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Carney complex - Skin
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Carney complex - Skin

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Contributors: Chris G. Adigun MD, David Dasher MD, Jeffrey D. Bernhard MD, Sarah Stein MD, Karen Wiss MD, Sheila Galbraith MD, Craig N. Burkhart MD, Dean Morrell MD, Lynn Garfunkel MD, Nancy Esterly MD
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Synopsis

NAME is a syndrome that includes nevi, atrial myxomas, myxoid neurofibromatosis, ephelides, and endocrine neoplasia. LAMB syndrome, an acronym for lentigines, atrial myxomas, mucocutaneous myxomas, and blue nevi, shares many features with NAME syndrome, including abnormalities of pigmentation, endocrine overactivity, and cutaneous and/or visceral myxomas. More current analysis of these disorders has categorized them as part of the Carney complex (CNC). CNC is a multiple neoplasia syndrome characterized by dermatologic findings of lentigines, blue nevi, café-au-lait spots, and cutaneous tumors such as myxomas and fibromas. CNC is caused by an inactivating mutation of the PRKAR1A gene, and is inherited in an autosomal dominant pattern. There appears to be genetic heterogeneity, however, with mutations in this gene found in roughly half of affected patients.

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
Other common cutaneous findings in CNC that are not diagnostic criteria but are suggestive of the diagnosis include intense freckling, café-au-lait spots, multiple fibrous tumors, lipomas, and angiofibromas.

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.

Codes

ICD10CM:
Q84.8 – Other specified congenital malformations of integument

SNOMEDCT:
239132009 – LAMB - Lentigines, atrial myxoma, mucocutaneous myoma, blue nevus syndrome

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Differential Diagnosis & Pitfalls

Syndromes with lentigines as a prominent finding:
  • 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.
Other possibilities that may mimic lentiginosis:
  • 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.
In older patients:
  • Solar lentigo – Typically occurs on sun-exposed surfaces with increasing age and is less regular in appearance
  • An oral mucosal dark macule may be difficult to distinguish from an amalgam tattoo.

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Last Updated: 03/29/2017
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Carney complex : Hyperpigmented macule
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