PPNAD4
MCID: PGM022
MIFTS: 25

Pigmented Nodular Adrenocortical Disease, Primary, 4 (PPNAD4)

Categories: Bone diseases, Endocrine diseases, Genetic diseases, Metabolic diseases, Rare diseases, Reproductive diseases
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Aliases & Classifications for Pigmented Nodular Adrenocortical Disease, Primary, 4

MalaCards integrated aliases for Pigmented Nodular Adrenocortical Disease, Primary, 4:

Name: Pigmented Nodular Adrenocortical Disease, Primary, 4 57 28 5 71
Chromosome 19p13 Duplication Syndrome 57 73
Ppnad4 57 73
Adrenocortical Disease, Nodular, Pigmented, Primary, Type 4 38
Primary Pigmented Nodular Adrenocortical Disease 4 73
Cushing Syndrome, Adrenal, Due to Ppnad4 57
Adrenal Cushing Syndrome Due to Ppnad4 73

Characteristics:


Inheritance:

Autosomal dominant 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
variable age at onset
somatic mutations occur in adrenal tumor tissue


Classifications:



Summaries for Pigmented Nodular Adrenocortical Disease, Primary, 4

UniProtKB/Swiss-Prot: 73 A rare bilateral adrenal defect causing ACTH-independent Cushing syndrome. Macroscopic appearance of the adrenals is characteristic with small pigmented micronodules observed in the cortex. Adrenal glands show overall normal size and weight, and multiple small yellow- to-dark brown nodules surrounded by a cortex with a uniform appearance. Microscopically, there are moderate diffuse cortical hyperplasia with mostly nonpigmented nodules, multiple capsular deficits and massive circumscribed and infiltrating extra-adrenal cortical excrescences with micronodules. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes.

MalaCards based summary: Pigmented Nodular Adrenocortical Disease, Primary, 4, is also known as chromosome 19p13 duplication syndrome, and has symptoms including cushingoid facies An important gene associated with Pigmented Nodular Adrenocortical Disease, Primary, 4 is PRKACA (Protein Kinase CAMP-Activated Catalytic Subunit Alpha). Affiliated tissues include cortex, skin and heart, and related phenotypes are emotional lability and depression

OMIM®: 57 Cushing syndrome is a clinical designation for the systemic signs and symptoms arising from excess cortisol production. Affected individuals typically show hypertension, impaired glucose tolerance, central obesity, osteoporosis, and sometimes depression. Corticotropin-independent Cushing syndrome results from autonomous cortisol production by the adrenal glands, often associated with adrenocortical tumors. Adrenocortical tumors are most common in adult females (summary by Cao et al., 2014; Sato et al., 2014). (615830) (Updated 08-Dec-2022)

Related Diseases for Pigmented Nodular Adrenocortical Disease, Primary, 4

Symptoms & Phenotypes for Pigmented Nodular Adrenocortical Disease, Primary, 4

Human phenotypes related to Pigmented Nodular Adrenocortical Disease, Primary, 4:

30 (show all 17)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 emotional lability 30 HP:0000712
2 depression 30 HP:0000716
3 diabetes mellitus 30 HP:0000819
4 hypertension 30 HP:0000822
5 osteopenia 30 HP:0000938
6 acne 30 HP:0001061
7 osteoporosis 30 HP:0000939
8 alopecia 30 HP:0001596
9 bruising susceptibility 30 HP:0000978
10 hirsutism 30 HP:0001007
11 proximal muscle weakness 30 HP:0003701
12 adrenal hyperplasia 30 HP:0008221
13 fragile skin 30 HP:0001030
14 increased body weight 30 HP:0004324
15 dorsocervical fat pad 30 HP:0025383
16 moon facies 30 HP:0500011
17 primary hypercortisolism 30 HP:0001579

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Neurologic Behavioral Psychiatric Manifestations:
emotional lability
depression

Cardiovascular Vascular:
hypertension

Skin Nails Hair Skin:
acne
easy bruising
skin fragility
stria

Muscle Soft Tissue:
proximal muscle weakness
buffalo hump

Laboratory Abnormalities:
increased serum cortisol

Endocrine Features:
diabetes mellitus
cushing syndrome
acth-independent hypercortisolemia
adrenal hyperplasia, bilateral
adrenal adenomas, bilateral

Skeletal:
osteopenia
osteoporosis

Skin Nails Hair Hair:
alopecia
hirsutism

Head And Neck Face:
moon facies

Growth Weight:
weight gain

Clinical features from OMIM®:

615830 (Updated 08-Dec-2022)

UMLS symptoms related to Pigmented Nodular Adrenocortical Disease, Primary, 4:


cushingoid facies

Drugs & Therapeutics for Pigmented Nodular Adrenocortical Disease, Primary, 4

Search Clinical Trials, NIH Clinical Center for Pigmented Nodular Adrenocortical Disease, Primary, 4

Genetic Tests for Pigmented Nodular Adrenocortical Disease, Primary, 4

Genetic tests related to Pigmented Nodular Adrenocortical Disease, Primary, 4:

# Genetic test Affiliating Genes
1 Pigmented Nodular Adrenocortical Disease, Primary, 4 28 PRKACA

Anatomical Context for Pigmented Nodular Adrenocortical Disease, Primary, 4

Organs/tissues related to Pigmented Nodular Adrenocortical Disease, Primary, 4:

MalaCards : Cortex, Skin, Heart

Publications for Pigmented Nodular Adrenocortical Disease, Primary, 4

Articles related to Pigmented Nodular Adrenocortical Disease, Primary, 4:

# Title Authors PMID Year
1
Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors. 57 5
24747643 2014
2
Activating hotspot L205R mutation in PRKACA and adrenal Cushing's syndrome. 57 5
24700472 2014
3
Recurrent somatic mutations underlie corticotropin-independent Cushing's syndrome. 57 5
24855271 2014
4
Constitutive activation of PKA catalytic subunit in adrenal Cushing's syndrome. 57 5
24571724 2014
5
Germline PRKACA amplification causes variable phenotypes that may depend on the extent of the genomic defect: molecular mechanisms and clinical presentations. 57
25924874 2015
6
Differential expression of genes participating in cardiomyocyte electrophysiological remodeling via membrane ionic mechanisms and Ca2+-handling in human heart failure. 62
31520233 2020

Variations for Pigmented Nodular Adrenocortical Disease, Primary, 4

ClinVar genetic disease variations for Pigmented Nodular Adrenocortical Disease, Primary, 4:

5
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PRKACA NM_002730.3(PRKACA):c.617T>G (p.Leu206Arg) SNV Pathogenic
91945 rs386352352 GRCh37: 19:14208416-14208416
GRCh38: 19:14097604-14097604
2 PRKACA NM_002730.4(PRKACA):c.597_599dup (p.Leu199_Cys200insTrp) DUP Pathogenic
162471 rs724160013 GRCh37: 19:14208434-14208436
GRCh38: 19:14097621-14097622

UniProtKB/Swiss-Prot genetic disease variations for Pigmented Nodular Adrenocortical Disease, Primary, 4:

73
# Symbol AA change Variation ID SNP ID
1 PRKACA p.Leu206Arg VAR_071707 rs386352352

Expression for Pigmented Nodular Adrenocortical Disease, Primary, 4

Search GEO for disease gene expression data for Pigmented Nodular Adrenocortical Disease, Primary, 4.

Pathways for Pigmented Nodular Adrenocortical Disease, Primary, 4

GO Terms for Pigmented Nodular Adrenocortical Disease, Primary, 4

Sources for Pigmented Nodular Adrenocortical Disease, Primary, 4

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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