin D
  • Use of oral and systemic retinoids
  • Administration of keratolytics (medicine containing salicylic acid)
  • PUVA photochemotherapy
  • Surgical debridement (removal of thickened skin)
• Heart treatments for dilated cardiomyopathy may include:
  • Bringing about lifestyle changes including adhering to a healthy diet and engaging in routine physical activity
  • Prescription medications such as anti-arrhythmic medications, beta blockers, ACE inhibitors, digoxin, etc.
  • Surgical treatments may include implantation of automatic cardioverter defibrillator and heart transplantation (for terminal stages of the disorder)

Regular follow up visits with the healthcare provider is important and recommended.

How can Carvajal Syndrome be Prevented?

Currently, Carvajal Syndrome is a genetic disorder that cannot be prevented. However, the following may be considered:

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited genetic disorders such as hereditary palmoplantar keratoderma

What is the Prognosis of Carvajal Syndrome? (Outcomes/Resolutions)

The prognosis of Carvajal Syndrome may vary from one individual to another and is dependent on the severity of the condition.

• An early detection of the heart abnormality (dilated cardiomyopathy) can ensure prompt intervention and minimised risk for mortalities
• Unrecognised dilated cardiomyopathy may rarely lead to sudden death due to congestive heart failure (typically in adolescence)

Additional and Relevant Useful Information for Carvajal Syndrome:

Cleaning the skin too hard with strong chemicals or soaps may aggravate the skin condition. Care must be taken avoid strong soaps and chemicals that could potentially worsen the condition.