Carney complex - Skin
By early adulthood, patients with CNC may have life-threatening complications as a consequence of cardiac myxomas and/or endocrine abnormalities. Diagnostic cutaneous findings are present in over half of CNC patients, and cutaneous findings at least suggestive of CNC are present in 80%. Most importantly, these cutaneous features present at a young age. Cutaneous manifestations thus can be used for early detection of the disease, and may prevent its most dangerous complications.
A diagnosis of CNC is given when two or more major criteria are met. Cutaneous manifestations of CNC comprise three of the major criteria, which include the following:
- Spotty skin pigmentation in the characteristic distribution, involving the lips, conjunctiva, inner or outer canthi, and genital mucosa
- Cutaneous or mucosa myxoma
- Multiple blue nevi or an epithelioid blue nevus
Lentiginosis is one of the earliest clinically detectable signs of CNC. Lentigines generally occur by the peripubertal period, but may be present at birth. They are not associated with sun exposure. The characteristic distribution is the centrofacial area, vermilion border, and conjunctiva. Intra-oral and genital lentigines are also commonly found. These lentigines may fade after the fourth decade of life. They differ from the common freckles in that there is actual hyperplasia of melanocytes, whereas freckles have normal numbers of melanocytes that produce increased pigment. Lentigines found on mucous membranes can be deeply pigmented, rather large, and have irregular borders.
Blue nevi in CNC are typically small and multiple. They often occur on the face, trunk, limbs, and less commonly, hands and feet. Café-au-lait spots are usually present, and may be present from birth. Myxomas tend to occur by age 18, are often multiple in number, and have a tendency to recur if surgically excised.
The myxomas present in CNC may involve the heart, skin, and breasts. It is critical that these patients have regular cardiac screening, as cardiac myxomas account for 20% of the deaths of these patients. These cardiac myxomas are usually located in the atria, and are commonly bilateral. Early surgical resection may be lifesaving, mandating the regular screening.
Systemic findings of diagnostic value to CNC include cardiac myxoma, breast myxomatosis, paradoxical positive response of urinary glucocorticosteroid excretion to dexamethasone administration, acromegaly from GH-producing tumor, characteristic calcification on testicular ultrasound, multiple hypoechoic nodules on thyroid ultrasound in a young patient or thyroid carcinoma, psammomatous melanotic schwannoma, breast ductal adenoma, and osteochondromyxoma.
For more information on type 1, see OMIM.
For more information on type 2, see OMIM.
Q84.8 – Other specified congenital malformations of integument
239132009 – LAMB - Lentigines, atrial myxoma, mucocutaneous myoma, blue nevus syndrome
- McCune Albright syndrome – Characterized by poly/monostotic fibrous dysplasia, CALMs, and hyperfunctioning endocrinopathies.
- LEOPARD syndrome – Characterized by multiple lentigines, ECG conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, deafness. Allelic mutations to Noonan's syndrome.
- Peutz-Jeghers syndrome (PJS) – Characterized by lentigines (perioral and oral), multiple gastrointestinal polyps, and visceral tumors (pancreas, ovary, testes).
- Cronkhite-Canada syndrome – Characterized by lentigines (buccal mucosa, face, palmoplantar), alopecia, nail dystrophy, and intestinal polyps.
- Noonan syndrome – Characterized by a webbed neck, hypertelorism, short stature, undescended testicles, low posterior hairline, cardiovascular anomalies, lymphedema, dystrophic nails, and curly hair. Allelic mutations to LEOPARD.
- Touraine centrofacial lentiginosis – Characterized by lentigines (central face and lips, spares mucosa, none elsewhere), bone abnormalities, dysraphia, endocrine disorders, neurologic disease.
- Inherited patterned lentiginosis – Characterized by lentigines (central face, hands, feet, buttocks, spares mucous membranes); no other associated systemic abnormalities. Occurs in African Americans.
- Segmental and agminated lentiginosis – May have no associated systemic manifestations.
- Generalized lentigines
- Arterial dissection with lentiginosis
- Laugier-Hunziker syndrome – Characterized by pigmentation of the nails associated with buccal and lip hyperpigmentation.
- Cantú (hyperkeratosis-hyperpigmentation) syndrome – Characterized by hypertrichosis, osteochondrodysplasia, and cardiomegaly.
- Cowden disease – Characterized by multiple facial trichilemmomas, oral mucosal papillomas, and acral keratotic papules. Allelic mutations to Bannayan-Riley-Ruvalcaba syndrome.
- Bannayan-Riley-Ruvalcaba syndrome – Characterized by multiple subcutaneous lipomas and vascular malformations, lentigines of the penis and vulva, verrucae, and acanthosis nigricans. Allelic mutations to Cowden syndrome.
- Nevus spilus – Appears as a circumscribed patch of light brown hyperpigmentation with smaller, darker pigmented macules or papules within the patch.
- Numerous centrofacial lentigines in an African American are likely attributable to inherited patterned lentiginosis. This is a benign disorder that is inherited as an autosomal dominant trait, and thus patients should have a positive family history.