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

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 56 29 6 71
Chromosome 19p13 Duplication Syndrome 56 73
Ppnad4 56 73
Adrenocortical Disease, Nodular, Pigmented, Primary, Type 4 39
Primary Pigmented Nodular Adrenocortical Disease 4 73
Cushing Syndrome, Adrenal, Due to Ppnad4 56
Adrenal Cushing Syndrome Due to Ppnad4 73

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
variable age at onset
somatic mutations occur in adrenal tumor tissue


HPO:

31
pigmented nodular adrenocortical disease, primary, 4:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Pigmented Nodular Adrenocortical Disease, Primary, 4

UniProtKB/Swiss-Prot : 73 Primary pigmented nodular adrenocortical disease 4: 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 adrenal gland, cortex and skin, and related phenotypes are acne and osteopenia

OMIM : 56 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)

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:

31 (show all 17)
# Description HPO Frequency HPO Source Accession
1 acne 31 HP:0001061
2 osteopenia 31 HP:0000938
3 osteoporosis 31 HP:0000939
4 hypertension 31 HP:0000822
5 depressivity 31 HP:0000716
6 alopecia 31 HP:0001596
7 diabetes mellitus 31 HP:0000819
8 bruising susceptibility 31 HP:0000978
9 emotional lability 31 HP:0000712
10 hirsutism 31 HP:0001007
11 proximal muscle weakness 31 HP:0003701
12 adrenal hyperplasia 31 HP:0008221
13 fragile skin 31 HP:0001030
14 increased body weight 31 HP:0004324
15 primary hypercortisolism 31 HP:0001579
16 dorsocervical fat pad 31 HP:0025383
17 moon facies 31 HP:0500011

Symptoms via clinical synopsis from OMIM:

56
Skin Nails Hair Skin:
acne
easy bruising
skin fragility
stria

Cardiovascular Vascular:
hypertension

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

Muscle Soft Tissue:
proximal muscle weakness
buffalo hump

Laboratory Abnormalities:
increased serum cortisol

Skeletal:
osteopenia
osteoporosis

Skin Nails Hair Hair:
alopecia
hirsutism

Neurologic Behavioral Psychiatric Manifestations:
emotional lability
depression

Head And Neck Face:
moon facies

Growth Weight:
weight gain

Clinical features from OMIM:

615830

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 29 PRKACA

Anatomical Context for Pigmented Nodular Adrenocortical Disease, Primary, 4

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

40
Adrenal Gland, 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. 56 6
24747643 2014
2
Activating hotspot L205R mutation in PRKACA and adrenal Cushing's syndrome. 6 56
24700472 2014
3
Recurrent somatic mutations underlie corticotropin-independent Cushing's syndrome. 6 56
24855271 2014
4
Constitutive activation of PKA catalytic subunit in adrenal Cushing's syndrome. 6 56
24571724 2014
5
Differential expression of genes participating in cardiomyocyte electrophysiological remodeling via membrane ionic mechanisms and Ca2+-handling in human heart failure. 61
31520233 2020

Variations for Pigmented Nodular Adrenocortical Disease, Primary, 4

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

6 ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PRKACA NM_002730.4(PRKACA):c.597_599dup (p.Cys200_Gly201insTrp)duplication Pathogenic 162471 rs724160013 19:14208434-14208436 19:14097621-14097622
2 PRKACA NM_002730.3(PRKACA):c.617T>G (p.Leu206Arg)SNV Pathogenic/Likely pathogenic 91945 rs386352352 19:14208416-14208416 19:14097604-14097604

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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