Cardiodysrhythmic potassium-sensitive periodic paralysis

General Information (adopted from Orphanet):

Synonyms, Signs: PERIODIC PARALYSIS, POTASSIUM-SENSITIVE CARDIODYSRHYTHMIC TYPE
LONG QT SYNDROME 7
LQT7
ATS
Andersen syndrome
QT long syndrome type 7
Long QT syndrome 7
Andersen cardiodysrhythmic periodic paralysis
Andersen-tawil syndrome
Number of Symptoms 85
OrphanetNr: 37553
OMIM Id: 170390
ICD-10: G72.3
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 0.1 of 100 000 - PMID: 24383070 [IBIS]
Inheritance: Autosomal dominant
- PMID: 15911703 [IBIS]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Genetic cardiac rhythm disease
 -Rare cardiac disease
 -Rare genetic disease
Genetic muscular channelopathy
 -Rare genetic disease
Genetic periodic paralysis
 -Rare genetic disease
 -Rare neurologic disease
Muscular channelopathy
 -Rare neurologic disease
Periodic paralysis
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Cardiodysrhythmic potassium-sensitive periodic paralysis (Andersen-Tawil syndrome) is a sub-type of familial long QT syndrome. Patients with mutations in the KCNJ2 gene are designated as ATS type 1 (LQT7), whereas patients with unknown mutations are designated as ATS type 2 (PMID:24383070). Recently, a mutation in KCNJ5 has been described (PMID:24574546). It is characterized by cardiac arrhythima, muscle weakness (periodic paralysis) and craniofacial and skeletal anomalies (PMID:20301308).

Symptom Information: Sort by abundance 

1
(HPO:0000316) Hypertelorism Frequent [IBIS] 36% (n=36) 12163457 IBIS 644 / 7739
2
(HPO:0004322) Short stature 8080508 IBIS 1232 / 7739
3
(HPO:0001644) Dilated cardiomyopathy 24383070 IBIS 141 / 7739
4
(HPO:0005135) EKG: T-wave abnormalities Occasional [IBIS] 15911703 IBIS 19 / 7739
5
(HPO:0010872) EKG: T-wave inversion Rare [IBIS] 7% (n=96) 15911703 IBIS 19 / 7739
6
(HPO:0001657) Prolonged QT interval Very frequent [IBIS] 93% (n=15) 12163457 IBIS 33 / 7739
7
(HPO:0011675) Arrhythmia Very frequent [IBIS] 15911703 IBIS 226 / 7739
8
(HPO:0005150) Abnormal atrioventricular conduction Occasional [IBIS] 23% (n=96) 15911703 IBIS 16 / 7739
9
(HPO:0011705) First degree atrioventricular block Rare [IBIS] 7% (n=96) 15911703 IBIS 13 / 7739
10
(HPO:0011712) Right bundle branch block Occasional [IBIS] 9% (n=96) 15911703 IBIS 34 / 7739
11
(HPO:0001962) Palpitations Rare [IBIS] 5% (n=96) 15911703 IBIS 62 / 7739
12
(HPO:0004756) Ventricular tachycardia 26448239 IBIS 55 / 7739
13
(HPO:0004758) Effort-induced polymorphic ventricular tachycardias Frequent [IBIS] 24827800 IBIS 3 / 7739
14
(HPO:0004308) Ventricular arrhythmia Frequent [IBIS] 88% (n=17) 12163457 IBIS 46 / 7739
15
(HPO:0005147) Bidirectional ventricular ectopy 16419128 IBIS 2 / 7739
16
(HPO:0001664) Torsade de pointes Rare [IBIS] 3% (n=96) 15911703 IBIS 15 / 7739
17
(HPO:0006682) Ventricular extrasystoles Frequent [IBIS] 41% (n=96) 15911703 IBIS 25 / 7739
18
(HPO:0011713) Left bundle branch block Rare [IBIS] 2% (n=96) 15911703 IBIS 30 / 7739
19
(HPO:0001695) Cardiac arrest Rare [IBIS] 3% (n=96) 15911703 IBIS 87 / 7739
20
(HPO:0001645) Sudden cardiac death Rare [IBIS] 24383070 IBIS 84 / 7739
21
(HPO:0001279) Syncope Frequent [IBIS] 11% (n=96) 15911703 IBIS 94 / 7739
22
(HPO:0003236) Elevated serum creatine phosphokinase 8080508 IBIS 214 / 7739
23
(HPO:0100301) Muscle fiber tubular inclusions 8080508 IBIS 1 / 7739
24
(HPO:0003690) Limb muscle weakness 26448239 IBIS 41 / 7739
25
(HPO:0002486) Myotonia 24383070 IBIS 29 / 7739
26
(HPO:0003768) Periodic paralysis Frequent [IBIS] 50% (n=96) 15911703 IBIS 9 / 7739
27
(HPO:0008153) Periodic hypokalemic paresis 25284084 IBIS 4 / 7739
28
(HPO:0001328) Specific learning disability Rare [IBIS] 26448239 IBIS 114 / 7739
29
(HPO:0000716) Depression 16419128 IBIS 99 / 7739
30
(HPO:0100543) Cognitive impairment Rare [IBIS] 24383070 IBIS 230 / 7739
31
(HPO:0001315) Reduced tendon reflexes 25284084 IBIS 160 / 7739
32
(HPO:0002373) Febrile seizures 26448239 IBIS 37 / 7739
33
(HPO:0009803) Short phalanx of finger 16419128 IBIS 79 / 7739
34
(HPO:0004209) Clinodactyly of the 5th finger 16419128 IBIS 288 / 7739
35
(HPO:0009381) Short finger 16419128 IBIS 45 / 7739
36
(HPO:0001864) Clinodactyly of the 5th toe 16419128 IBIS 6 / 7739
37
(HPO:0001770) Toe syndactyly 16419128 IBIS 149 / 7739
38
(HPO:0004691) 2-3 toe syndactyly 16419128 IBIS 50 / 7739
39
(HPO:0011927) Short digit 16419128 IBIS 17 / 7739
40
(HPO:0001156) Brachydactyly syndrome 16419128 IBIS 180 / 7739
41
(HPO:0001159) Syndactyly Occasional [IBIS] 11% (n=36) 12163457 IBIS 140 / 7739
42
(HPO:0010743) Short metatarsal 16419128 IBIS 56 / 7739
43
(HPO:0007598) Bilateral single transverse palmar creases 16419128 IBIS 13 / 7739
44
(HPO:0010049) Short metacarpal 16419128 IBIS 99 / 7739
45
(HPO:0004279) Short palm 16419128 IBIS 323 / 7739
46
(HPO:0200055) Small hand 16419128 IBIS 71 / 7739
47
(HPO:0000347) Micrognathia Frequent [IBIS] 44% (n=36) 12163457 IBIS 426 / 7739
48
(HPO:0003778) Short mandibular rami 16419128 IBIS 7 / 7739
49
(HPO:0003779) Antegonial notching of mandible 16419128 IBIS 2 / 7739
50
(HPO:0000278) Retrognathia 26448239 IBIS 100 / 7739
51
(HPO:0009117) Aplasia/Hypoplasia of the maxilla 16419128 IBIS 18 / 7739
52
(HPO:0000327) Hypoplasia of the maxilla 16419128 IBIS 129 / 7739
53
(HPO:0005478) Prominent frontal sinuses 16419128 IBIS 1 / 7739
54
(HPO:0000268) Dolichocephaly 24383070 IBIS 144 / 7739
55
(HPO:0000337) Broad forehead 24383070 IBIS 116 / 7739
56
(HPO:0003691) Scapular winging 16419128 IBIS 51 / 7739
57
(HPO:0002650) Scoliosis Occasional [IBIS] 11% (n=36) 8080508 IBIS 705 / 7739
58
(HPO:0001388) Joint laxity 16419128 IBIS 117 / 7739
59
(HPO:0001999) Abnormal facial shape Very frequent [IBIS] 8080508 IBIS 169 / 7739
60
(HPO:0000272) Malar flattening 16419128 IBIS 277 / 7739
61
(HPO:0000325) Triangular face 16419128 IBIS 91 / 7739
62
(HPO:0000174) Abnormality of the palate 24383070 IBIS 298 / 7739
63
(HPO:0000175) Cleft palate Occasional [IBIS] 8% (n=36) 16419128 IBIS 349 / 7739
64
(HPO:0002705) High, narrow palate 16419128 IBIS 308 / 7739
65
(HPO:0006297) Hypoplasia of dental enamel 16419128 IBIS 64 / 7739
66
(HPO:0000696) Delayed eruption of permanent teeth 16419128 IBIS 12 / 7739
67
(HPO:0000677) Oligodontia 16419128 IBIS 41 / 7739
68
(HPO:0000219) Thin upper lip vermilion 16419128 IBIS 112 / 7739
69
(HPO:0000233) Thin vermilion border 16419128 IBIS 124 / 7739
70
(HPO:0000455) Broad nasal tip 16419128 IBIS 67 / 7739
71
(HPO:0000414) Bulbous nose 16419128 IBIS 63 / 7739
72
(HPO:0000445) Wide nose 24383070 IBIS 190 / 7739
73
(HPO:0000369) Low-set ears Frequent [IBIS] 39% (n=36) 12163457 IBIS 372 / 7739
74
(HPO:0001507) Growth abnormality 16419128 IBIS 36 / 7739
75
(HPO:0030084) Clinodactyly Frequent [IBIS] 64% (n=36) 12163457 IBIS 90 / 7739
76
(MedDRA:10072883) Brachydactyly 16419128 IBIS 153 / 7739
77
(MedDRA:10055032) Electrocardiogram U-wave abnormality Frequent [IBIS] 76% (n=17) 12163457 IBIS 2 / 7739
78
(OMIM) Anterior crossbite 16419128 IBIS 1 / 7739
79
(OMIM) Condylar resorption 16419128 IBIS 1 / 7739
80
(OMIM) Elongated roots with open apices 16419128 IBIS 1 / 7739
81
(OMIM) Facial asymmetry, mild 8080508 IBIS 5 / 7739
82
(OMIM) Gracile ribs 16419128 IBIS 1 / 7739
83
(OMIM) Learning disabilities, mild (some patients) 26448239 IBIS 1 / 7739
84
(OMIM) Prolonged QTc 8080508 IBIS 1 / 7739
85
(OMIM) Prominent U wave Frequent [IBIS] 76% (n=17) 12163457 IBIS 1 / 7739

Associated genes:

KCNJ2; KCNJ5;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
KCNJ2 rs104894575 pathogenic RCV000009473.4
KCNJ2 rs104894578 pathogenic RCV000009474.2
KCNJ2 rs104894579 pathogenic RCV000194837.1
KCNJ2 rs104894579 pathogenic RCV000009475.2
KCNJ2 rs104894580 pathogenic RCV000009478.2
KCNJ2 rs104894581 pathogenic RCV000009479.2
KCNJ2 rs104894582 pathogenic RCV000009480.2
KCNJ2 rs104894583 pathogenic RCV000009481.4
KCNJ2 rs104894585 pathogenic RCV000009483.2
KCNJ2 rs199473371 pathogenic RCV000157272.1
KCNJ2 rs199473384 pathogenic RCV000157273.1
KCNJ2 rs199473387 pathogenic RCV000023028.4
KCNJ2 rs199473650 pathogenic RCV000023027.2
KCNJ2 rs797044841 pathogenic RCV000192428.1
KCNJ2 rs797044842 pathogenic RCV000193904.1
KCNJ5 rs199830292 pathogenic RCV000193019.1
KCNJ5 rs387906778 pathogenic RCV000194572.1

Additional Information:

Description: (OMIM) Andersen-Tawil syndrome is an autosomal dominant multisystem channelopathy characterized by periodic paralysis, ventricular arrhythmias, and distinctive dysmorphic facial or skeletal features. Hypoplastic kidney and valvular heart disease have also been reported. The disorder shows marked intrafamilial variability and ...
Clinical Description OMIM Tawil et al. (1994) used the designation Andersen syndrome for a clinical triad consisting of potassium-sensitive periodic paralysis, ventricular ectopy, and dysmorphic features. (This Andersen syndrome is not to be confused with Andersen disease, type IV glycogen storage ...
Molecular genetics OMIM In a kindred with Andersen syndrome showing linkage to 17q23, Plaster et al. (2001) identified a missense mutation in the KCNJ2 gene (600681.0001). They identified 8 additional mutations in the KCNJ2 gene in unrelated patients with Andersen syndrome ...
Diagnosis GeneReviews The diagnosis of Andersen-Tawil syndrome (ATS) is suspected in individuals with either A or B: ...
Clinical Description GeneReviews Andersen-Tawil syndrome (ATS) is characterized by the triad of episodic flaccid muscle weakness, distinctive dysmorphic features, and ventricular arrhythmias and prolonged QT interval. Affected individuals present initially with either periodic paralysis or cardiac symptoms (palpitations and/or syncope) in the first or second decade [Tawil et al 1994, Tristani-Firouzi et al 2002]; however, prospective standardized natural history data are not yet available. ...
Genotype-Phenotype Correlations GeneReviews Individuals with clinically defined ATS are phenotypically indistinguishable, regardless of the presence of a KCNJ2 mutation (ATS1) or absence of a KCNJ2 mutation (ATS2) [Tristani-Firouzi et al 2002, Donaldson et al 2003]. ...
Differential Diagnosis GeneReviews Table 2. Long QT syndrome: OMIM Phenotypic Series...
Management GeneReviews To establish the extent of disease in an individual diagnosed with Andersen-Tawil syndrome (ATS), the following evaluations are recommended:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....