What are the typical skin manifestations and management of Carney Complex?

Carney Complex Skin Presentation

The hallmark skin manifestations of Carney Complex are spotty brown-to-black lentigines on the lips, conjunctiva, inner/outer canthi, and vaginal or penile mucosa, along with multiple blue nevi (including epithelioid blue nevi) and cutaneous/mucosal myxomas. 1

Primary Cutaneous Features

Pigmentary Abnormalities

• Lentigines appear as pale brown to black spotty pigmentation, characteristically distributed on the lips, conjunctiva, inner and outer canthi, and genital mucosa (vaginal or penile) 1
• These pigmented lesions are often the first clinical clue to the diagnosis and may be present from infancy 2, 3
• Blue nevi, including the epithelioid blue nevus subtype, occur as multiple lesions and represent a major diagnostic criterion 1, 2

Myxomatous Lesions

• Cutaneous and mucosal myxomas present as soft tissue tumors that can occur on skin and mucous membranes 1, 2
• These myxomas are distinct from cardiac myxomas but share similar histopathology 2, 4

Clinical Recognition Algorithm

When evaluating suspected Carney Complex, systematically assess for:

1. Spotty pigmentation on lips, conjunctiva, canthi, or genital mucosa (present in majority of cases) 1, 2
2. Multiple blue nevi anywhere on the body 1
3. Cutaneous myxomas on examination 1, 2
4. Associated endocrine features including cushingoid appearance or acromegalic features 1, 5, 2

Diagnostic Criteria and Genetic Referral

Refer for genetic consultation when:

• Spotty skin pigmentation is present PLUS one additional Carney complex criterion 1
• Cutaneous or mucosal myxoma is present PLUS one additional criterion 1
• Epithelioid blue nevus is present PLUS one additional criterion 1
• Two or more diagnostic criteria are met in the patient or first-degree relative 1

The American College of Medical Genetics and Genomics guidelines specify that PRKAR1A mutations are found in 71% of individuals with at least two major diagnostic criteria, making genetic testing highly informative in confirmed cases 1

Management of Skin Manifestations

Cutaneous lesions themselves typically require only observation and documentation, as they serve primarily as diagnostic markers rather than sources of morbidity 2, 4

However, the presence of skin findings mandates:

• Immediate cardiac evaluation with echocardiography to exclude cardiac myxomas, which require surgical removal and represent the most serious life-threatening manifestation 2, 4, 3
• Annual comprehensive screening for all manifestations starting in infancy, including endocrine evaluation for Cushing's syndrome (primary pigmented nodular adrenocortical disease), acromegaly, and thyroid/testicular tumors 2, 4
• Genetic counseling for the patient and first-degree relatives, as this is an autosomal dominant condition with nearly full penetrance 2, 4, 6

Critical Pitfalls to Avoid

Do not dismiss lentigines as benign freckles without considering the distribution pattern—Carney complex lentigines characteristically involve mucosal surfaces (lips, conjunctiva, genital mucosa), unlike common solar lentigines 1, 2, 3

Do not delay cardiac evaluation once skin findings suggest Carney Complex, as cardiac myxomas can cause sudden death from embolization or obstruction and may be present even in young patients 2, 4, 3

Do not assume isolated skin findings exclude the diagnosis—at least 50% of individuals with isolated primary pigmented nodular adrenocortical disease (Cushing's syndrome) have PRKAR1A mutations and may develop other manifestations later 1