CGL4
MCID: LPD035
MIFTS: 51

Lipodystrophy, Congenital Generalized, Type 4 (CGL4)

Categories: Endocrine diseases, Genetic diseases, Muscle diseases, Rare diseases, Skin diseases

Aliases & Classifications for Lipodystrophy, Congenital Generalized, Type 4

MalaCards integrated aliases for Lipodystrophy, Congenital Generalized, Type 4:

Name: Lipodystrophy, Congenital Generalized, Type 4 57 53 29 13 6 40 73
Cgl4 57 12 53 75
Congenital Generalized Lipodystrophy Type 4 12 53 15
Lipodystrophy, Berardinelli-Seip Congenital, Type 4, with Muscular Dystrophy 57 53
Berardinelli-Seip Congenital Lipodystrophy, Type 4, with Muscular Dystrophy 57 53
Berardinelli-Seip Congenital Lipodystrophy Type 4 with Muscular Dystrophy 12 75
Generalized Congenital Lipodystrophy with Myopathy 12 53
Gcl4 12 53
Berardinelli-Seip Congenital Lipodystrophy Type 4 75
Generalized Congenital Lipodystrophy Type 4 12
Congenital Generalized Lipodystrophy 4 75
Brunzell Syndrome Agpat2-Related 12
Bscl4 12

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy or early childhood
sudden death due to cardiac arrhythmia may occur


HPO:

32
lipodystrophy, congenital generalized, type 4:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Lipodystrophy, Congenital Generalized, Type 4

UniProtKB/Swiss-Prot : 75 Congenital generalized lipodystrophy 4: A disorder characterized by the association of congenital generalized lipodystrophy with muscular dystrophy and cardiac anomalies. Congenital generalized lipodystrophy is characterized by a near complete absence of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes.

MalaCards based summary : Lipodystrophy, Congenital Generalized, Type 4, also known as cgl4, is related to lipodystrophy, congenital generalized, type 1 and congenital generalized lipodystrophy, and has symptoms including constipation, generalized muscle weakness and myalgia. An important gene associated with Lipodystrophy, Congenital Generalized, Type 4 is CAVIN1 (Caveolae Associated Protein 1), and among its related pathways/superpathways are Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) and Glucose / Energy Metabolism. Affiliated tissues include liver, skin and smooth muscle, and related phenotypes are osteopenia and failure to thrive

Disease Ontology : 12 A congenital generalized lipodystrophy that has material basis in an autosomal recessive mutation of PTRF on chromosome 17q21.2.

OMIM : 57 Congenital generalized lipodystrophy type 4 combines the phenotype of classic Berardinelli-Seip lipodystrophy (608594) with muscular dystrophy and cardiac conduction anomalies (Hayashi et al., 2009). For a general description and a discussion of genetic heterogeneity of congenital generalized lipodystrophy, see CGL1 (608594). (613327)

Related Diseases for Lipodystrophy, Congenital Generalized, Type 4

Diseases in the Acquired Generalized Lipodystrophy family:

Lipodystrophy, Congenital Generalized, Type 2 Lipodystrophy, Congenital Generalized, Type 1
Lipodystrophy, Congenital Generalized, Type 3 Lipodystrophy, Congenital Generalized, Type 4
Congenital Generalized Lipodystrophy

Diseases related to Lipodystrophy, Congenital Generalized, Type 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 23)
# Related Disease Score Top Affiliating Genes
1 lipodystrophy, congenital generalized, type 1 32.3 ADIPOQ AGPAT2 BSCL2 LMNA
2 congenital generalized lipodystrophy 30.2 AGPAT2 BSCL2 CAV1 CAVIN1 LMNA
3 mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome 29.9 ADIPOQ AGPAT2 BSCL2 LMNA
4 eosinophilic variant of chromophobe renal cell carcinoma 10.1 CAV1 SLC2A1
5 berardinelli-seip congenital lipodystrophy 10.1 AGPAT2 BSCL2 CAV1
6 spastic paraplegia 17, autosomal dominant 10.1 AGPAT2 BSCL2
7 lipodystrophy, familial partial, type 3 10.1 AGPAT2 BSCL2 LMNA
8 autosomal dominant limb-girdle muscular dystrophy type 1b 10.1 CAV3 LMNA
9 autosomal dominant limb-girdle muscular dystrophy 10.0 CAV1 CAV3 LMNA
10 cardiac arrhythmia 10.0
11 long qt syndrome 10.0
12 myopathy 10.0
13 muscular dystrophy 10.0
14 lipodystrophy, congenital generalized, type 2 10.0 AGPAT2 BSCL2 CAVIN1 LMNA
15 familial partial lipodystrophy 10.0 AGPAT2 BSCL2 CAVIN1 LMNA
16 lipodystrophy, familial partial, type 2 10.0 AGPAT2 LMNA
17 complete generalized lipodystrophy 9.9 AGPAT2 BSCL2 CAV1 CAVIN1 LMNA
18 early onset absence epilepsy 9.8 SLC2A1 SLC2A14 SLC2A3
19 xanthogranulomatous cholecystitis 9.8 SLC2A1 SLC2A14 SLC2A3
20 diabetes mellitus, noninsulin-dependent 9.6 ADIPOQ LMNA SCD SLC2A1 SLC2A3
21 acquired generalized lipodystrophy 9.6 ADIPOQ AGL AGPAT2 BSCL2 CAV1 CAVIN1
22 body mass index quantitative trait locus 11 9.6 ADIPOQ CEBPA LMNA SCD SLC2A1
23 lipodystrophy, congenital generalized, type 3 9.6 AGPAT2 BSCL2 CAV1 CAVIN1 CEBPA SCD

Graphical network of the top 20 diseases related to Lipodystrophy, Congenital Generalized, Type 4:



Diseases related to Lipodystrophy, Congenital Generalized, Type 4

Symptoms & Phenotypes for Lipodystrophy, Congenital Generalized, Type 4

Symptoms via clinical synopsis from OMIM:

57
Skeletal:
osteopenia
osteoporosis
joint contractures

Abdomen Gastrointestinal:
dysphagia
constipation
ileus
poor feeding
esophageal dilatation
more
Abdomen Spleen:
splenomegaly

Cardiovascular Heart:
arrhythmia
tachycardia
atrial fibrillation
bradycardia
long qt syndrome

Endocrine Features:
hyperinsulinemia
insulin resistance
acromegaloid features
decreased growth hormone secretion (1 patient)

Immunology:
recurrent infections
defective humoral immunity
transient iga deficiency (1 patient)

Abdomen External Features:
protruding abdomen
prominent umbilicus

Growth Other:
failure to thrive

Skeletal Spine:
scoliosis
hyperlordosis
spinal rigidity
atlanto-axial instability

Abdomen Liver:
hepatomegaly
fatty liver

Skin Nails Hair Hair:
acanthosis nigricans
hirsutism (less common)

Muscle Soft Tissue:
myalgia
muscle stiffness
exercise intolerance
muscle weakness, proximal
muscle hypertrophy
more
Laboratory Abnormalities:
increased serum creatine kinase
increased serum triglycerides
abnormal liver enzymes


Clinical features from OMIM:

613327

Human phenotypes related to Lipodystrophy, Congenital Generalized, Type 4:

32 (show all 39)
# Description HPO Frequency HPO Source Accession
1 osteopenia 32 HP:0000938
2 failure to thrive 32 HP:0001508
3 dysphagia 32 HP:0002015
4 constipation 32 HP:0002019
5 scoliosis 32 HP:0002650
6 hyperlordosis 32 HP:0003307
7 splenomegaly 32 HP:0001744
8 hepatomegaly 32 HP:0002240
9 flexion contracture 32 HP:0001371
10 osteoporosis 32 HP:0000939
11 elevated serum creatine phosphokinase 32 HP:0003236
12 generalized muscle weakness 32 HP:0003324
13 hypertriglyceridemia 32 HP:0002155
14 acanthosis nigricans 32 HP:0000956
15 feeding difficulties 32 HP:0011968
16 hepatic steatosis 32 HP:0001397
17 hyperinsulinemia 32 HP:0000842
18 prolonged qt interval 32 HP:0001657
19 spinal rigidity 32 HP:0003306
20 lipodystrophy 32 HP:0009125
21 myalgia 32 HP:0003326
22 muscle stiffness 32 HP:0003552
23 ileus 32 HP:0002595
24 recurrent infections 32 HP:0002719
25 pyloric stenosis 32 HP:0002021
26 proximal muscle weakness 32 HP:0003701
27 skeletal muscle hypertrophy 32 HP:0003712
28 muscular dystrophy 32 HP:0003560
29 exercise intolerance 32 HP:0003546
30 iga deficiency 32 HP:0002720
31 tachycardia 32 HP:0001649
32 atrial fibrillation 32 HP:0005110
33 insulin resistance 32 HP:0000855
34 hirsutism 32 occasional (7.5%) HP:0001007
35 muscle mounding 32 HP:0003719
36 bradycardia 32 HP:0001662
37 prominent umbilicus 32 HP:0001544
38 dilatation 32 HP:0002617
39 elevated hepatic transaminase 32 HP:0002910

UMLS symptoms related to Lipodystrophy, Congenital Generalized, Type 4:


constipation, generalized muscle weakness, myalgia, muscular stiffness

GenomeRNAi Phenotypes related to Lipodystrophy, Congenital Generalized, Type 4 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Reduced mammosphere formation GR00396-S 9.1 CAV1 CAV3 CEBPA LMNA SCD SCD5

MGI Mouse Phenotypes related to Lipodystrophy, Congenital Generalized, Type 4:

46 (show all 15)
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.31 ADIPOQ AGL AGPAT2 ATG5 BSCL2 CAV1
2 homeostasis/metabolism MP:0005376 10.25 ADIPOQ AGL AGPAT2 ATG5 BSCL2 CAV1
3 cellular MP:0005384 10.21 ADIPOQ ATG5 BSCL2 CAV1 CAV3 CAVIN1
4 growth/size/body region MP:0005378 10.2 ADIPOQ AGPAT2 ATG5 BSCL2 CAV1 CAVIN1
5 adipose tissue MP:0005375 10.15 ADIPOQ AGPAT2 ATG5 BSCL2 CAV1 CEBPA
6 cardiovascular system MP:0005385 10.13 ADIPOQ ATG5 BSCL2 CAV1 CAV3 CAVIN1
7 endocrine/exocrine gland MP:0005379 10.08 ADIPOQ AGPAT2 ATG5 BSCL2 CAV1 CEBPA
8 immune system MP:0005387 10.06 ADIPOQ AGPAT2 ATG5 BSCL2 CAV1 CAV3
9 mortality/aging MP:0010768 10.03 ADIPOQ AGL AGPAT2 ATG5 BSCL2 CAV1
10 digestive/alimentary MP:0005381 9.97 AGPAT2 ATG5 BSCL2 CAV1 CEBPA LMNA
11 liver/biliary system MP:0005370 9.97 ADIPOQ AGL AGPAT2 ATG5 BSCL2 CAV1
12 integument MP:0010771 9.91 ADIPOQ AGPAT2 BSCL2 CAV1 CEBPA LMNA
13 muscle MP:0005369 9.76 ADIPOQ AGL ATG5 CAV1 CAV3 CAVIN1
14 renal/urinary system MP:0005367 9.61 ADIPOQ AGPAT2 ATG5 BSCL2 CAV1 CAVIN1
15 respiratory system MP:0005388 9.17 ADIPOQ AGL ATG5 CAV1 CAVIN1 CEBPA

Drugs & Therapeutics for Lipodystrophy, Congenital Generalized, Type 4

Search Clinical Trials , NIH Clinical Center for Lipodystrophy, Congenital Generalized, Type 4

Genetic Tests for Lipodystrophy, Congenital Generalized, Type 4

Genetic tests related to Lipodystrophy, Congenital Generalized, Type 4:

# Genetic test Affiliating Genes
1 Lipodystrophy, Congenital Generalized, Type 4 29 CAVIN1

Anatomical Context for Lipodystrophy, Congenital Generalized, Type 4

MalaCards organs/tissues related to Lipodystrophy, Congenital Generalized, Type 4:

41
Liver, Skin, Smooth Muscle, Skeletal Muscle

Publications for Lipodystrophy, Congenital Generalized, Type 4

Articles related to Lipodystrophy, Congenital Generalized, Type 4:

# Title Authors Year
1
Post Mortem Findings in a Young Male with Congenital Generalized Lipodystrophy, Type 4 due to CAVIN1 mutations. ( 30476128 )
2018
2
Spectrum of clinical manifestations in two young Turkish patients with congenital generalized lipodystrophy type 4. ( 27167729 )
2016
3
Congenital generalized lipodystrophy type 4 with muscular dystrophy: clinical and pathological manifestations in early childhood. ( 23489663 )
2013
4
Congenital generalized lipodystrophy, type 4 (CGL4) associated with myopathy due to novel PTRF mutations. ( 20684003 )
2010
5
A Japanese child with asymptomatic elevation of serum creatine kinase shows PTRF-CAVIN mutation matching with congenital generalized lipodystrophy type 4. ( 20638880 )
2010

Variations for Lipodystrophy, Congenital Generalized, Type 4

ClinVar genetic disease variations for Lipodystrophy, Congenital Generalized, Type 4:

6 (show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 CAVIN1 NM_012232.5: c.160delG deletion Pathogenic
2 CAVIN1 NM_012232.5: c.362dupT duplication Pathogenic
3 CAVIN1 NM_012232.5: c.526delG deletion Pathogenic
4 CAVIN1 NM_012232.5: c.696dupC duplication Pathogenic
5 CAVIN1 NM_012232.5: c.135delG deletion Pathogenic
6 CAVIN1 NM_012232.5(CAVIN1): c.478_481dup (p.Lys161Serfs) duplication Pathogenic GRCh38 Chromosome 17, 42405379: 42405382
7 CAVIN1 NM_012232.5(CAVIN1): c.478_481dup (p.Lys161Serfs) duplication Pathogenic GRCh37 Chromosome 17, 40557397: 40557400
8 CAVIN1 NM_012232.5: c.518_521delAAGA deletion Pathogenic
9 CAVIN1 NM_012232.5(CAVIN1): c.471+1G> T single nucleotide variant Pathogenic rs866504928 GRCh37 Chromosome 17, 40574644: 40574644
10 CAVIN1 NM_012232.5(CAVIN1): c.471+1G> T single nucleotide variant Pathogenic rs866504928 GRCh38 Chromosome 17, 42422626: 42422626
11 CAVIN1 NM_012232.5(CAVIN1): c.199C> T (p.Gln67Ter) single nucleotide variant Likely pathogenic GRCh38 Chromosome 17, 42422899: 42422899
12 CAVIN1 NM_012232.5(CAVIN1): c.199C> T (p.Gln67Ter) single nucleotide variant Likely pathogenic GRCh37 Chromosome 17, 40574917: 40574917

Expression for Lipodystrophy, Congenital Generalized, Type 4

Search GEO for disease gene expression data for Lipodystrophy, Congenital Generalized, Type 4.

Pathways for Lipodystrophy, Congenital Generalized, Type 4

GO Terms for Lipodystrophy, Congenital Generalized, Type 4

Cellular components related to Lipodystrophy, Congenital Generalized, Type 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum membrane GO:0005789 9.7 AGPAT2 BSCL2 CAV1 RTN3 RTN4 SCD
2 membrane raft GO:0045121 9.56 CAV1 CAV3 CAVIN1 SLC2A1
3 integral component of endoplasmic reticulum membrane GO:0030176 9.54 BSCL2 RTN4 SCD
4 sarcolemma GO:0042383 9.5 CAV1 CAV3 SLC2A1
5 endoplasmic reticulum GO:0005783 9.32 ADIPOQ AGPAT2 BSCL2 CAV1 CAV3 CAVIN1
6 caveola GO:0005901 9.26 CAV1 CAV3 CAVIN1 SLC2A1
7 membrane GO:0016020 10.22 AGPAT2 ATG5 BSCL2 CAV1 CAV3 CAVIN1
8 integral component of membrane GO:0016021 10.17 AGPAT2 BSCL2 CAV1 CAV3 RTN3 RTN4

Biological processes related to Lipodystrophy, Congenital Generalized, Type 4 according to GeneCards Suite gene sharing:

(show all 22)
# Name GO ID Score Top Affiliating Genes
1 response to hypoxia GO:0001666 9.78 ADIPOQ CAV1 SLC2A1
2 glucose homeostasis GO:0042593 9.75 ADIPOQ CAV3 CEBPA
3 brown fat cell differentiation GO:0050873 9.6 ADIPOQ CEBPA
4 negative regulation of MAPK cascade GO:0043409 9.59 CAV1 CAV3
5 lipid storage GO:0019915 9.58 BSCL2 CAV1
6 negative regulation of phagocytosis GO:0050765 9.57 ADIPOQ ATG5
7 unsaturated fatty acid biosynthetic process GO:0006636 9.56 SCD SCD5
8 negative regulation of nitric-oxide synthase activity GO:0051001 9.55 CAV1 CAV3
9 negative regulation of potassium ion transmembrane transport GO:1901380 9.54 CAV1 CAV3
10 fatty-acyl-CoA biosynthetic process GO:0046949 9.52 SCD SCD5
11 ventricular cardiac muscle cell development GO:0055015 9.51 ATG5 LMNA
12 negative regulation of MAP kinase activity GO:0043407 9.5 ADIPOQ CAV1 CAV3
13 L-ascorbic acid metabolic process GO:0019852 9.49 SLC2A1 SLC2A3
14 endoplasmic reticulum tubular network organization GO:0071786 9.48 RTN3 RTN4
15 regulation of cardiac muscle cell action potential involved in regulation of contraction GO:0098909 9.46 CAV1 CAV3
16 caveola assembly GO:0070836 9.43 CAV1 CAV3
17 carbohydrate transport GO:0008643 9.43 SLC2A1 SLC2A14 SLC2A3
18 dehydroascorbic acid transport GO:0070837 9.4 SLC2A1 SLC2A3
19 endoplasmic reticulum tubular network formation GO:0071787 9.37 RTN3 RTN4
20 positive regulation of cold-induced thermogenesis GO:0120162 9.26 ADIPOQ BSCL2 CAV1 SCD
21 monounsaturated fatty acid biosynthetic process GO:1903966 9.16 SCD SCD5
22 glucose transmembrane transport GO:1904659 8.8 SLC2A1 SLC2A14 SLC2A3

Molecular functions related to Lipodystrophy, Congenital Generalized, Type 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transmembrane transporter activity GO:0022857 9.58 SLC2A1 SLC2A14 SLC2A3
2 nitric-oxide synthase binding GO:0050998 9.37 CAV1 CAV3
3 dehydroascorbic acid transmembrane transporter activity GO:0033300 9.32 SLC2A1 SLC2A3
4 oxidoreductase activity, acting on paired donors, with oxidation of a pair of donors resulting in the reduction of molecular oxygen to two molecules of water GO:0016717 9.26 SCD SCD5
5 stearoyl-CoA 9-desaturase activity GO:0004768 9.16 SCD SCD5
6 glucose transmembrane transporter activity GO:0005355 9.13 SLC2A1 SLC2A14 SLC2A3
7 D-glucose transmembrane transporter activity GO:0055056 8.8 SLC2A1 SLC2A14 SLC2A3

Sources for Lipodystrophy, Congenital Generalized, Type 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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