Carney Syndrome Clinical Presentation

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD   more...
 
Updated: Apr 17, 2012
 

History

Cutaneous manifestations are a major clue in the diagnosis of this condition. These manifestations include Cushing syndrome and skin changes associated with pigmentation. Subtle buccal and perioral lentigines may also be an important clue.[13]

Symptoms of Cushing syndrome may develop in young patients. The skin is fragile and thin. Patients bruise easily and heal poorly. The bones are weakened, and routine activities such as bending, lifting, or rising from a chair may lead to backaches and rib and spinal column fractures. Severe fatigue, muscle weakness, high blood pressure, and high blood sugar levels may be present. Irritability, anxiety, and depression are also common. Women may have menstrual periods that become irregular or stop. Men have decreased fertility with a diminished or absent desire for sex.

Symptoms of a prolactin-secreting tumor include hypogonadism (eg, amenorrhea, impotence) associated with symptoms of increased prolactin levels (eg, galactorrhea) in female patients.

Symptoms of acromegaly include headaches and visual abnormalities.

Symptoms of hyperparathyroidism include fatigue, anemia, muscle weakness, joint pain, constipation with nausea, frequent urination (sometimes bloody), mood change with confusion, abdominal pain due to ulcers, flank or back pain due to stones, bone pain due to bone erosions or fractures, and hypertension.

Atrial myxomas may create ball-valve obstructions that cause unexpected syncopal attacks, cardiac insufficiency, and sudden death in apparently healthy young children and adults.

Right-sided myxomas with extramedullary hematopoiesis and ossification in Carney complex has been described in a patient who also had a tiny eyelid cutaneous myxoma, multiple hypoechoic thyroid follicular adenomas, and multiple small testicular tumors.[14]

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Physical

Myxomas recur in approximately 12-22% of familial cases and in about 1-2% of sporadic cases.

Atrial myxomas

Upon physical examination, an accentuated first heart sound can be appreciated in patients with cardiac myxomas.

In adults, myxomas are the most common primary tumor of the heart. They arise in any of the 4 chambers or on the heart valves; however, about 90% are located in the atria. Myxomas in the atria have a left-to-right ratio of approximately 4:1.

Myxomas are mostly single and rarely multiple in several chambers.

Tumors can be 1-10 cm or larger in diameter.

The tumors can be sessile or pedunculated. In addition, the pedunculated form of atrial myxomas is often sufficiently mobile to move into or sometimes through the atrioventricular valves during diastole. Sometimes, such mobility exerts a wrecking-ball effect on the valve leaflets.

Multiple nevi, diffuse facial lentigines, and mucosal labial pigmentation

The classic presentation is a spotty pigmentation on the face, the chest and shoulders, and the vermilion border of the lips and conjunctiva.

The pigmentation can be tan or dark brown to black.

The lesions can be irregularly shaped or sharply delineated, and they can be small or several millimeters in diameter.

Subcutaneous myxoid neurofibromas and mammary fibroadenosis

Cutaneous myxomas have a predilection for the eyelids and external ear canals, although they may affect any part of the skin.

The mammary myxoid fibroadenomas in the complex are often multiple and bilateral; these fibroadenomas are an unusual finding in an otherwise normal breast.

Signs of acromegaly

  • Macroglossia may be present.
  • Prominent jaw and frontal bossing may be observed.
  • The patient may have large spadelike hands.
  • Skin tags may be observed.
  • Hyperhidrosis may occur.

Signs of Cushing syndrome

  • The skin is fragile and thin.
  • Patients bruise easily and heal poorly.
  • Purplish pink stretch marks are noted on the abdomen, thighs, buttocks, arms, and breasts.
  • Upper-body obesity, a rounded face, increased fat around the neck, and thin arms and legs are observed.
  • Children tend to be obese, with slowed growth rates.
  • Women usually have excessive hair growth on their face, neck, chest, abdomen, and thighs.

Endocrine involvement

Endocrine involvement in Carney complex also includes 3 types of testicular tumors: large-cell calcifying Sertoli-cell tumor (one of the rarest testicular neoplasms), adrenocortical rests, and Leydig-cell tumor.

These tumors appear with testicular masses, and about one third of affected male patients have them.

Large-cell calcifying Sertoli-cell tumors may also appear as bilateral masses. They can also secrete estrogens, resulting in precocious puberty, gynecomastia, or both.

As many as 75% of patients with Carney complex may have multiple thyroid nodules.

The nodules can appear as a goiter or thyroid mass when palpated on physical examination.

Patients can also present with symptoms of hyperthyroidism or hypothyroidism.

Psammomatous melanotic schwannoma most frequently occurs in the gastrointestinal tract (esophagus and stomach) and paraspinal sympathetic chain. Masses can be palpated on abdominal or paraspinal examination.

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Causes

Carney complex is inherited as an autosomal dominant trait, and the genes responsible have been mapped to bands 2p16 and 17q22-24.

Because the features of Carney complex, such as the paradoxical responses to endocrine signals, are similar to those of McCune-Albright syndrome and other conditions, the genes implicated in cyclic nucleotide-dependent signaling have been implicated.

Kirschner and colleagues examined families with Carney complex.[15] They first detected a loss of heterozygosity (LOH) in the vicinity of the PRKAR1A gene that encoded the protein kinase A regulatory subunit 1-alpha (R1alpha), which was mapped to chromosome 17q. They subsequently identified 3 unrelated kindreds with an identical mutation in the coding region of PRKAR1A. An analysis of PRKAR1A activity demonstrated that basal activity is decreased and cAMP-stimulated activity is increased in Carney complex tumors compared with non–Carney complex tumors. Kirschner et al concluded from these findings that germline mutations in PRKAR1A, an apparent tumor suppressor gene, are responsible for the Carney complex phenotype in a subset of patients with this disease.

Kirschner et al[16] also screened the mutations present in 54 Carney complex kindreds. In 14 of the mutations that were mapped to the PRKAR1A locus, they found a premature stop codon; one altered the initiator ATG codon. The messenger RNAs (mRNAs) resulting from this mutation were unstable, and they rapidly decayed. The PRKAR1A products were absent in the affected cells. These studies were the first to show a disease with mutations in the protein kinase A holoenzymes, critical components of the signaling pathway.

The role of PDE11A as a possible gene modifier of the phenotype was evaluated in a series of 150 patients with Carney complex. The high frequency of PDE11A variants identified implied that PDE11A may be a genetic modifying factor for the development of testicular and adrenal tumors in patients with germline PRKAR1A mutation.[17]

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Contributor Information and Disclosures
Author

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

Santiago A Centurion, MD  Staff Physician, Department of Dermatology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey

Santiago A Centurion, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, and Sigma Xi

Disclosure: Nothing to disclose.

Manuel A Cruz, MA  Adjunct Assistant Professor, Department of Pathology, UMDNJ-New Jersey Medical School

Manuel A Cruz, MA is a member of the following medical societies: Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

R Stan Taylor, MD  The JB Howell Professor in Melanoma Education and Detection, Departments of Dermatology and Plastic Surgery, Director, Skin Surgery and Oncology Clinic, University of Texas Southwestern Medical Center

R Stan Taylor, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery, American Dermatological Association, American Medical Association, American Society for Dermatologic Surgery, Christian Medical & Dental Society, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Christen M Mowad, MD  Associate Professor, Department of Dermatology, Geisinger Medical Center

Christen M Mowad, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Glen H Crawford, MD  Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital

Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD  Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology

Disclosure: Elsevier Royalty Other

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Ali Haider, MD, and Walter HC Burgdorf, MD, to the development and writing of this article.

References

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A pedunculated flesh-colored cutaneous myxoma that is 1.5 cm in diameter on trunk. Courtesy of Dermatology, NYU, and Ann Stoecker, medical photographer.
Polypoid neoplasm of fibrillary collagen and uniform stellate cells within abundant connective tissue mucin. Note telangiectasia and ramification of tumor as strands through a myxoid dermis (hematoxylin-eosin). Courtesy of Dermatology, NYU School of Medicine; photography by Anca Croitoru, MD, and Scott Sanders, MD.
 
 
 
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