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. Author manuscript; available in PMC: 2016 Jul 1.
Published in final edited form as: Eur J Endocrinol. 2015 Jun 30;173(4):M85–M97. doi: 10.1530/EJE-15-0209

Table 2.

Diagnostic criteria for CNC*

Major Criteria

  1. Spotty skin pigmentation with typical distribution (lips, conjunctiva and inner or outer canthi, vaginal and penile mucosal)

  2. Myxoma** (cutaneous and mucosal) or cardiac myxoma**

  3. Breast myxomatosis** or fat-suppressed magnetic resonance imaging findings suggestive of this diagnosis

  4. PPNAD** or paradoxical positive response of urinary glucocorticosteroid excretion to dexamethasone administration during Liddle’s test

  5. Acromegaly as a result of growth hormone (GH)-producing adenoma*

  6. LCCSCT** or characteristic calcification on testicular ultrasound

  7. Thyroid carcinoma*(at any age) or multiple hypoechoic nodules on thyroid ultrasound in prepubertal child

  8. Psammomatous melanotic schwannomas (PMS)**

  9. Blue nevus, epithelioid blue nevus (multiple)**

  10. Breast ductal adenoma (multiple)**

  11. Osteochondromyxoma**

Supplemental criteria

  1. Affected first-degree relative

  2. Activating pathogenic variants of PRKACA (single base substitutions and copy number variation) and PRKACB (Beuschlein, Fassnacht et al. 2014, Forlino, Vetro et al. 2014)

  3. Inactivating mutation of the PRKAR1A gene (Bossis, Voutetakis et al. 2004)

Findings suggestive of or possibly associated with CNC, but not diagnostic for the disease (minor criteria)

  1. Intense freckling (without darkly pigmented spots or typical distribution)

  2. Blue nevus, common type (if multiple)

  3. Café-au-lait spots or other ‘birthmarks’

  4. Elevated IGF-I levels, abnormal glucose tolerance test (GTT), or paradoxical GH response to TRH (thyrotropin-releasing hormone) testing in the absence of clinical acromegaly

  5. Cardiomyopathy

  6. History of Cushing’s syndrome, acromegaly, or sudden death in extended family

  7. Pilonidal sinus

  8. Colonic polyps (usually in association with acromegaly)

  9. Multiple skin tags or other skin lesions; lipomas

  10. Hyperprolactinemia (usually mild and almost always combined with clinical or subclinical acromegaly)

  11. Single, benign thyroid nodule in a child younger than age 18 years; multiple thyroid nodules in an individual older than age 18 years (detected on ultrasound examination)

  12. Family history of carcinoma, in particular of the thyroid, colon, pancreas, and ovary; other multiple benign or malignant tumors

*

To make the diagnosis of CNC, a patient must either: (1) exhibit two of the major criteria confirmed by histology, imaging or biochemical testing or meet (2) one major criterion and one supplemental one

**

with histologic confirmation