- Skin pigmentary abnormalities: multiple lentigines of the face
- Myxoma: Cardiac myxoma (usually pedunculated friable gelatinous tumors arising from endocardial surface). Multiple tumors affecting any or all chambers. Cutaneous myxoma predominantely at the eyelid, at mucosal-epithelial junctions, external ear canal, nipple and external genital. Breast myxomas and osteochondromyxoma
- Schwannoma: psammomatous melanotic schwannoma (PMS), nerve sheath tumors typically with heavy pigmentation (melanin), frequent calcification and multicentric.
- Endocrine tumors/ overactivity: primary pigmented nodular disease (PPND)or adrenocortical overactivity, growth hormone producing pituitary adenoma or excess of GH production or acromegaly, Large-cell calcifying Sertoli cell tumors (LCCSCT) or characteristic microcalcification or suspect testicular ultrasonography , thyroid adenoma or carcinoma (papillary or follicular).
Carney Complex - PRKAR1A
Clinical Features
The clinical features of Carney Complex (CNC) are lentigines, myxomas, endocrine tumors and schwannomas. The most common clinical presenting features are pale brown to black lentigines which typically increase in number at puberty. Myxomas of the heart (seen in about 72% of all patients) occur at ayoung age. Other localisations of myxomas are the skin, breast oropharynx, bones and female genital tract. Approximately 25% of CNC patients show primary pigmented nodular adrenocortical disease (PPNAD) causing cushing syndrome. Additional tumors are Large-cell calcifying Sertoli cell tumors (LCCSCTs) and thyroid adenomas. About 10% of CNC patients have a psammomatous melanotic schwannoma (PMS), a rare tumor of the nerve sheath. The median age of diagnosis is 20 years.
CNC needs to be differentiated from Carney syndrome (Carney triad), which occurs with the triad of gastric leiomyosarcoma, pulmonary chondroma and paraganglioma.
Genetic Information
CNC is an autosomal dominant inherited disease. Approximately 55% of all CNC patients have germ line mutations in the PRKAR1A gene (70% have an affected parent; 30% are de novo mutations). The penetrance is 70-80% by age 40 years.
PRKAR1A gene has 10 exons and encodes cAMP-dependent protein kinase type I-alpha regulatory subunit which is an important molecule in many endocrine signalling pathways. Another CNC-gene is mapped to region 2q16.
Diagnostic
Indication
Method
All exons in the PRKAR1A gene as well as their flanking regions are analysed using DNA sequencing.
Sample Requirement
2 - 4 ml of EDTA blood
Duration
2 - 3 weeks