Harvey Cushing Treated the First Known Patient With Carney Complex

Tsay, Cynthia; Stratakis, Constantine A.; Faucz, Fábio R.; London, Edra; Stathopoulou, Chaido; Allgäuer, Michael; Quezado, Martha; Dagradi, Terry; Spencer, Dennis D.; Lodish, Maya

doi:10.1210/js.2017-00283

Cited by 8 publications

(3 citation statements)

References 25 publications

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“…However, we performed similar studies in another patient, not included in this cohort because of age, and found LOH in tissue sample (unpublished information). Penetrance of CNC in PRKAR1A-positive cases is greater than 95% by the age of 50 years but at least two variants have been shown to result in incomplete penetrance (43). Typical CNC-related PAs are somatotroph, mixed GH/PRL-secreting adenomas or corticotropinomas, but PAs are very rarely the first manifestation of the syndrome (10,44).…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic characteristics in patients under 30 years with sporadic pituitary adenomas

Piscina

Najera

Rica

et al. 2021

European Journal of Endocrinology

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Objective: Pituitary adenomas (PA) are rare in young patients and additional studies are needed to fully understand their pathogenesis in this population. We describe the clinical and genetic characteristics of apparently sporadic PA in a cohort of young patients. Design: Clinical and molecular analysis of 235 patients (age ≤30 years) with a PA. Clinicians from several Spanish and Chilean hospitals provided data. Methods: Genetic screening was performed via next-generation sequencing and comparative genomic hybridization array. Clinical variables were compared among paediatric, adolescent (<19 years) and young adults’ (≥19-30 years) cohorts and types of adenomas. Phenotype-genotype associations were examined. Results: Among the total cohort mean age was 17.3 years. Local mass effect symptoms were present in 22.0% and prolactinomas were the most frequent (44.7%). Disease-causing germline variants were identified in 22 individuals (9.3%), more exactly in 13.1% and 4.7% of the populations aged 0-19 and 19-30 years, respectively; genetically positive patients were younger at diagnosis and had larger tumour size. Healthy family carriers were also identified. Conclusions: Variants in genes associated with syndromic forms of PAs were detected in a large cohort of apparently sporadic pituitary tumours. We have identified novel variants in well-known genes and set the possibility of incomplete disease penetrance in carriers of MEN1 alterations or a limited clinical expression of the syndrome. Despite the low penetrance observed, screening of AIP and MEN1 variants in young patients and relatives is of clinical value.

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Section: Discussionmentioning

confidence: 99%

Clinical and genetic characteristics in patients under 30 years with sporadic pituitary adenomas

Piscina

Najera

Rica

et al. 2021

European Journal of Endocrinology

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“…In 1985, one year after he described bilateral primary pigmented nodular adrenocortical disease (PPNAD) in four young patients with Cushing's syndrome (1), J A Carney, pathologist at the Mayo Clinic, described for the first time the 'complex of myxomas, spotty pigmentation and endocrine overactivity' (2), later named after him, based on a retrospective study of 40 patients. The 'Carney complex' (CNC) was consistent with some cases reported in the literature in the previous 4 years as 'NAME syndrome' (3) or 'LAMB syndrome' (4) (for naevi, atrial myxoma, myxoid neurofibromata and ephelides and lentigines, atrial myxoma, mucocutaneous myxomas and blue naevi, respectively), and probably consistent with a case of fatal bilateral atrial myxomas associated with 'many dark brown to black freckles on the skin, reported in 1960 (5); even evidence has been shown that Harvey Cushing treated the first known patient with Carney complex, more than 70 years before its first description (6).…”

Section: Introductionmentioning

confidence: 64%

MANAGEMENT OF ENDOCRINE DISEASE: Carney complex: clinical and genetic update 20 years after the identification of the CNC1 (PRKAR1A) gene

Bouys

Bertherat

2021

European Journal of Endocrinology

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Described for the first time in 1985, Carney complex (CNC) is a rare dominantly inherited multiple neoplasia syndrome with almost full penetrance, and characterized by both endocrine – primary pigmented nodular adrenocortical disease with Cushing’s syndrome, acromegaly and thyroid tumors – and non-endocrine manifestations such as cardiac, cutaneous and mucosal myxomas, pigmented cutaneous lesions, psammomatous melanotic schwannoma, osteochondromyxoma and a wide range of other tumors with potential malignancy. The pathophysiology of CNC is a model of dysregulation of the cAMP-PKA signalling in human diseases: as described twenty years ago, inactivating heterozygous mutations of PRKAR1A formerly known as CNC1, encoding the regulatory subunit 1α of protein kinase A are identified in more than 70% of the index cases, while inactivating mutations of genes encoding phosphodiesterases are found in rare and particular forms of the complex. There is at present no medical specific treatment for CNC, every confirmed or suspected CNC patient should be managed by a multidisciplinary team according to each manifestation of the disease and offered a long-term follow-up and genetic counselling. The better knowledge that we have now of this fascinating rare disease and its genetics will help to improve patients outcome.

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“…However, the first (now molecularly confirmed) CNC patient was reported by Professor Harvey Cushing in 1913. The patient presented acromegaly due to pituitary tumour, skin pigmentation and adrenal pathology [ 132 ]. The analysis of archive tissue revealed a PRKAR1A mutation.…”

Section: Germline Mutationsmentioning

confidence: 99%

Genetics of Acromegaly and Gigantism

Bogusławska

Korbonits

2021

JCM

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Growth hormone (GH)-secreting pituitary tumours represent the most genetically determined pituitary tumour type. This is true both for germline and somatic mutations. Germline mutations occur in several known genes (AIP, PRKAR1A, GPR101, GNAS, MEN1, CDKN1B, SDHx, MAX) as well as familial cases with currently unknown genes, while somatic mutations in GNAS are present in up to 40% of tumours. If the disease starts before the fusion of the epiphysis, then accelerated growth and increased final height, or gigantism, can develop, where a genetic background can be identified in half of the cases. Hereditary GH-secreting pituitary adenoma (PA) can manifest as isolated tumours, familial isolated pituitary adenoma (FIPA) including cases with AIP mutations or GPR101 duplications (X-linked acrogigantism, XLAG) or can be a part of systemic diseases like multiple endocrine neoplasia type 1 or type 4, McCune–Albright syndrome, Carney complex or phaeochromocytoma/paraganglioma-pituitary adenoma association. Family history and a search for associated syndromic manifestations can help to draw attention to genetic causes; many of these are now tested as part of gene panels. Identifying genetic mutations allows appropriate screening of associated comorbidities as well as finding affected family members before the clinical manifestation of the disease. This review focuses on germline and somatic mutations predisposing to acromegaly and gigantism.

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Harvey Cushing Treated the First Known Patient With Carney Complex

Cited by 8 publications

References 25 publications

Clinical and genetic characteristics in patients under 30 years with sporadic pituitary adenomas

Clinical and genetic characteristics in patients under 30 years with sporadic pituitary adenomas

MANAGEMENT OF ENDOCRINE DISEASE: Carney complex: clinical and genetic update 20 years after the identification of the CNC1 (PRKAR1A) gene

Genetics of Acromegaly and Gigantism

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