CREST syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: Calcinosis-Raynaud phenomenon-esophageal involvement-sclerodactyly-telangiectasia
Systemic sclerosis, susceptibility to CREST syndrome, included
Limited cutaneous SSc (lcSSc) [IBIS]
Number of Symptoms 57
OrphanetNr: 90290
OMIM Id: 181750
ICD-10: M34.1
UMLs: C0206138
MeSH: D017675
MedDRA: 10011380
Snomed: 31848007

Prevalence, inheritance and age of onset:

Prevalence: <= 9 of 100 000
Inheritance:
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Systemic inflammatory disease associated with an acquired peripheral neuropathy
 -Rare neurologic disease
Systemic sclerosis
 -Rare cardiac disease
 -Rare renal disease
 -Rare respiratory disease
 -Rare skin disease
 -Rare systemic or rheumatologic disease

Comment:

As a limited form of sclerodermy, CREST syndrome is characterized by calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia, which determine the acronym CREST (PMID:24142114). Calcifications, Raynaud’s phenomenon, esophageal hypomotility, sclerodactyly, and telangiectasia (CREST) syndrome can be considered as a lcSSc (limited cutaneous systemic sclerosis). This subset was first described as a benign form of SSc (systemic sclerosis). CREST patients could have three, four, or all five of the syndrome features, and the components were probably never meant to serve as criteria for a special subset of SSc patients. Features of CREST occur with time irrespective of other disease characteristics. Moreover, calcifications, Raynaud’s phenomenon, esophageal hypomotility, and telangiectasia are also common in dcSSc (diffuse cutaneous SS). Therefore, the use of CREST to define a subset of SSc patients is not helpful and may in fact be confusing albeit some lcSSc patients sometimes have a particular presentation with many calcifications and lots of telangiectasia. CREST (calcinosis, Raynaud’s phenomenon, esophageal involvement, sclerodactyly, and telangiectasia) is a synonym for lcSSc. In addition to the criteria for lSSc, lcSSc patients must demonstrate cutaneous involvement distal to the elbows, knees, and clavicles. Put the other way round, skin tautness of the fingers, hands, forearms, legs, feet, toes, neck, and face in the absence of skin tautness of the arms, chest, abdomen, back, or thighs (which defines dcSSc), in addition to the criteria for lSSc, defines lcSSc. Also, lcSSc can overlap with any other disease (including type I diabetes mellitus) (PMID:20143182). Anticentromere antibodies (ACA) and anti-topoisomerase I (anti-topo I) were found primarily in patients with scleroderma, CREST syndrome, and Raynaud's phenomenon (PMID:2833902).

Symptom Information: Sort by abundance 

1
 (HPO:0002027) Abdominal pain 26607041 IBIS 184 / 7739
2
 (HPO:0002239) Gastrointestinal hemorrhage 9732924 IBIS 97 / 7739
3
 (HPO:0002092) Pulmonary hypertension Occasional [Orphanet] 11669165 IBIS 109 / 7739
4
 (HPO:0002093) Respiratory insufficiency Frequent [Orphanet] 16278765 IBIS 410 / 7739
5
 (HPO:0001637) Abnormality of the myocardium 27169738 IBIS 76 / 7739
6
 (HPO:0001697) Abnormality of the pericardium 27169738 IBIS 52 / 7739
7
 (HPO:0011675) Arrhythmia 24142114 IBIS 226 / 7739
8
 (HPO:0002633) Vasculitis 22387650 IBIS 12 / 7739
9
 (HPO:0000969) Edema Very frequent [Orphanet] 16278765 IBIS 117 / 7739
10
 (HPO:0002960) Autoimmunity Very frequent [Orphanet] 16278765 IBIS 78 / 7739
11
 (HPO:0100324) Scleroderma 16278765 IBIS 6 / 7739
12
 (HPO:0002725) Systemic lupus erythematosus Occasional [IBIS] 11.1% (n=54) 2833902 IBIS 14 / 7739
13
 (HPO:0003761) Calcinosis Frequent [IBIS] 24142114 IBIS 12 / 7739
14
 (HPO:0100614) Myositis Rare [IBIS] 5.6 % (n=54) 2833902 IBIS 21 / 7739
15
 (HPO:0001324) Muscle weakness 24142114 IBIS 859 / 7739
16
 (MedDRA:10007697) Carpal tunnel syndrome 24142114 IBIS 16 / 7739
17
 (HPO:0007141) Sensorimotor neuropathy 22387650 IBIS 27 / 7739
18
 (HPO:0003401) Paresthesia 24142114 IBIS 42 / 7739
19
 (HPO:0012181) Entrapment neuropathy 24142114 IBIS 1 / 7739
20
 (HPO:0001251) Ataxia 22387650 IBIS 413 / 7739
21
 (HPO:0012378) Fatigue 26607041 IBIS 50 / 7739
22
 (HPO:0001337) Tremor 22387650 IBIS 200 / 7739
23
 (HPO:0002015) Dysphagia Very frequent [IBIS] Frequent [Orphanet] 24142114 IBIS 301 / 7739
24
 (HPO:0012531) Pain 24142114 IBIS 9 / 7739
25
 (HPO:0002829) Arthralgia 24142114 IBIS 79 / 7739
26
 (HPO:0001370) Rheumatoid arthritis Rare [IBIS] 5.6 % (n=54) 2833902 IBIS 12 / 7739
27
 (HPO:0100633) Esophagitis 16278765 IBIS 7 / 7739
28
 (HPO:0002020) Gastroesophageal reflux 16278765 IBIS 101 / 7739
29
 (HPO:0002592) Gastric ulcer Very frequent [Orphanet] 9732924 IBIS 39 / 7739
30
 (HPO:0005263) Gastritis 9732924 IBIS 9 / 7739
31
 (HPO:0100771) Hypoperistalsis 16278765 IBIS 5 / 7739
32
 (HPO:0004398) Peptic ulcer 9732924 IBIS 7 / 7739
33
 (HPO:0002613) Biliary cirrhosis 24142114 IBIS 11 / 7739
34
 (HPO:0000951) Abnormality of the skin Very frequent [IBIS] Very frequent [Orphanet] 20143182 IBIS 147 / 7739
35
 (HPO:0000980) Pallor 20143182 IBIS 52 / 7739
36
 (HPO:0000961) Cyanosis 20143182 IBIS 60 / 7739
37
 (HPO:0010783) Erythema 20143182 IBIS 138 / 7739
38
 (HPO:0000988) Skin rash 16278765 IBIS 98 / 7739
39
 (HPO:0200042) Skin ulcer Frequent [Orphanet] 16278765 IBIS 138 / 7739
40
 (HPO:0001072) Thickened skin 24142114 IBIS 87 / 7739
41
 (HPO:0011838) Sclerodactyly Very frequent [IBIS] 24142114 IBIS 8 / 7739
42
 (HPO:0100579) Mucosal telangiectasiae Frequent [Orphanet] 9732924 IBIS 10 / 7739
43
 (MedDRA:10068057) Dependent rubor 24142114 IBIS 1 / 7739
44
 (HPO:0001009) Telangiectasia Very frequent [IBIS] 24142114 IBIS 46 / 7739
45
 (HPO:0100585) Telangiectasia of the skin Frequent [Orphanet] 16278765 IBIS 66 / 7739
46
 (HPO:0004930) Abnormality of the pulmonary vasculature 27169738 IBIS 3 / 7739
47
 (HPO:0001873) Thrombocytopenia 21982887 IBIS 224 / 7739
48
 (HPO:0040078) Axonal degeneration 22387650 IBIS 10 / 7739
49
 (HPO:0030151) Cholangitis 26607041 IBIS 10 / 7739
50
 (MedDRA:10016642) Fibrosis 16278765 IBIS 9 / 7739
51
 (MedDRA:10061156) Finger deformity 24142114 IBIS 5 / 7739
52
 (MedDRA:10052178) Lymphocytic lymphoma 21982887 IBIS 2 / 7739
53
 (MedDRA:10042953) Systemic sclerosis 24142114 IBIS 1 / 7739
54
 (OMIM) Anticentromere and other antibodies 2833902 IBIS 1 / 7739
55
 (OMIM) Edema, nonpitting 16278765 IBIS 3 / 7739
56
 (OMIM) Increased risk for cancer 24142114 IBIS 3 / 7739
57
 (OMIM) Raynaud syndrome Very frequent [IBIS] 24142114 IBIS 3 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Systemic sclerosis is a clinically heterogeneous connective tissue disorder characterized by immune activation, vascular damage, and fibrosis of the skin and major internal organs. Clinical and experimental data suggest that the disorder is multifactorial, involving both genetic and ...
Clinical Description OMIM Greger (1975) described 3 males, including father and son, with progressive systemic scleroderma (systemic sclerosis) in an inbred triracial isolate of southern Maryland, known as the Brandywine group. A sister of the aforementioned son had rheumatoid arthritis. The ...