PPNAD4
MCID: PGM022
MIFTS: 26

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 58 30 6 74
Chromosome 19p13 Duplication Syndrome 58 76
Ppnad4 58 76
Adrenocortical Disease, Nodular, Pigmented, Primary, Type 4 41
Primary Pigmented Nodular Adrenocortical Disease 4 76
Cushing Syndrome, Adrenal, Due to Ppnad4 58
Adrenal Cushing Syndrome Due to Ppnad4 76

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant

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


HPO:

33
pigmented nodular adrenocortical disease, primary, 4:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Pigmented Nodular Adrenocortical Disease, Primary, 4

UniProtKB/Swiss-Prot : 76 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 : 58 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:

33 (show all 17)
# Description HPO Frequency HPO Source Accession
1 emotional lability 33 HP:0000712
2 depressivity 33 HP:0000716
3 diabetes mellitus 33 HP:0000819
4 hypertension 33 HP:0000822
5 osteopenia 33 HP:0000938
6 osteoporosis 33 HP:0000939
7 acne 33 HP:0001061
8 alopecia 33 HP:0001596
9 bruising susceptibility 33 HP:0000978
10 increased body weight 33 HP:0004324
11 proximal muscle weakness 33 HP:0003701
12 adrenal hyperplasia 33 HP:0008221
13 hirsutism 33 HP:0001007
14 fragile skin 33 HP:0001030
15 moon facies 33 HP:0500011
16 primary hypercortisolism 33 HP:0001579
17 dorsocervical fat pad 33 HP:0025383

Symptoms via clinical synopsis from OMIM:

58
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

Growth Weight:
weight gain

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

Skeletal:
osteopenia
osteoporosis

Skin Nails Hair Hair:
alopecia
hirsutism

Laboratory Abnormalities:
increased serum cortisol

Head And Neck Face:
moon facies

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 30 PRKACA

Anatomical Context for Pigmented Nodular Adrenocortical Disease, Primary, 4

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

42
Adrenal Gland, Cortex, Skin, Bone

Publications for Pigmented Nodular Adrenocortical Disease, Primary, 4

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

# Title Authors Year
1
Constitutive activation of PKA catalytic subunit in adrenal Cushing's syndrome. ( 24571724 )
2014
2
Activating hotspot L205R mutation in PRKACA and adrenal Cushing's syndrome. ( 24700472 )
2014
3
Recurrent somatic mutations underlie corticotropin-independent Cushing's syndrome. ( 24855271 )
2014
4
Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors. ( 24747643 )
2014

Variations for Pigmented Nodular Adrenocortical Disease, Primary, 4

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

76
# Symbol AA change Variation ID SNP ID
1 PRKACA p.Leu206Arg VAR_071707 rs386352352

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

6
# Gene Variation Type Significance SNP ID Assembly Location
1 PRKACA NM_002730.3(PRKACA): c.617T> G (p.Leu206Arg) single nucleotide variant Pathogenic/Likely pathogenic rs386352352 GRCh37 Chromosome 19, 14208416: 14208416
2 PRKACA NM_002730.3(PRKACA): c.617T> G (p.Leu206Arg) single nucleotide variant Pathogenic/Likely pathogenic rs386352352 GRCh38 Chromosome 19, 14097604: 14097604
3 PRKACA NM_002730.3(PRKACA): c.597_599dup (p.Leu199_Cys200insTrp) duplication Pathogenic rs724160013 GRCh38 Chromosome 19, 14097622: 14097624
4 PRKACA NM_002730.3(PRKACA): c.597_599dup (p.Leu199_Cys200insTrp) duplication Pathogenic rs724160013 GRCh37 Chromosome 19, 14208434: 14208436

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

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75 UMLS via Orphanet
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