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 Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

conditions comprising

myxoma A myxoma (New Latin from Ancient Greek, Greek '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 ...

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 define ...

), and

endocrine The endocrine system is a messenger system in an organism comprising feedback loops of hormones that are released by internal glands directly into the circulatory system and that target and regulate distant organs. In vertebrates, the hypotha ...

overactivity. It is distinct from Carney triad. 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 In the anatomy of the eye, the conjunctiva (: conjunctivae) 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 gobl ...

and oral mucosa.

Cardiac myxoma A myxoma is a rare benign tumor of the heart. Myxomata are the most common primary cardiac tumor in adults, and are most commonly found within the left atrium near the valve of the fossa ovalis. Myxoma may also develop in the other heart chambers. ...

s may lead to embolic strokes and

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

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 The endocrine system is a network of glands and organs located throughout the body. Along with the nervous system, it makes the neuroendocrine system, which controls and regulates many of the body's functions. Endocrine glands are ductless gland ...

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

acronym An acronym is a type of abbreviation consisting of a phrase whose only pronounced elements are the initial letters or initial sounds of words inside that phrase. Acronyms are often spelled with the initial Letter (alphabet), letter of each wor ...

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 hyperpl ...

atrial The atrium (; : atria) is one of the 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 mitral and tricuspid heart valves. ...

s, and blue nevi. NAME refers to

nevi The Infrastructure Investment and Jobs Act (IIJA), also known as the Bipartisan Infrastructure Law (BIL),H.R. 3684 is a United States federal statute enacted by the 117th United States Congress and signed into law by President Joe Biden on Nove ...

, atrial myxoma, myxoid neurofibromas, and ephelides. 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-sti ...

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

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 chond ...

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 act ...

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 84 million base pairs (the building material of DNA) and represents between 2.5 and 3% of the total DN ...

(17q23-q24) which may function as a

tumor-suppressor gene A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or red ...

. The encoded protein is a type 1A regulatory subunit of protein kinase A. Inactivating

germline mutation A germline mutation, or germinal mutation, is any detectable variation within germ cells (cells that, when fully developed, become sperm and Egg cell, ova). Mutations in these cells are the only mutations that can be passed on to offspring, when e ...

s 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 ei ...

(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 (physical form and structure), its developmental processes, its biochemical and physiological propert ...

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 neurosurgery, neurosurgeon, pathologist, writer, and draftsman. A pioneer of brain surgery, he was the first exclusive neurosurgeon and the first person to describe Cush ...

, reported on a patient with a pituitary tumour on whom he had operated. 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 guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...

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

guanine Guanine () (symbol G or Gua) is one of the four main nucleotide bases 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 ...

(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 build ...

(A) transition in the second

codon Genetic code is a 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 prote ...

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