Carney complex and its subsets LAMB syndrome and NAME syndrome are

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

conditions comprising

myxoma A myxoma (New Latin from Greek 'muxa' for mucus) is a myxoid tumor of primitive connective tissue. It is most commonly found in the heart (and is the most common primary tumor of the heart in adults) but can also occur in other locations. Ty ...

s of the heart and skin, hyperpigmentation of the skin (

lentiginosis Lentiginosis refers to the presence of lentigines in large numbers or in a distinctive configuration. These are spotted areas created by accumulation in the skin due to sun exposure. Due to a high irregularity any distinction from randomness defin ...

), and

endocrine The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...

overactivity. It is distinct from

Carney's triad Carney triad (CT) is characterized by the coexistence of three types of neoplasms, mainly in young women,OMIM - Online Mendelian Inheritance in Man. Carney Triad (OMIM 604287/ref> including gastric gastrointestinal stromal tumor, pulmonary chondr ...

. Approximately 7% of all cardiac myxomas are associated with Carney complex.

Presentation

The spotty skin pigmentation and lentigines occur most commonly on the face, especially on the lips, eyelids,

conjunctiva The conjunctiva is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the eye). It is composed of non-keratinized, stratified squamous epithelium with goblet cells, stratified columnar epithelium ...

and oral mucosa. Cardiac myxomas may lead to embolic strokes and

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

and may present with fever, joint pain, shortness of breath, diastolic rumble and tumor plop. Myxomas may also occur outside the heart, usually in the skin and breast. Endocrine tumors may manifest as disorders such as

Cushing syndrome Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a ...

. The most common

endocrine gland Endocrine glands are ductless glands of the endocrine system that secrete their products, hormones, directly into the blood. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid ...

manifestation is an ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). The LAMB

acronym An acronym is a word or name formed from the initial components of a longer name or phrase. Acronyms are usually formed from the initial letters of words, as in ''NATO'' (''North Atlantic Treaty Organization''), but sometimes use syllables, as ...

refers to

lentigines A lentigo () (plural lentigines, ) is a small pigmented spot on the skin with a clearly defined edge, surrounded by normal-appearing skin. It is a harmless (benign) hyperplasia of melanocytes which is linear in its spread. This means the hyperplasi ...

atrial The atrium ( la, ātrium, , entry hall) is one of two upper chambers in the heart that receives blood from the circulatory system. The blood in the atria is pumped into the heart ventricles through the atrioventricular valves. There are two at ...

s, and blue nevi. NAME refers to

nevi Nevus (plural nevi) is a nonspecific medical term for a visible, circumscribed, chronic lesion of the skin or mucosa. The term originates from ''nævus'', which is Latin for "birthmark"; however, a nevus can be either congenital (present at bir ...

, atrial myxoma, myxoid neurofibromas, and

ephelides Freckles are clusters of concentrated melaninized cells which are most easily visible on people with a fair complexion. Freckles do not have an increased number of the melanin-producing cells, or melanocytes, but instead have melanocytes that ...

. Testicular cancer, particularly

Sertoli cell Sertoli cells are a type of sustentacular "nurse" cell found in human testes which contribute to the process of spermatogenesis (the production of sperm) as a structural component of the seminiferous tubules. They are activated by follicle-stimul ...

type, is associated with Carney syndrome. Thyroid and pancreas cancer may also occur. Although J Aidan Carney also described

it is entirely different.

Pathophysiology

Carney complex is most commonly caused by mutations in the

PRKAR1A cAMP-dependent protein kinase type I-alpha regulatory subunit is an enzyme that in humans is encoded by the ''PRKAR1A'' gene. Function cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by acti ...

gene on

chromosome 17 Chromosome 17 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 17 spans more than 83 million base pairs (the building material of DNA) and represents between 2.5 and 3% of the total D ...

(17q23-q24) which may function as a tumor-suppressor gene. The encoded protein is a type 1A regulatory subunit of protein kinase A. Inactivating germline mutations of this gene are found in 70% of people with Carney complex. Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at

chromosome 2 Chromosome 2 is one of the twenty-three pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs and representing almost e ...

(2p16). Both types of Carney complex are

. Despite dissimilar genetics, there appears to be no

phenotypic In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

difference between PRKAR1A and chromosome 2p16 mutations.

Treatment

Cardiac myxomas can be difficult to manage surgically because of recurrence within the heart, often far away from the site of the initial tumor.

History

In 1914 an American neurosurgeon,

Harvey Cushing Harvey Williams Cushing (April 8, 1869 – October 7, 1939) was an American neurosurgeon, pathologist, writer, and draftsman. A pioneer of brain surgery, he was the first exclusive neurosurgeon and the first person to describe Cushing's disease. ...

, reported on a patient with a pituitary tumour on whom he had operated.Tsay CJ, Stratakis CA, Faucz FR, London E, Stathopoulou C, Allgauer M, Quezado M, Dagradi T, Spencer DD, Lodish M (2017) Harvey Cushing treated the first known patient with Carney complex. J Endocr Soc 1(10):1312-1321. doi: 10.1210/js.2017-00283 The post mortem findings as reported were consistent with Carney complex, though at the time this condition had yet to be described. In 2017 archived tissue from the operation in Cushing's report was subjected to DNA sequencing, revealing an Arg74His (

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the de ...

guanine Guanine () ( symbol G or Gua) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine (uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside is called ...

(G)->

adenosine Adenosine ( symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building ...

(A) transition in the second

codon The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...

position of the 74th codon in the protein) mutation in the PRKAR1A gene, confirming a diagnosis of Carney complex. Therefore, Cushing's paper appears to be the first report of this complex.

References

External links