UNDERSTANDING CARNEY COMPLEX: SYMPTOMS AND TREATMENT

Medically Reviewed by Dr. Sony Sherpa (MBBS)

Carney Complex is a rare inborn disorder that has a far-reaching impact on multiple body organs and systems. The development of benign tumors, skin changes, and endocrine abnormalities characterizes the condition, which was first described by Dr. J. Aidan Carney in 1985. There are only as few as 750 documented cases worldwide.

This article surveys the symptoms, causes, and treatment options for Carney Complex.

What is Carney Complex?

Carney Complex, a rare hereditary condition, affects multiple organs and systems in the body. It is sometimes referred to by related syndromes, including NAME (Nevi, Atrial Myxoma, Myxoid Neurofibromas, and Ephelides) syndrome and LAMB (Lentigines and Blue Nevi) syndrome, although these terms highlight specific features that may be present in individuals with Carney Complex.

The main causes are mutations in the PRKAR1A gene, which regulates cell growth and division. These mutations can develop benign tumors in various body parts, including the skin, heart, and endocrine glands.

What are the Symptoms of Carney Complex?

Symptoms can vary significantly from person to person, and not all individuals affected will experience the same symptoms.

NAME and LAMB are syndromes commonly occurring in those with Carney complex, often used interchangeably.

The hallmark features of each are discussed below.^[1]

NAME Syndrome

• Nevi (moles): Individuals with NAME syndrome often have numerous moles, typically larger and more numerous than average moles. While usually harmless, some may develop into melanoma, a serious form of skin cancer.
• Atrial Myxoma: These noncancerous tumors arise in the upper heart chamber (atrium). Myxomas can obstruct blood flow within the heart, resulting in shortness of breath, chest pain, heart palpitations, fatigue, and other cardiac manifestations. In some cases, they can also induce life-threatening events, such as heart failure or stroke.
• Myxoid Neurofibromas: These are tumors that affect the sheath surrounding nerves. They can develop anywhere on the body but most commonly occur in the head and neck area. Myxoid neurofibromas are usually painless and slow-growing, yet sometimes they can cause pain, numbness, or weakness depending on the affected nerve's location.
• Ephelides (freckles): People with NAME syndrome may have an abundance of freckles, appearing as small, light brown spots, typically on sun-exposed areas like the face, arms, and shoulders. Ephelides are benign and do not require treatment.

LAMB Syndrome

• Lentigines (freckles): Lentigines are a hallmark of LAMB syndrome, darker and more widespread than the ephelides seen in NAME syndrome. Lentigines typically appear on the face, hands, and forearms but can also involve other areas. Similar to ephelides, lentigines are benign and require no specific treatment.
• Blue Nevi: These deep-seated moles appear blue or black due to the presence of more profound pigment cells within the skin. Blue nevi are usually benign, but in rare instances, they can turn cancerous.

Skin symptoms of NAME and LAMB tend to fade when the individual reaches their 40s and as they age.

Regular consultations with a healthcare professional and appropriate screening measures are crucial for managing Carney complex and its associated complications.

Endocrine Abnormalities

Individuals may also experience abnormalities in their endocrine system, which is responsible for yielding hormones that govern all functions in the body. These abnormalities can lead to hormone-related issues, such as early puberty, irregular menstrual cycles, and infertility.

Other Signs

Other signs of Carney Complex may include^[2]:

• Large hands and feet (acromegaly), often due to excessive production of growth hormone by pituitary tumors, which are common in the condition
• Cushing's syndrome, which comprises excessive cortisol levels, weight gain, high blood pressure, and diabetes
• Thyroid nodules or tumors
• Adrenal gland tumors
• Breast tumors
• Testicular tumors

What Causes Carney Complex?

Carney Complex is the culmination of mutations in the PRKAR1A gene responsible for regulating cell growth and division. These mutations are inherited from a parent or acquired spontaneously during early development. In some cases, the cause may be unknown.

The PRKAR1A gene codes for the regulatory subunit (R1a) of the protein kinase A (PKA). PKA is a versatile enzyme that helps cells communicate with each other. It plays a prime role in cellular growth, energy production, cell death, and tissue renewal. When there are changes in the PRKAR1A gene, it can cause problems with how PKA works, leading to increased cell signaling, activation, growth, and carcinogenesis.^[3]

Many of the tumors found in those with Carney complex cause hormonal derangement that further contributes towards exacerbating symptoms, such as thyroid nodules, pituitary tumors, and breast or testicular tumors. These tumors can increase growth hormone levels, promote cellular growth, and elevate the metabolic rate.

Are Carney Complex Tumors Cancerous?

The tumors associated with the disorder are typically benign. However, in rare cases, these tumors can become cancerous, particularly if they are not detected and treated early on.

How is Carney Complex Diagnosed and Screened?

Diagnosing Carney Complex is challenging, as the symptoms are widespread and can vary greatly from person to person. The diagnosis can occur at any age, yet typically happens when the person is in their 20s.

Doctors will evaluate the patient based on the physical signs of the complex and the patient's medical history. Multiple freckles, moles, skin lesions, or tumors are often telling signs, particularly when coupled with high cortisol levels (Cushing's syndrome), heart enlargement, elevated growth hormone levels, growth factors, differences in thyroid hormones, increased levels of prolactin, and a history of tumors in the family.^[4]

If a doctor suspects Carney Complex, they may order various tests, including:

• Imaging tests, such as ultrasound, echocardiograms, MRI, or CT scans, to look for tumors in the body, heart enlargement, or other physical abnormalities.
• Blood tests to scan for hormonal abnormalities and to evaluate blood glucose levels.
• Urinary or salivary cortisol tests.
• Genetic testing to look for mutations in the PRKAR1A gene.

Screening for Carney Complex is recommended for individuals with a family history of the condition or those with a known mutation in the PRKAR1A gene. This may involve regular imaging tests and hormone tests to monitor for the development of tumors and endocrine abnormalities.

How is Carney Complex Treated and Managed?

There is currently no cure for Carney Complex, but there are various treatment options available to manage the symptoms and complications of this condition.^[5]

Treatment for Carney Complex typically involves a multidisciplinary approach, which may include:

Tumor Management

The treatment of associated tumors depends on their location, size, and potential for complications. In some cases, surgery is necessary to remove the tumor, while in others, a wait-and-see approach is best. In rare cases, radiation therapy or chemotherapy may be necessary.

Surgery

Surgery may assist some patients with the management of other complications that may arise, such as cardiac tumors or thyroid nodules. Standard procedures performed for those with the condition include:

• Open heart surgery to remove cardiac tumors. This surgery may need to be repeated as many heart tumors re-emerge.
• Transsphenoidal surgery to remove pituitary tumors.
• Removal of the testes or breasts if they produce excessive hormones.

In some cases, surgery is helpful with the removal of benign tumors that are causing symptoms or are at risk of becoming cancerous.

Hormone Therapy

Hormonal therapy, such as medications that regulate hormone levels, may be used to manage the endocrine abnormalities associated with Carney Complex.

Medications

Alongside hormone therapy, other medications can help to manage the symptoms. For example, medications can control high blood pressure, diabetes, or other related issues.

Supportive Care

It is essential to have a strong support system in place, as coping with the condition can be both physically and emotionally challenging. Supportive care may include psychotherapy, genetic counseling, member support groups, and other resources to help individuals cope with the challenges of this condition.

Living with Carney Complex

Dealing with Carney Complex can present many obstacles. Some lifestyle adjustments may be necessary, such as regular monitoring of hormone levels and imaging tests. However, with proper care and support, those affected can live long and healthy lives.

Sun protection is crucial to prevent excessive sun exposure that can worsen freckling, promote darkening, and increase skin cancer risk.

Latest Advancements in Carney Complex Research

Some of the latest developments in this field include^[6]:

• The designation of novel genes associated with Carney Complex may help improve diagnosis and treatment options.
• Finding new subtypes, such as a PKAR1A variation associated with liver lesions and complications.
• The development of new imaging techniques to detect tumors associated with Carney Complex.
• Better screening for Carney complex complications, including heart tumors or recurrence.
• The use of targeted therapies to treat tumors associated with this condition.

Conclusion

Carney Complex is a rare genetic disorder that creates widespread manifestations in multiple organs and systems in the body. Mutations in the PRKAR1A gene are the main causes and are characteristic of the development of benign tumors, skin changes, and endocrine abnormalities. While there is currently no cure for Carney Complex, various treatment options are available to manage the symptoms and complications of this condition. With proper management and support, individuals with Carney Complex can lead fulfilling lives.

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