PPNAD4
MCID: PGM022
MIFTS: 23

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 57 29 6 72
Chromosome 19p13 Duplication Syndrome 57 74
Ppnad4 57 74
Adrenocortical Disease, Nodular, Pigmented, Primary, Type 4 40
Primary Pigmented Nodular Adrenocortical Disease 4 74
Cushing Syndrome, Adrenal, Due to Ppnad4 57
Adrenal Cushing Syndrome Due to Ppnad4 74

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

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


HPO:

32
pigmented nodular adrenocortical disease, primary, 4:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

MeSH 44 D003480
UMLS 72 C4014425

Summaries for Pigmented Nodular Adrenocortical Disease, Primary, 4

UniProtKB/Swiss-Prot : 74 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 emotional lability and depressivity

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)

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:

32 (show all 17)
# Description HPO Frequency HPO Source Accession
1 emotional lability 32 HP:0000712
2 depressivity 32 HP:0000716
3 diabetes mellitus 32 HP:0000819
4 hypertension 32 HP:0000822
5 osteopenia 32 HP:0000938
6 osteoporosis 32 HP:0000939
7 acne 32 HP:0001061
8 alopecia 32 HP:0001596
9 bruising susceptibility 32 HP:0000978
10 increased body weight 32 HP:0004324
11 proximal muscle weakness 32 HP:0003701
12 adrenal hyperplasia 32 HP:0008221
13 hirsutism 32 HP:0001007
14 fragile skin 32 HP:0001030
15 primary hypercortisolism 32 HP:0001579
16 dorsocervical fat pad 32 HP:0025383
17 moon facies 32 HP:0500011

Symptoms via clinical synopsis from OMIM:

57
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

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:

41
Adrenal Gland, Cortex, Skin

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. 8 71
24747643 2014
2
Recurrent somatic mutations underlie corticotropin-independent Cushing's syndrome. 8 71
24855271 2014
3
Activating hotspot L205R mutation in PRKACA and adrenal Cushing's syndrome. 8 71
24700472 2014
4
Constitutive activation of PKA catalytic subunit in adrenal Cushing's syndrome. 8 71
24571724 2014

Variations for Pigmented Nodular Adrenocortical Disease, Primary, 4

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

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 PRKACA NM_002730.4(PRKACA): c.597_599dup (p.Cys200_Gly201insTrp) duplication Pathogenic rs724160013 19:14208434-14208436 19:14097622-14097624
2 PRKACA NM_002730.3(PRKACA): c.617T> G (p.Leu206Arg) single nucleotide variant Pathogenic/Likely pathogenic rs386352352 19:14208416-14208416 19:14097604-14097604

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

74
# 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
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10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
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28 GO
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30 HGMD
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32 HPO
33 ICD10
34 ICD10 via Orphanet
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36 IUPHAR
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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