Generalized congenital lipodystrophy with myopathy

General Information (adopted from Orphanet):

Synonyms, Signs: LIPODYSTROPHY, BERARDINELLI-SEIP CONGENITAL, TYPE 4, WITH MUSCULAR DYSTROPHY
CGL4
GCL4
Berardinelli-Seip Congenital Lipodystrophy, type 4
Generalized congenital lipodystrophy type 4
Number of Symptoms 66
OrphanetNr: 228429
OMIM Id: 613327
ICD-10: E88.1
G71.0
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: < 0.1 of 100 000
Inheritance: Autosomal recessive
25721873 [IBIS]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Genetic cardiac rhythm disease
 -Rare cardiac disease
 -Rare genetic disease
Genetic lipodystrophy
 -Rare endocrine disease
 -Rare genetic disease
 -Rare skin disease
Insulin-resistance syndrome
 -Rare endocrine disease
 -Rare genetic disease
Non-dystrophic myopathy
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Generalized congenital lipodystrophy with myopathy or CGL4 is sub-type of congenital generalized lipodystrophies, a heterogeneous group of rare monogenic disorders that are all characterized by loss of subcutaneous fat deposition, enlarged fatty liver, impaired triglyceride metabolism, acanthosis nigricans and early diabetes. CGL4 is characterized by muscular dystrophy, cervical spine instability and cardiac abnormalities (PMID:25721873).

Symptom Information: Sort by abundance 

1
 (HPO:0003198) Myopathy Frequent [IBIS] 25721873 IBIS 151 / 7739
2
 (HPO:0001531) Failure to thrive in infancy 25721873 IBIS 26 / 7739
3
 (HPO:0004756) Ventricular tachycardia 20684003 IBIS 55 / 7739
4
 (HPO:0001538) Protuberant abdomen 20684003 IBIS 36 / 7739
5
 (HPO:0001387) Joint stiffness 20684003 IBIS 322 / 7739
6
 (HPO:0002013) Vomiting 20684003 IBIS 191 / 7739
7
 (HPO:0001324) Muscle weakness 19726876 IBIS 859 / 7739
8
 (HPO:0001433) Hepatosplenomegaly 19726876 IBIS 78 / 7739
9
 (HPO:0004308) Ventricular arrhythmia 20684003 IBIS 46 / 7739
10
 (HPO:0003467) Atlantoaxial instability 20684003 IBIS 6 / 7739
11
 (HPO:0004349) Reduced bone mineral density 25721873 IBIS 165 / 7739
12
 (HPO:0009059) Congenital generalized lipodystrophy Frequent [IBIS] 25721873 IBIS 2 / 7739
13
 (HPO:0000411) Protruding ear 25721873 IBIS 140 / 7739
14
 (HPO:0000177) Abnormality of upper lip 25721873 IBIS 3 / 7739
15
 (HPO:0000307) Pointed chin 25721873 IBIS 45 / 7739
16
 (HPO:0000535) Sparse and thin eyebrow 25721873 IBIS 76 / 7739
17
 (HPO:0000527) Long eyelashes 25721873 IBIS 46 / 7739
18
 (HPO:0000336) Prominent supraorbital ridges 25721873 IBIS 45 / 7739
19
 (HPO:0008897) Postnatal growth retardation 25721873 IBIS 113 / 7739
20
 (HPO:0003077) Hyperlipidemia 25721873 IBIS 37 / 7739
21
 (HPO:0001249) Intellectual disability 25721873 IBIS 1089 / 7739
22
 (HPO:0002194) Delayed gross motor development 25721873 IBIS 37 / 7739
23
 (HPO:0001258) Spastic paraplegia 25721873 IBIS 97 / 7739
24
 (HPO:0001762) Talipes equinovarus 25721873 IBIS 309 / 7739
25
 (HPO:0003758) Reduced subcutaneous adipose tissue Very frequent [IBIS] 25721873 IBIS 27 / 7739
26
 (HPO:0010646) Cervical spine instability Frequent [IBIS] 25721873 IBIS 2 / 7739
27
 (HPO:0001015) Prominent superficial veins 20684003 IBIS 7 / 7739
28
 (HPO:0000821) Hypothyroidism 25721873 IBIS 141 / 7739
29
 (HPO:0008887) Adipose tissue loss Very frequent [IBIS] 25721873 IBIS 4 / 7739
30
 (HPO:0002015) Dysphagia 20684003 IBIS 301 / 7739
31
 (HPO:0000842) Hyperinsulinemia 20684003 IBIS 39 / 7739
32
 (HPO:0001371) Flexion contracture 20684003 IBIS 220 / 7739
33
 (HPO:0002650) Scoliosis 19726876 IBIS 705 / 7739
34
 (HPO:0000939) Osteoporosis 20300641 IBIS 129 / 7739
35
 (HPO:0000938) Osteopenia 20300641 IBIS 138 / 7739
36
 (HPO:0003306) Spinal rigidity 20300641 IBIS 30 / 7739
37
 (HPO:0003307) Hyperlordosis 20300641 IBIS 122 / 7739
38
 (HPO:0002019) Constipation 19726876 IBIS 194 / 7739
39
 (HPO:0001397) Hepatic steatosis 20684003 IBIS 75 / 7739
40
 (HPO:0002021) Pyloric stenosis 20684003 IBIS 51 / 7739
41
 (HPO:0002240) Hepatomegaly Frequent [IBIS] 25721873 IBIS 467 / 7739
42
 (HPO:0001544) Prominent umbilicus 20684003 IBIS 4 / 7739
43
 (HPO:0000956) Acanthosis nigricans Frequent [IBIS] 25721873 IBIS 54 / 7739
44
 (HPO:0001657) Prolonged QT interval Rare [IBIS] 20300641 IBIS 33 / 7739
45
 (HPO:0001662) Bradycardia 20300641 IBIS 41 / 7739
46
 (HPO:0001649) Tachycardia 20684003 IBIS 53 / 7739
47
 (HPO:0005110) Atrial fibrillation 19726876 IBIS 71 / 7739
48
 (HPO:0011675) Arrhythmia 19726876 IBIS 226 / 7739
49
 (HPO:0003236) Elevated serum creatine phosphokinase 20684003 IBIS 214 / 7739
50
 (HPO:0000855) Insulin resistance 20684003 IBIS 32 / 7739
51
 (HPO:0002155) Hypertriglyceridemia Frequent [IBIS] 20684003 IBIS 67 / 7739
52
 (HPO:0003546) Exercise intolerance 20300641 IBIS 62 / 7739
53
 (HPO:0003701) Proximal muscle weakness 19726876 IBIS 105 / 7739
54
 (HPO:0003552) Muscle stiffness 25721873 IBIS 23 / 7739
55
 (HPO:0003719) Muscle mounding 20684003 IBIS 4 / 7739
56
 (HPO:0003326) Myalgia 19726876 IBIS 143 / 7739
57
 (HPO:0003712) Skeletal muscle hypertrophy 19726876 IBIS 42 / 7739
58
 (HPO:0003560) Muscular dystrophy Frequent [IBIS] 25721873 IBIS 88 / 7739
59
 (HPO:0009125) Lipodystrophy 25721873 IBIS 54 / 7739
60
 (OMIM) Prominent muscular appearance 20684003 IBIS 1 / 7739
61
 (OMIM) Percussion-induced muscle mounding (muscle rippling) 20300641 IBIS 1 / 7739
62
 (OMIM) Decreased caveolae in muscle tissue 20300641 IBIS 1 / 7739
63
 (OMIM) Acromegaloid features 20684003 IBIS 1 / 7739
64
 (OMIM) Atlanto-axial instability 20684003 IBIS 1 / 7739
65
 (OMIM) Protruding abdomen 20684003 IBIS 2 / 7739
66
 (OMIM) Loss of subcutaneous fat, generalized 25721873 IBIS 2 / 7739

Associated genes:

PTRF;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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 ...
Clinical Description OMIM Rajab et al. (2002) described 10 patients from Oman who had congenital generalized lipodystrophy as well as striking abnormalities in both skeletal and nonskeletal muscle, including reduced exercise tolerance and percussion myoedema. Ghanem (1993) had described percussion myoedema ...
Molecular genetics OMIM In 4 unrelated Japanese patients with congenital generalized lipodystrophy type 4 and muscular dystrophy, Hayashi et al. (2009) identified a homozygous truncating mutation in exon 2 of the PTRF gene (696insC; 603198.0001). A fifth Japanese patient was compound ...