What are the most common clinical presentations of Carney complex in females over 40 years old with facial involvement?

Clinical Presentations of Carney Complex in Females Over 40 with Facial Involvement

In females over 40 years old with facial Carney complex, the most common clinical presentations are spotty brown-to-black lentigines on the lips and conjunctiva, multiple blue nevi on the face, and cutaneous myxomas on the eyelids, with many patients also manifesting endocrine overactivity including Cushing's syndrome from primary pigmented nodular adrenocortical disease. 1, 2, 3

Primary Facial Cutaneous Manifestations

The hallmark facial features that persist and often become more prominent with age include:

• Spotty lentigines appear as pale brown to black pigmentation characteristically distributed on the lips (especially the vermilion border), conjunctiva (particularly the lacrimal caruncle and conjunctival semilunar fold), and inner/outer canthi 1, 3
• Multiple blue nevi occur on the face (though not typically on hands and feet), representing a major diagnostic criterion that distinguishes Carney complex from other conditions 1, 3
• Cutaneous myxomas present as soft tissue tumors with typical facial sites being the eyelids and external ear canal, and these lesions commonly recur after excision 1, 3
• The centrofacial area shows widespread lentiginous involvement that is a striking feature in the majority of patients 3, 4

Endocrine Manifestations in This Age Group

Females over 40 frequently present with endocrine overactivity that may have developed earlier but becomes clinically apparent or more severe:

• Cushing's syndrome caused by primary pigmented nodular adrenocortical disease is one of the most prevalent clinical manifestations, presenting with cushingoid features including facial changes 2, 3, 5
• Acromegaly from growth hormone-producing pituitary adenomas can manifest with characteristic facial coarsening 2, 3
• These endocrine features often correlate with the severity of dermatological signs—patients with prominent skin lesions tend to have more endocrine manifestations 4

Cardiac and Systemic Considerations

• Cardiac myxomas represent the most serious component of Carney complex and require systematic evaluation in all suspected cases, as they can develop at any age 2, 3, 6
• Breast myxomatosis and multiple ductal adenomas are additional manifestations that may be present in this age group 2

Phenotypic Heterogeneity Pattern

The clinical presentation shows significant heterogeneity even within the same age group:

• Approximately 75% of patients demonstrate lentiginosis, 43% have blue nevi, and 31% have cutaneous myxoma based on prospective data 4
• Patients can be classified into three phenotypic groups: those with no prominent skin lesions (approximately 19%), those with skin lesions not directly linkable to Carney complex (25%), and those with cutaneous lesions highly suggestive of Carney complex (56%) 4
• A correlation exists between dermatological phenotype and endocrine phenotype—patients with many facial and skin lesions typically have more endocrine signs 4

Critical Diagnostic Algorithm

When evaluating a female over 40 with facial involvement:

• First, systematically assess for the triad of spotty pigmentation on lips/conjunctiva/canthi, multiple blue nevi, and cutaneous myxomas on eyelids or external ear 1, 2
• Second, evaluate for cushingoid appearance or acromegalic facial features suggesting endocrine overactivity 2, 5
• Third, refer for genetic consultation when spotty skin pigmentation, cutaneous/mucosal myxoma, or epithelioid blue nevus is present PLUS one additional Carney complex criterion 1, 2
• Fourth, arrange cardiac evaluation with echocardiography to exclude cardiac myxomas, which remain a life-threatening risk at any age 2, 3

Key Clinical Pitfalls

• Do not dismiss facial lentigines as benign age-related pigmentation—Carney complex lentigines characteristically involve mucosal surfaces (lips, conjunctiva) which distinguishes them from solar lentigines 1
• Do not assume isolated facial findings exclude the diagnosis—at least 50% of individuals with isolated primary pigmented nodular adrenocortical disease have PRKAR1A mutations and may develop other manifestations later 1
• Do not overlook the recurrent nature of facial myxomas—these lesions commonly recur after excision and require ongoing surveillance 3