Carney complex

Not to be confused with Carney's triad.

Carney complex
Micrograph showing an atrial myxoma, a tumour seen in the Carney complex. H&E stain.

File:Carney complex with main associated diseases.png

Illustration of typical features seen in Carney complex.

Overview

Carney complex is an autosomal dominant genetic condition characterized by heart and skin myxomas, skin hyperpigmentation known as lentiginosis, and endocrine hyperactivity. Subsets of this condition include the LAMB syndrome and the NAME syndrome. Notably, Carney complex is separate from Carney's triad, despite the similarity in naming. Roughly 7% of cardiac myxomas are linked to Carney complex.

Clinical Presentation

The most noticeable clinical feature of Carney complex is the presence of spotty skin pigmentation and lentigines. These appear predominantly on facial regions including lips, eyelids, conjunctiva, and the oral mucosa. Cardiac myxomas associated with the complex can lead to severe complications such as embolic strokes and heart failure. Symptoms may include fever, joint pain, shortness of breath, a diastolic rumble, and a tumor plop sound. While the heart is a common site, myxomas can also manifest in the skin and breast. Endocrine tumors, on the other hand, may present with conditions like Cushing syndrome. The predominant endocrine gland manifestation in Carney complex is an ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD).

Subtypes

• LAMB syndrome: Denoted by the acronym LAMB, which stands for lentigines, atrial myxomas, and blue nevi.
• NAME syndrome: Represented by the acronym NAME, indicative of nevi, atrial myxoma, myxoid neurofibromas, and ephelides.

Furthermore, Carney syndrome is associated with testicular cancer, predominantly the Sertoli cell type. Cancers of the thyroid and pancreas have also been reported in association with the condition.

Pathophysiology

The most common cause of Carney complex is mutations in the PRKAR1A gene situated on chromosome 17 (17q23-q24). The protein encoded by this gene plays a crucial role as a type 1A regulatory subunit of protein kinase A and might act as a tumor-suppressor gene. Notably, around 70% of Carney complex patients show germline mutations in this gene.

A less frequent molecular pathogenesis involves genetic changes at chromosome 2 (2p16). Irrespective of these genetic differences, clinical manifestations appear consistent between PRKAR1A and chromosome 2p16 mutations.

Diagnosis

A definitive diagnosis of CNC (Carney complex) is established when a patient exhibits two or more major diagnostic criteria. It can also be diagnosed through the identification of a heterozygous germline pathogenic variant in PRKAR1A via molecular genetic testing.

Treatment

Surgical treatment of cardiac myxomas can be challenging due to the potential for tumor recurrence, often in a different location from the original tumor site within the heart.

Historical Context

The first potential mention of Carney complex dates back to 1914 when American neurosurgeon, Harvey Cushing, documented a case of a patient with a pituitary tumor. Post mortem results from this patient showed findings consistent with Carney complex, although the condition was yet to be formally identified. Recent investigations in 2017 subjected the archived tissue from Cushing's operation to DNA sequencing. The results revealed an Arg74His mutation in the PRKAR1A gene, solidifying a diagnosis of Carney complex. Consequently, Cushing's documentation seems to represent the earliest known account of this genetic condition.

See Also

• Myxoma
• Lentiginosis
• Cushing syndrome
• Endocrine hyperactivity
• Cardiac tumors
• Epithelioid blue nevus
• List of cutaneous neoplasms associated with systemic syndromes

External links

• GeneReview/UW/NIH entry on Carney complex