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Arrhythmogenic right ventricular dysplasia, familial, 10

General Information (adopted from Orphanet):

Synonyms, Signs:	ARVD10 ARVC10 Arrhythmogenic right ventricular cardiomyopathy 10
Number of Symptoms	28
OrphanetNr:
OMIM Id:	610193
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence:	No data available.
Inheritance:	Monogenic Autosomal dominant 16773573 [IBIS]
Age of onset:	Childhood Adolescent Adult 16773573 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases:

Familial isolated arrhythmogenic right ventricular dysplasia
-Rare cardiac disease
-Rare genetic disease

Comment:

ARVC10 is caused by mutation in DSG2 (PMID:17105751, PMID:16505173).

Symptom Information: Sort by abundance

	Symptom Information	Symptom	Abundance	Frequency	Pubmed	Source	DB Freq
1	(HPO:0002094)	Dyspnea			27055156	IBIS	132 / 7739
2	(HPO:0005133)	Right ventricular dilatation	Frequent	66% n=9	17105751	IBIS	14 / 7739
3	(HPO:0011663)	Right ventricular cardiomyopathy			16773573	IBIS	17 / 7739
4	(MedDRA:10067282)	Right atrial dilatation			16505173	IBIS	8 / 7739
5	(MedDRA:10071436)	Systolic dysfunction			17105751	IBIS	13 / 7739
6	(MedDRA:10050510)	Ventricular hypokinesia			17105751	IBIS	5 / 7739
7	(HPO:0003115)	Abnormal EKG			16773573	IBIS	44 / 7739
8	(HPO:0012250)	ST segment depression			16505173	IBIS	7 / 7739
9	(HPO:0005135)	EKG: T-wave abnormalities			16505173	IBIS	19 / 7739
10	(HPO:0010872)	EKG: T-wave inversion	Occadional	26% n=9	16773573	IBIS	19 / 7739
11	(HPO:0006677)	Prolonged QRS complex			16505173	IBIS	16 / 7739
12	(HPO:0003116)	Abnormal echocardiogram			16505173	IBIS	33 / 7739
13	(HPO:0012666)	Severely reduced ejection fraction			17105751	IBIS	9 / 7739
14	(HPO:0011712)	Right bundle branch block			16505173	IBIS	34 / 7739
15	(HPO:0001962)	Palpitations			16505173	IBIS	62 / 7739
16	(HPO:0004756)	Ventricular tachycardia			16773573	IBIS	55 / 7739
17	(HPO:0004308)	Ventricular arrhythmia			16773573	IBIS	46 / 7739
18	(HPO:0006682)	Ventricular extrasystoles			17105751	IBIS	25 / 7739
19	(HPO:0011713)	Left bundle branch block			16505173	IBIS	30 / 7739
20	(HPO:0001635)	Congestive heart failure			17105751	IBIS	232 / 7739
21	(HPO:0001645)	Sudden cardiac death	Frequent	66% n=9	17105751	IBIS	84 / 7739
22	(HPO:0001279)	Syncope			17105751	IBIS	94 / 7739
23	(HPO:0100749)	Chest pain			17105751	IBIS	92 / 7739
24	(HPO:0002617)	Aneurysm			16505173	IBIS	34 / 7739
25	(MedDRA:10036653)	Presyncope			17105751	IBIS	4 / 7739
26	(MedDRA:10048815)	Sinus rhythm			17105751	IBIS	3 / 7739
27	(OMIM)	Fibrofatty replacement of right ventricular myocardium			16773573	IBIS	11 / 7739
28	(OMIM)	Left ventricular enlargement	Occasional	25% n=9	17105751	IBIS	9 / 7739

Associated genes:

DSG2;

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference
DSG2	rs121913007	pathogenic	RCV000018304.29
DSG2	rs121913009	pathogenic	RCV000018306.27
DSG2	rs121913011	pathogenic	RCV000018308.27
DSG2	rs121913012	pathogenic	RCV000018309.27
DSG2	rs121913013	pathogenic	RCV000018311.23
DSG2	rs200484060	likely pathogenic	RCV000168632.1
DSG2	rs397516703	likely pathogenic	RCV000037271.2
DSG2	rs397516706	likely pathogenic	RCV000037297.2
DSG2	rs397516709	likely pathogenic	RCV000037309.2
DSG2	rs397516712	likely pathogenic	RCV000037320.2
DSG2	rs553299589	likely pathogenic	RCV000168625.1
DSG2	rs553299589	likely pathogenic	RCV000168629.1
DSG2	rs730880347	likely pathogenic	RCV000155624.1

Additional Information:

Molecular genetics OMIM

Pilichou et al. (2006) analyzed the DSG2 gene in 54 probands of Italian descent with arrhythmogenic right ventricular cardiomyopathy who were negative for mutations in the TGFB3 (190230), DSP (125647), and PKP2 (602861) genes, and identified 5 missense ... Pilichou et al. (2006) analyzed the DSG2 gene in 54 probands of Italian descent with arrhythmogenic right ventricular cardiomyopathy who were negative for mutations in the TGFB3 (190230), DSP (125647), and PKP2 (602861) genes, and identified 5 missense mutations, 2 insertion-deletions, 1 nonsense mutation, and 1 splice site mutation. The mutations were found in heterozygosity in 7 probands (see, e.g., 125671.0006) and in compound heterozygosity in 1 proband (125671.0007-125671.0008). None of the patients had effort-induced polymorphic ventricular arrhythmias or gross skin/hair abnormalities. Endomyocardial biopsies performed in 5 mutation-positive patients revealed a mean area of residual myocardium of approximately 47%, fibrous tissue of 24%, and fatty tissue of 20%. Electron microscopy in 3 of the biopsied patients revealed a decreased desmosome number, intercalated disc paleness, and intercellular gap widening. Awad et al. (2006) identified 33 cases of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) in which no mutation in the PKP2 or DSP genes had been found. Amplification and sequencing of the exonic and adjacent intronic sequence of the entire DSG2 gene identified mutations in 4 individuals. Three of the 4 probands had a single, heterozygous missense mutation in DSG2. The fourth proband had a missense mutation on 1 DSG2 allele and a nonsense mutation on the other (see 125671.0001). His unaffected mother and sister shared the nonsense mutation. Awad et al. (2006) suggested that this could indicate incomplete penetrance, or that this mutation is insufficient to result in ARVD/C in isolation. Syrris et al. (2007) sequenced the DSG2 gene in 86 Caucasian ARVC patients known to be negative for mutations in the DSP, PKP2, and JUP (173325) genes and detected 8 mutations in 9 probands (see, e.g., V55M, 125671.0009); the mutations were not found in 400 control chromosomes. Clinical evaluation of 24 family members with DSG2 mutations demonstrated penetrance of 58% to 75%, depending on the criteria used. Morphologic abnormalities of the right ventricle were evident in 66% of mutation carriers, left ventricular involvement in 25%, and classic right precordial T-wave inversion in only 26%. Sustained ventricular arrhythmia was present in 8%, and a family history of sudden death or aborted sudden death in 66%. Syrris et al. (2007) concluded that mutations in DSG2 show a high degree of penetrance with variable severity of expression; regarding the low prevalence of classic ECG changes, the authors suggested that current diagnostic criteria be expanded to account for left ventricular disease, childhood disease expression, and incomplete penetrance.

Symptoms & Signs

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