Carney complex is an autosomal dominant multiple neoplasia syndrome defined by the combination of spotty skin pigmentation (lentigines and blue naevi), cardiac and extracardiac myxomas, endocrine overactivity, and psammomatous melanotic schwannoma. Most cases are caused by germline inactivating variants in PRKAR1A at 17q22-24, encoding the type I-alpha regulatory subunit (RIalpha) of protein kinase A; a second locus at 2p16 accounts for the remainder. Mechanistically the syndrome is a tumor suppressor two-hit disorder in which the suppressor is a brake on a second-messenger pathway rather than on the cell cycle. RIalpha binds and inhibits the PKA catalytic subunits until cyclic AMP displaces it; losing RIalpha therefore does not raise basal kinase activity so much as remove the restraint on cAMP-stimulated activity, and this is what measurement in Carney complex tumours shows — decreased basal PKA activity but increased cAMP-stimulated activity relative to non-Carney tumours. That signature explains the syndrome's most distinctive clinical trait, the paradoxical responses to endocrine signals seen in primary pigmented nodular adrenocortical disease, where dexamethasone raises rather than suppresses cortisol. Two-hit architecture is directly evidenced: loss of heterozygosity in the vicinity of PRKAR1A in 17q-linked families is what localized the gene. Cardiac myxoma is the principal cause of death and can occur at any age and in any chamber, which drives lifelong echocardiographic surveillance.
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name: Carney Complex
creation_date: "2026-08-23T00:00:00Z"
category: Mendelian
categories:
- Hereditary Cancer Syndrome
- Cancer Predisposition Syndrome
- Endocrine Neoplasia
parents:
- hereditary cancer-predisposing syndrome
disease_term:
preferred_term: Carney complex
term:
id: MONDO:0015285
label: Carney complex
synonyms:
- CNC
- LAMB syndrome
- NAME syndrome
- Carney syndrome
description: >-
Carney complex is an autosomal dominant multiple neoplasia syndrome defined by
the combination of spotty skin pigmentation (lentigines and blue naevi),
cardiac and extracardiac myxomas, endocrine overactivity, and psammomatous
melanotic schwannoma. Most cases are caused by germline inactivating variants
in PRKAR1A at 17q22-24, encoding the type I-alpha regulatory subunit (RIalpha)
of protein kinase A; a second locus at 2p16 accounts for the remainder.
Mechanistically the syndrome is a tumor suppressor two-hit disorder in which
the suppressor is a brake on a second-messenger pathway rather than on the cell
cycle. RIalpha binds and inhibits the PKA catalytic subunits until cyclic AMP
displaces it; losing RIalpha therefore does not raise basal kinase activity so
much as remove the restraint on cAMP-stimulated activity, and this is what
measurement in Carney complex tumours shows — decreased basal PKA activity but
increased cAMP-stimulated activity relative to non-Carney tumours. That
signature explains the syndrome's most distinctive clinical trait, the
paradoxical responses to endocrine signals seen in primary pigmented nodular
adrenocortical disease, where dexamethasone raises rather than suppresses
cortisol. Two-hit architecture is directly evidenced: loss of heterozygosity
in the vicinity of PRKAR1A in 17q-linked families is what localized the gene.
Cardiac myxoma is the principal cause of death and can occur at any age and in
any chamber, which drives lifelong echocardiographic surveillance.
inheritance:
- name: Autosomal dominant
inheritance_term:
preferred_term: Autosomal dominant inheritance
term:
id: HP:0000006
label: Autosomal dominant inheritance
penetrance: INCOMPLETE
expressivity: VARIABLE
description: >-
Carney complex is inherited as an autosomal dominant trait with variable
expressivity: which components of the complex appear differs between
families and between affected members of one family, and at least two loci
are involved. Sporadic cases arising from de novo variants are well
documented.
evidence:
- reference: PMID:10973256
reference_title: Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
CNC is inherited as an autosomal dominant trait and the genes responsible
have been mapped to 2p16 and 17q22-24 (refs 6, 7).
explanation: >-
States the inheritance pattern and the genetic heterogeneity of the
syndrome.
- reference: PMID:20301463
reference_title: "Carney Complex."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Approximately 70% of individuals diagnosed with CNC have an affected
parent; approximately 30% have a de novo pathogenic variant.
explanation: >-
GeneReviews Genetic Counseling section. The de novo rate is high enough
that a negative family history carries little weight against the
diagnosis. Evidence source is OTHER because GeneReviews is an
expert-authored review rather than a primary study.
- reference: PMID:20301463
reference_title: "Carney Complex."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Each child of an individual with CNC has a 50% chance of inheriting the
pathogenic variant.
explanation: >-
GeneReviews Genetic Counseling section: the transmission risk to
offspring.
pathophysiology:
- name: Germline PRKAR1A First-Hit Inactivation
conforms_to: "germline_two_hit_tumor_predisposition#Constitutional First-Hit Tumor Suppressor Inactivation"
description: >-
A heterozygous inactivating variant in PRKAR1A, encoding the PKA type I-alpha
regulatory subunit RIalpha, is present constitutionally. Candidate-gene
reasoning arrived at cyclic-nucleotide signalling before the gene was found,
from the syndrome's resemblance to McCune-Albright syndrome and from its
paradoxical endocrine responses. An identical coding-region variant was found
in three unrelated kindreds and again in a sporadic case, with distinct
variants in further families including one with isolated inherited cardiac
myxomas.
role: trigger
biological_scale: MOLECULAR
gene:
preferred_term: PRKAR1A
modifier: DECREASED
term:
id: hgnc:9388
label: PRKAR1A
genetic_context:
gene:
preferred_term: PRKAR1A
term:
id: hgnc:9388
label: PRKAR1A
variant_origin: GERMLINE
allelic_hit_role: FIRST_HIT
allelic_events:
- PATHOGENIC_VARIANT
zygosity: HETEROZYGOUS
functional_impact_category: LOSS_OF_FUNCTION
description: >-
Constitutional heterozygous inactivating PRKAR1A variant; a recurrent
coding-region variant was shared by three unrelated kindreds and one
sporadic case.
evidence:
- reference: PMID:10973256
reference_title: Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We subsequently identified three unrelated kindreds with an identical
mutation in the coding region of PRKAR1A.
explanation: >-
Identifies the recurrent germline PRKAR1A lesion in Carney complex
families.
- reference: PMID:10973256
reference_title: Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We conclude that germline mutations in PRKAR1A, an apparent
tumour-suppressor gene, are responsible for the CNC phenotype in a subset
of patients with this disease.
explanation: >-
Establishes PRKAR1A as a tumor suppressor and the cause of the syndrome in
a subset of patients, which places this disorder in the two-hit class.
Note the authors' own qualifiers ("apparent", "a subset") are preserved.
downstream:
- target: Somatic PRKAR1A Second-Hit Loss of Heterozygosity
description: >-
A somatic event removing the retained wild-type allele completes RIalpha
loss in the tumor-forming cell.
- name: Somatic PRKAR1A Second-Hit Loss of Heterozygosity
conforms_to: "germline_two_hit_tumor_predisposition#Somatic Second-Hit Inactivation of the Wild-Type Allele"
description: >-
Tumors from 17q-linked Carney complex families show loss of heterozygosity in
the vicinity of PRKAR1A, including at a polymorphic site in its 5' region.
Detecting that loss is what localized the gene, and it is the direct evidence
that the syndrome follows the classical two-hit architecture rather than
acting through haploinsufficiency alone.
role: amplifier
biological_scale: MOLECULAR
genetic_context:
gene:
preferred_term: PRKAR1A
term:
id: hgnc:9388
label: PRKAR1A
variant_origin: SOMATIC
allelic_hit_role: SECOND_HIT
allelic_events:
- LOSS_OF_HETEROZYGOSITY
functional_impact_category: LOSS_OF_FUNCTION
description: >-
Acquired loss of heterozygosity at the PRKAR1A locus in Carney complex
tumor tissue.
evidence:
- reference: PMID:10973256
reference_title: Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In CNC families mapping to 17q, we detected loss of heterozygosity (LOH)
in the vicinity of the gene (PRKAR1A) encoding protein kinase A regulatory
subunit 1-alpha (RIalpha), including a polymorphic site within its 5'
region.
explanation: >-
The direct demonstration of somatic loss of heterozygosity at the locus,
which is the second hit this node asserts.
downstream:
- target: Loss of RIalpha Restraint on cAMP-Stimulated PKA Signaling
description: >-
With both alleles inactivated, the regulatory subunit no longer restrains
the PKA catalytic subunits in response to cyclic AMP.
- name: Loss of RIalpha Restraint on cAMP-Stimulated PKA Signaling
conforms_to: "germline_two_hit_tumor_predisposition#Biallelic Tumor Suppressor Inactivation in a Susceptible Cell"
description: >-
The rate-limiting state. RIalpha holds the PKA catalytic subunits inactive
until displaced by cyclic AMP; losing it therefore changes the shape of the
response rather than simply raising output. Carney complex tumours show
decreased basal PKA activity but increased cAMP-stimulated activity relative
to non-Carney tumours — an inversion of the normal relationship between
stimulus and kinase output that is the biochemical correlate of the
syndrome's paradoxical endocrine responses.
role: central_effector
biological_scale: MOLECULAR
molecular_functions:
- preferred_term: cAMP-dependent protein kinase regulator activity
term:
id: GO:0008603
label: cAMP-dependent protein kinase regulator activity
modifier: LOSS_OF_FUNCTION
evidence:
- reference: PMID:10973256
reference_title: Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In CNC families mapping to 17q, we detected loss of heterozygosity (LOH)
in the vicinity of the gene (PRKAR1A) encoding protein kinase A regulatory
subunit 1-alpha (RIalpha), including a polymorphic site within its 5'
region.
explanation: >-
Somatic loss of the retained allele in tumor tissue is what makes this a
biallelic state rather than a haploinsufficient one. The PKA-activity
evidence below establishes the functional consequence but not the allelic
state.
- reference: PMID:10973256
reference_title: Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Analysis of PKA activity in CNC tumours demonstrated a decreased basal
activity, but an increase in cAMP-stimulated activity compared with
non-CNC tumours.
explanation: >-
The direct measurement of the altered PKA response in Carney complex
tumours, which is exactly the state this node asserts — and specifically
not a simple increase in basal kinase activity.
downstream:
- target: Multiple Neoplasia and Paradoxical Endocrine Overactivity
description: >-
Unrestrained cAMP-stimulated PKA signalling drives tumor formation and
hormone excess in the affected lineages.
- name: Multiple Neoplasia and Paradoxical Endocrine Overactivity
conforms_to: "germline_two_hit_tumor_predisposition#Early-Onset, Multifocal, and Bilateral Tumor Spectrum"
description: >-
The clinical output: spotty skin pigmentation, cardiac and cutaneous
myxomas, endocrine overactivity — primary pigmented nodular adrenocortical
disease causing ACTH-independent Cushing syndrome, growth-hormone-secreting
pituitary adenoma, thyroid and testicular tumors — and psammomatous melanotic
schwannoma. Lesions are characteristically multiple and recurrent, and
cardiac myxomas may be multichambered and recur after resection, which is why
surveillance continues lifelong rather than ending after successful surgery.
The resemblance to McCune-Albright syndrome, which reaches constitutive cAMP
signalling by a somatic activating GNAS variant instead, is mechanistic
rather than coincidental and was part of the reasoning that identified
PRKAR1A.
role: consequence
biological_scale: ORGANISM
evidence:
- reference: PMID:10973256
reference_title: Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Carney complex (CNC) is a multiple neoplasia syndrome characterized by
spotty skin pigmentation, cardiac and other myxomas, endocrine tumours and
psammomatous melanotic schwannomas.
explanation: >-
Defines the four-component tumor spectrum that this consequence node
asserts.
- reference: PMID:10973256
reference_title: Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Because of its similarities to the McCune-Albright syndrome and other
features, such as paradoxical responses to endocrine signals, genes
implicated in cyclic nucleotide-dependent signalling have been considered
candidates for causing CNC (ref. 10).
explanation: >-
Documents both the paradoxical endocrine responses and the mechanistic
parallel with McCune-Albright syndrome asserted here.
phenotypes:
- category: Cardiovascular
name: Cardiac Myxoma
description: >-
Myxomas may arise in any cardiac chamber, may be multiple, and recur after
resection; they are the principal cause of mortality in Carney complex,
through embolism, obstruction or operative risk.
phenotype_term:
preferred_term: Cardiac myxoma
term:
id: HP:0011672
label: Cardiac myxoma
evidence:
- reference: PMID:10973256
reference_title: Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Carney complex (CNC) is a multiple neoplasia syndrome characterized by
spotty skin pigmentation, cardiac and other myxomas, endocrine tumours and
psammomatous melanotic schwannomas.
explanation: >-
Names cardiac myxoma as a defining component of the syndrome.
- reference: PMID:20301463
reference_title: "Carney Complex."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Cardiac myxomas occur at a young age, may occur in any or all cardiac
chambers, and can manifest as intracardiac obstruction of blood flow,
embolic phenomenon, and/or heart failure.
explanation: >-
GeneReviews Clinical Characteristics section, giving the young onset, the
any-chamber distribution and the three mechanisms of harm — which
together are why echocardiographic surveillance starts in childhood and
never stops.
- category: Dermatologic
name: Multiple Lentigines
description: >-
Spotty skin pigmentation — lentigines with a characteristic distribution
including the vermilion border of the lips, conjunctiva and genital mucosa,
often with blue naevi — which is typically the earliest recognizable feature.
phenotype_term:
preferred_term: Multiple lentigines
term:
id: HP:0001003
label: Multiple lentigines
evidence:
- reference: PMID:10973256
reference_title: Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Carney complex (CNC) is a multiple neoplasia syndrome characterized by
spotty skin pigmentation, cardiac and other myxomas, endocrine tumours and
psammomatous melanotic schwannomas.
explanation: >-
Names spotty skin pigmentation as a defining feature.
- reference: PMID:20301463
reference_title: "Carney Complex."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Pale brown to black lentigines are the most common presenting feature of
CNC and typically increase in number at puberty.
explanation: >-
GeneReviews Clinical Characteristics section, identifying lentigines as
the commonest presenting feature and giving their pubertal timing.
- category: Neurologic
name: Schwannoma
description: >-
Psammomatous melanotic schwannoma, a distinctive nerve sheath tumor that is
near-specific to Carney complex and may be multiple; a minority behave
malignantly.
phenotype_term:
preferred_term: Schwannoma
term:
id: HP:0100008
label: Schwannoma
evidence:
- reference: PMID:10973256
reference_title: Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Carney complex (CNC) is a multiple neoplasia syndrome characterized by
spotty skin pigmentation, cardiac and other myxomas, endocrine tumours and
psammomatous melanotic schwannomas.
explanation: >-
Names psammomatous melanotic schwannoma as a defining component.
- reference: PMID:20301463
reference_title: "Carney Complex."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Psammomatous melanotic schwannoma (PMS), a rare tumor of the nerve sheath,
occurs in an estimated 10% of affected individuals.
explanation: >-
GeneReviews Clinical Characteristics section, quantifying the frequency of
this near-pathognomonic tumor at roughly 10%.
- category: Endocrine
name: Primary Hypercortisolism
description: >-
Primary pigmented nodular adrenocortical disease (PPNAD) causes an
ACTH-independent Cushing syndrome and is the commonest endocrine tumor of
the complex, affecting about a quarter of patients. It is the setting of the
paradoxical dexamethasone response that follows from the altered PKA
dose-response curve curated in this entry's pathophysiology.
phenotype_term:
preferred_term: Primary hypercortisolism
term:
id: HP:0001579
label: Primary hypercortisolism
evidence:
- reference: PMID:20301463
reference_title: "Carney Complex."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Primary pigmented nodular adrenocortical disease (PPNAD), which causes
Cushing syndrome, is the most frequently observed endocrine tumor in CNC,
occurring in approximately 25% of affected individuals.
explanation: >-
GeneReviews Clinical Characteristics section, naming the lesion, its
endocrine consequence and its frequency.
- category: Endocrine
name: Thyroid Nodule
description: >-
Multiple thyroid nodules occur in up to three quarters of patients and are
mostly nonfunctioning follicular adenomas, which is why annual thyroid
ultrasound is part of surveillance.
phenotype_term:
preferred_term: Thyroid nodule
term:
id: HP:0025388
label: Thyroid nodule
evidence:
- reference: PMID:20301463
reference_title: "Carney Complex."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Up to 75% of individuals with CNC have multiple thyroid nodules, most of
which are nonfunctioning thyroid follicular adenomas.
explanation: >-
GeneReviews Clinical Characteristics section, quantifying frequency and
establishing that most nodules are benign and nonfunctioning.
- category: Reproductive
name: Large Cell Calcifying Sertoli Cell Tumor
description: >-
A characteristic testicular tumor of the complex, present in a third of
affected boys in the first decade and in most adult males. Its endocrine
activity is what makes it clinically urgent in childhood — it can drive
gynaecomastia and premature epiphyseal fusion.
phenotype_term:
preferred_term: Sertoli cell neoplasm
term:
id: HP:0100619
label: Sertoli cell neoplasm
evidence:
- reference: PMID:20301463
reference_title: "Carney Complex."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Large cell calcifying Sertoli cell tumors (LCCSCTs) are observed in one
third of affected males within the first decade and in most adult males.
explanation: >-
GeneReviews Clinical Characteristics section, giving the frequency in both
childhood and adulthood and the basis for annual testicular ultrasound
from childhood in males.
genetic:
- name: PRKAR1A
gene_term:
preferred_term: PRKAR1A
term:
id: hgnc:9388
label: PRKAR1A
relationship_type: CAUSATIVE
notes: >-
PRKAR1A at 17q22-24 encodes the PKA type I-alpha regulatory subunit RIalpha.
Germline inactivating variants cause Carney complex in a subset of patients;
tumors additionally show loss of heterozygosity at the locus. A second,
separately mapped locus at 2p16 accounts for the remaining families.
evidence:
- reference: PMID:10973256
reference_title: Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Analysis of additional cases revealed the same mutation in a sporadic case
of CNC, and different mutations in three other families, including one
with isolated inherited cardiac myxomas.
explanation: >-
Documents the allelic spectrum, including a de novo sporadic case and a
family with an isolated cardiac-myxoma phenotype, which supports the
variable expressivity curated in this entry.
references:
- reference: PMID:20301463
title: "Carney Complex."
tags:
- GeneReviews
treatments:
- name: Lifelong Echocardiographic Surveillance for Cardiac Myxoma
notes: >-
Curated under `treatments:` as a management intervention, not as a claim
that imaging or biochemistry is itself therapeutic. In a two-hit
predisposition syndrome the second hit cannot be prevented, so the only
available lever is stage at detection: surveillance is the intervention
that converts an unavoidable tumor into a resectable one. Where a
`target_mechanisms` link is present it points at the clinical-outcome node
for that reason, and never at an upstream mechanistic node.
description: >-
The single most consequential intervention in Carney complex. Because
myxomas arise at a young age, in any chamber, and recur after excision,
echocardiography begins in childhood and moves to twice-yearly in anyone
who has already had one excised. Surveillance does not end after a
successful operation — recurrence in retained tissue is expected, which is
the clinical expression of independent second hits.
therapeutic_modality: DEVICE
treatment_term:
preferred_term: Echocardiography Test
term:
id: NCIT:C16525
label: Echocardiography Test
target_mechanisms:
- target: Multiple Neoplasia and Paradoxical Endocrine Overactivity
treatment_effect: INHIBITS
description: >-
Surveillance acts on the consequence node by detecting myxomas before
they obstruct, embolise or cause heart failure; it does not prevent their
formation.
evidence:
- reference: PMID:20301463
reference_title: "Carney Complex."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Echocardiography annually beginning in childhood, biannually for those
with a history of excised myxoma
explanation: >-
GeneReviews Management section, giving the surveillance interval and its
escalation after a first myxoma — the schedule this entry curates as
lifelong.
- name: Surgical Excision of Myxomas and Endocrine Tumors
description: >-
Cardiac myxomas are removed by open heart surgery; cutaneous and mammary
myxomas are excised locally. Endocrine disease is managed organ by organ,
including bilateral adrenalectomy for the Cushing syndrome of PPNAD. In boys
with aggressive Sertoli cell tumors, orchiectomy is done specifically to
prevent premature epiphyseal fusion and central precocious puberty rather
than for malignant potential.
therapeutic_modality: SURGERY
treatment_term:
preferred_term: Surgical Procedure
term:
id: NCIT:C15329
label: Surgical Procedure
target_mechanisms:
- target: Multiple Neoplasia and Paradoxical Endocrine Overactivity
treatment_effect: INHIBITS
description: >-
Resection removes established lesions and their hormonal output; the
germline lesion and the risk of further tumors are unchanged.
evidence:
- reference: PMID:20301463
reference_title: "Carney Complex."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Surgical excision via open heart surgery for cardiac myxomas; surgical
excision of cutaneous and mammary myxomas; bilateral adrenalectomy for
Cushing syndrome; transsphenoidal surgery for pituitary adenoma
explanation: >-
GeneReviews Management section, giving the organ-by-organ surgical
approach across the complex.
- reference: PMID:20301463
reference_title: "Carney Complex."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
orchiectomy for boys with aggressive LCCSCT and gynecomastia to avoid
premature epiphyseal fusion and induction of central precocious puberty
explanation: >-
GeneReviews Management section. The stated indication is endocrine
consequence rather than malignancy, which is why this is a growth-related
decision in childhood.
- name: Endocrine Surveillance from Adolescence
description: >-
Biochemical surveillance across the endocrine axes the complex affects —
cortisol, IGF-1, thyroid and gonadal — beginning in adolescence, with
growth rate and pubertal staging monitored at every visit in children.
therapeutic_modality: OTHER
treatment_term:
preferred_term: Supportive Care
term:
id: NCIT:C15747
label: Supportive Care
target_mechanisms:
- target: Multiple Neoplasia and Paradoxical Endocrine Overactivity
treatment_effect: INHIBITS
description: >-
Detects hormonal overactivity before it produces irreversible endocrine
consequences; acts on the consequence node, not on the lesion.
evidence:
- reference: PMID:20301463
reference_title: "Carney Complex."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
urinary free cortisol levels annually beginning in adolescence with
diurnal cortisol levels, dexamethasome stimulation test, and adrenal CT as
needed; annual serum IGF-1 beginning in adolescence
explanation: >-
GeneReviews Management section, giving the adrenal and somatotroph
surveillance analytes and their start age.
- reference: PMID:20301463
reference_title: "Carney Complex."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
monitor growth rate and pubertal staging at each visit and testicular
ultrasound annually in males beginning in childhood
explanation: >-
GeneReviews Management section, giving the paediatric surveillance that
exists because the Sertoli cell tumor acts on growth and puberty.
diagnosis:
- name: Clinical Diagnostic Criteria for Carney Complex
description: >-
A clinical diagnosis rests on two or more major diagnostic criteria drawn
from the pigmentary, myxomatous, endocrine and schwannoma features. The
median age at diagnosis is 20 years, so most patients are identified in
adolescence or early adulthood.
diagnosis_term:
preferred_term: Clinical Evaluation
term:
id: NCIT:C124351
label: Clinical Evaluation
results: >-
Two or more major criteria establish the clinical diagnosis and prompt
confirmatory PRKAR1A testing.
evidence:
- reference: PMID:20301463
reference_title: "Carney Complex."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The clinical diagnosis of CNC is established in a proband with two or more
major diagnostic criteria.
explanation: >-
GeneReviews Diagnosis/Testing section, giving the clinical diagnostic
threshold.
- reference: PMID:20301463
reference_title: "Carney Complex."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The median age of diagnosis is 20 years.
explanation: >-
GeneReviews Clinical Characteristics section, giving the age at which the
diagnosis is typically made — the practical target that surveillance of
at-risk relatives aims to beat.
- name: Molecular Genetic Testing for PRKAR1A
description: >-
A heterozygous germline PRKAR1A pathogenic variant establishes the molecular
diagnosis. Where testing is uninformative — expected in the subset of
families mapping to the second locus at 2p16 — GeneReviews recommends
surveillance of at-risk relatives on the basis of their 50% prior risk
rather than discharging them.
diagnosis_term:
preferred_term: Genetic Testing
term:
id: NCIT:C15709
label: Genetic Testing
results: >-
A heterozygous germline pathogenic PRKAR1A variant confirms the diagnosis;
an uninformative result does not exclude it.
evidence:
- reference: PMID:20301463
reference_title: "Carney Complex."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The molecular diagnosis can be established in a proband with suggestive
findings and a heterozygous germline pathogenic variant in PRKAR1A
identified by molecular genetic testing.
explanation: >-
GeneReviews Diagnosis/Testing section, stating the confirmatory molecular
test.
- reference: PMID:20301463
reference_title: "Carney Complex."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Surveillance is recommended for individuals at 50% risk when molecular
genetic testing is not possible or is not informative.
explanation: >-
GeneReviews Evaluation of Relatives at Risk. This is the clinically
important corollary of the syndrome's locus heterogeneity: a negative or
unavailable PRKAR1A result does not release an at-risk relative from
surveillance.
clinical_trials:
- name: NCT00668291
phase: NOT_APPLICABLE
status: COMPLETED
description: >-
Completed French cohort study assessing the clinical, genetic, biological
and imaging course of Carney complex and primary pigmented nodular
adrenocortical disease, with PRKAR1A genotyping in an isolated-myxoma
comparison cohort.
target_phenotypes:
- preferred_term: Primary pigmented nodular adrenocortical disease
term:
id: HP:0001579
label: Primary hypercortisolism
- preferred_term: Cardiac myxoma
term:
id: HP:0011672
label: Cardiac myxoma
evidence:
- reference: clinicaltrials:NCT00668291
reference_title: Assessment of the Clinical Symptoms of the Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and the CARNEY Complex (CNC).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Cohort CNC-PPNAD will be investigated with clinical, genetic, biological and imaging work-up every year during 3 years.
explanation: >-
Registry record for the completed prospective CNC/PPNAD natural-history
cohort with annual multimodal assessment.