cms244c-T1

Table 1: Rare genetic cardiovascular diseases identified in

the outpatient clinic of a cardiology hospital in 2019.

Name of

rare genetic cardiovascular disease

ORPHAcode2

n

Prevalence

per 10,000

patients in

the outpatient

clinic

Type of

rare

disease*

Type of

genetic

disease

Marfan syndrome

558

178

56.5

Rare

Monogenic

Romano ward syndrome

(long QT syndrome type 1, 2, and 3)

101,016

79

25.1

Rare

Monogenic

Noonan syndrome

648

72

22.9

Rare

Monogenic

22q11.2 deletion syndrome

567

43

13.7

Rare

Chromosomal

Williams syndrome

904

42

13.3

Rare

Chromosomal

Loeys-Dietz syndrome

60,030

38

12.1

Unknown

Monogenic

Left ventricular noncompaction

54,260

29

9.2

Unknown

Monogenic

Turner syndrome

881

24

7.6

Rare

Chromosomal

Brugada syndrome (types 1, 2, and 3)

130

21

6.7

Rare

Monogenic

Familial isolated dilated cardiomyopathy

217,656

20

6.4

Rare

Monogenic

Holt-Oram syndrome

392

18

5.7

Ultrarare

Monogenic

Familial isolated arrhythmogenic

right ventricular dysplasia

154

16

5.1

Unknown

Monogenic

Supravalvular aortic stenosis

3,193

14

4.4

Rare

Monogenic

Classical Ehlers-Danlos syndrome

287

11

3.5

Rare

Monogenic

Familial thoracic aortic aneurysm

and aortic dissection

91,387

11

3.5

Ultrarare

Monogenic

Heterotaxia (visceral heterotaxy)

450

9

2.9

Rare

Monogenic

Neurofibromatosis type 1

636

9

2.9

Rare

Monogenic

Andersen-Tawil syndrome

37,553

8

2.5

Unknown

Monogenic

Tuberous sclerosis complex

805

8

2.5

Rare

Monogenic

Congenital

contractural arachnodactyly

115

6

1.9

Unknown

Monogenic

Jervell and Lange-Nielsen syndrome

768

6

1.9

Ultrarare

Monogenic

Vascular Ehlers-Danlos syndrome

286

6

1.9

Ultrarare

Monogenic

Hypermobile Ehlers-Danlos syndrome

285

5

1.6

Rare

Monogenic

Klippel-Feil syndrome

2,345

5

1.6

Ultrarare

Monogenic

CHARGE syndrome

138

4

1.3

Rare

Monogenic

Lown-Ganong-Levine syndrome

844

4

1.3

Ultrarare

Monogenic

Wolf-Hirschhorn syndrome

280

4

1.3

Rare

Chromosomal

Cardiofaciocutaneous syndrome

1,340

3

1

Unknown

Monogenic

Coffin-Lowry syndrome

192

3

1

Ultrarare

Monogenic

Cornelia de Lange syndrome

199

3

1

Ultrarare

Monogenic

Friedreich ataxia

95

3

1

Ultrarare

Monogenic

Hereditary hemorrhagic telangiectasia

774

3

1

Rare

Monogenic

Klippel-Trenaunay syndrome

90,308

3

1

Ultrarare

Monogenic

Sotos syndrome

821

3

1

Rare

Monogenic

Alagille syndrome

52

2

0.6

Ultrarare

Monogenic

Apert syndrome

87

2

0.6

Ultrarare

Monogenic

Crouzon syndrome

207

2

0.6

Ultrarare

Monogenic

Duchenne muscular dystrophy

98,896

2

0.6

Rare

Monogenic

Emery-Dreifuss dystrophy

261

2

0.6

Ultrarare

Monogenic

Frontonasal dysplasia

250

2

0.6

Unknown

Monogenic

Hereditary ATTR amyloidosis

271,861

2

0.6

Unknown

Monogenic

Johanson-Blizzard syndrome

2,315

2

0.6

Ultrarare

Monogenic

Kearns-Sayre syndrome

480

2

0.6

Ultrarare

Monogenic

MASS syndrome

156,532

2

0.6

Unknown

Monogenic

Noonan syndrome with

multiple lentigines (LEOPARD)

500

2

0.6

Unknown

Monogenic

Smith-Magenis syndrome

819

2

0.6

Rare

Monogenic

Spondylocostal dysostosis

1,797

2

0.6

Unknown

Monogenic

47,XYY syndrome

8

1

0.3

Rare

Chromosomal

Aarskog-Scott syndrome

915

1

0.3

Rare

Monogenic

Achondroplasia

15

1

0.3

Rare

Monogenic

Acute intermittent porphyria

79,276

1

0.3

Ultrarare

Monogenic

Arterial tortuosity syndrome

3,342

1

0.3

Ultrarare

Monogenic

Autosomal dominant interatrial communication

1,478

1

0.3

Unknown

Monogenic

Autosomal recessive

multiple pterygium syndrome

2,990

1

0.3

Ultrarare

Monogenic

Axenfeld-Rieger syndrome

782

1

0.3

Ultrarare

Monogenic

Becker muscular dystrophy

98,895

1

0.3

Ultrarare

Monogenic

Blackfan-Diamond anemia

124

1

0.3

Ultrarare

Monogenic

Carney complex

1,359

1

0.3

Unknown

Monogenic

Catecholaminergic

polymorphic ventricular tachycardia

3,286

1

0.3

Rare

Monogenic

Complex chromosomal

rearrangement; t(1;3)

263,708

1

0.3

Unknown

Chromosomal

Complex chromosomal

rearrangement; t(14;22)

263,708

1

0.3

Unknown

Chromosomal

Complex chromosomal

rearrangement; t(7;12)

263,708

1

0.3

Unknown

Chromosomal

Complex chromosomal

rearrangement; t(8;18)

263,708

1

0.3

Unknown

Chromosomal

Congenital heart block

60,041

1

0.3

Unknown

Monogenic

Costello syndrome

3,071

1

0.3

Ultrarare

Monogenic

Distal trisomy 18q

1,716

1

0.3

Unknown

Chromosomal

Distal trisomy 6p

1,745

1

0.3

Ultrarare

Chromosomal

Ellis Van Creveld syndrome

289

1

0.3

Unknown

Monogenic

Fabry disease

324

1

0.3

Rare

Monogenic

Familial atrial fibrillation

334

1

0.3

Unknown

Monogenic

Familial dilated cardiomyopathy

with conduction defect

due to LMNA mutation

300,751

1

0.3

Unknown

Monogenic

Fragile X syndrome

908

1

0.3

Rare

Monogenic

Incontinentia pigmenti

464

1

0.3

Ultrarare

Monogenic

Kabuki syndrome

2,322

1

0.3

Rare

Monogenic

Kallmann syndrome-heart disease

syndrome

2,326

1

0.3

Ultrarare

Monogenic

Kyphoscoliotic Ehlers-Danlos

syndrome

536,545

1

0.3

Unknown

Monogenic

Larsen syndrome

503

1

0.3

Ultrarare

Monogenic

McCune Albright syndrome

562

1

0.3

Ultrarare

Monogenic

Meckel syndrome

564

1

0.3

Rare

Monogenic

Mosaic trisomy 8

96,061

1

0.3

Unknown

Chromosomal

Mucopolysaccharidosis

type 2 (Hunter)

580

1

0.3

Ultrarare

Monogenic

Mucopolysaccharidosis

type 6 (Maroteaux-Lamy)

583

1

0.3

Ultrarare

Monogenic

Muenke syndrome

53,271

1

0.3

Rare

Monogenic

Multiminicore myopathy

598

1

0.3

Unknown

Monogenic

Oculopharyngeal muscular dystrophy

270

1

0.3

Ultrarare

Monogenic

Opitz GBBB syndrome

2,745

1

0.3

Ultrarare

Monogenic

Partial duplication of the long arm

of chromosome 13; t(13;14)

262,932

1

0.3

Unknown

Chromosomal

Partial duplication of the long arm

of chromosome 13; t(13;15)

262,932

1

0.3

Unknown

Chromosomal

Partial duplication of the short arm

of chromosome 11

262,785

1

0.3

Unknown

Chromosomal

Pfeiffer syndrome

710

1

0.3

Unknown

Monogenic

Pseudopseudohypoparathyroidism

79,445

1

0.3

Unknown

Monogenic

Robinow syndrome

97,360

1

0.3

Unknown

Monogenic

Rubinstein-Taybi syndrome

783

1

0.3

Ultrarare

Monogenic

Seckel syndrome

808

1

0.3

Ultrarare

Monogenic

Short QT syndrome

51,083

1

0.3

Unknown

Monogenic

Shprintzen-Goldberg syndrome

2,462

1

0.3

Ultrarare

Monogenic

Steinert myotonic dystrophy

273

1

0.3

Rare

Monogenic

Stickler syndrome

828

1

0.3

Rare

Monogenic

TARP syndrome

2,886

1

0.3

Ultrarare

Monogenic

Tel Hashomer

camptodactyly syndrome

3,292

1

0.3

Ultrarare

Monogenic

Tetrasomy 12p

(Pallister-Killian syndrome)

884

1

0.3

Rare

Chromosomal

Trisomy X

3,375

1

0.3

Rare

Chromosomal

TTR-related cardiac amyloidosis

85,451

1

0.3

Unknown

Monogenic

Van den Ende-Gupta syndrome

2,460

1

0.3

Ultrarare

Monogenic

CHARGE = coloboma, heart defects, atresia of the choanae, retardation of growth and development, genital abnormalities, and ear abnormalities.

ATTR = transthyretin-related amyloidosis.

MASS = mitral valve, aorta, skeletal, and skin.

LMNA = lamin.

GBBB = first letter from the last names of the families that was first diagnosed.

TARP = talipes equinovarus, atrial septal defect, robin sequence, and persistence of left superior vena cava.

TTR = transthyretin.

* According to the diseases prevalences in Orphanet;2 rare (< 1/2,000 - > 1/50,000),

ultrarare (≤ 1/50,000 - < 1/1’000,000), and unknown prevalence.

Table 1: Rare genetic cardiovascular diseases identified in the outpatient clinic of a cardiology hospital in 2019.
Name of rare genetic cardiovascular disease	ORPHAcode2	n	Prevalence per 10,000 patients in the outpatient clinic	Type of rare disease*	Type of genetic disease
Marfan syndrome	558	178	56.5	Rare	Monogenic
Romano ward syndrome (long QT syndrome type 1, 2, and 3)	101,016	79	25.1	Rare	Monogenic
Noonan syndrome	648	72	22.9	Rare	Monogenic
22q11.2 deletion syndrome	567	43	13.7	Rare	Chromosomal
Williams syndrome	904	42	13.3	Rare	Chromosomal
Loeys-Dietz syndrome	60,030	38	12.1	Unknown	Monogenic
Left ventricular noncompaction	54,260	29	9.2	Unknown	Monogenic
Turner syndrome	881	24	7.6	Rare	Chromosomal
Brugada syndrome (types 1, 2, and 3)	130	21	6.7	Rare	Monogenic
Familial isolated dilated cardiomyopathy	217,656	20	6.4	Rare	Monogenic
Holt-Oram syndrome	392	18	5.7	Ultrarare	Monogenic
Familial isolated arrhythmogenic right ventricular dysplasia	154	16	5.1	Unknown	Monogenic
Supravalvular aortic stenosis	3,193	14	4.4	Rare	Monogenic
Classical Ehlers-Danlos syndrome	287	11	3.5	Rare	Monogenic
Familial thoracic aortic aneurysm and aortic dissection	91,387	11	3.5	Ultrarare	Monogenic
Heterotaxia (visceral heterotaxy)	450	9	2.9	Rare	Monogenic
Neurofibromatosis type 1	636	9	2.9	Rare	Monogenic
Andersen-Tawil syndrome	37,553	8	2.5	Unknown	Monogenic
Tuberous sclerosis complex	805	8	2.5	Rare	Monogenic
Congenital contractural arachnodactyly	115	6	1.9	Unknown	Monogenic
Jervell and Lange-Nielsen syndrome	768	6	1.9	Ultrarare	Monogenic
Vascular Ehlers-Danlos syndrome	286	6	1.9	Ultrarare	Monogenic
Hypermobile Ehlers-Danlos syndrome	285	5	1.6	Rare	Monogenic
Klippel-Feil syndrome	2,345	5	1.6	Ultrarare	Monogenic
CHARGE syndrome	138	4	1.3	Rare	Monogenic
Lown-Ganong-Levine syndrome	844	4	1.3	Ultrarare	Monogenic
Wolf-Hirschhorn syndrome	280	4	1.3	Rare	Chromosomal
Cardiofaciocutaneous syndrome	1,340	3	1	Unknown	Monogenic
Coffin-Lowry syndrome	192	3	1	Ultrarare	Monogenic
Cornelia de Lange syndrome	199	3	1	Ultrarare	Monogenic
Friedreich ataxia	95	3	1	Ultrarare	Monogenic
Hereditary hemorrhagic telangiectasia	774	3	1	Rare	Monogenic
Klippel-Trenaunay syndrome	90,308	3	1	Ultrarare	Monogenic
Sotos syndrome	821	3	1	Rare	Monogenic
Alagille syndrome	52	2	0.6	Ultrarare	Monogenic
Apert syndrome	87	2	0.6	Ultrarare	Monogenic
Crouzon syndrome	207	2	0.6	Ultrarare	Monogenic
Duchenne muscular dystrophy	98,896	2	0.6	Rare	Monogenic
Emery-Dreifuss dystrophy	261	2	0.6	Ultrarare	Monogenic
Frontonasal dysplasia	250	2	0.6	Unknown	Monogenic
Hereditary ATTR amyloidosis	271,861	2	0.6	Unknown	Monogenic
Johanson-Blizzard syndrome	2,315	2	0.6	Ultrarare	Monogenic
Kearns-Sayre syndrome	480	2	0.6	Ultrarare	Monogenic
MASS syndrome	156,532	2	0.6	Unknown	Monogenic
Noonan syndrome with multiple lentigines (LEOPARD)	500	2	0.6	Unknown	Monogenic
Smith-Magenis syndrome	819	2	0.6	Rare	Monogenic
Spondylocostal dysostosis	1,797	2	0.6	Unknown	Monogenic
47,XYY syndrome	8	1	0.3	Rare	Chromosomal
Aarskog-Scott syndrome	915	1	0.3	Rare	Monogenic
Achondroplasia	15	1	0.3	Rare	Monogenic
Acute intermittent porphyria	79,276	1	0.3	Ultrarare	Monogenic
Arterial tortuosity syndrome	3,342	1	0.3	Ultrarare	Monogenic
Autosomal dominant interatrial communication	1,478	1	0.3	Unknown	Monogenic
Autosomal recessive multiple pterygium syndrome	2,990	1	0.3	Ultrarare	Monogenic
Axenfeld-Rieger syndrome	782	1	0.3	Ultrarare	Monogenic
Becker muscular dystrophy	98,895	1	0.3	Ultrarare	Monogenic
Blackfan-Diamond anemia	124	1	0.3	Ultrarare	Monogenic
Carney complex	1,359	1	0.3	Unknown	Monogenic
Catecholaminergic polymorphic ventricular tachycardia	3,286	1	0.3	Rare	Monogenic
Complex chromosomal rearrangement; t(1;3)	263,708	1	0.3	Unknown	Chromosomal
Complex chromosomal rearrangement; t(14;22)	263,708	1	0.3	Unknown	Chromosomal
Complex chromosomal rearrangement; t(7;12)	263,708	1	0.3	Unknown	Chromosomal
Complex chromosomal rearrangement; t(8;18)	263,708	1	0.3	Unknown	Chromosomal
Congenital heart block	60,041	1	0.3	Unknown	Monogenic
Costello syndrome	3,071	1	0.3	Ultrarare	Monogenic
Distal trisomy 18q	1,716	1	0.3	Unknown	Chromosomal
Distal trisomy 6p	1,745	1	0.3	Ultrarare	Chromosomal
Ellis Van Creveld syndrome	289	1	0.3	Unknown	Monogenic
Fabry disease	324	1	0.3	Rare	Monogenic
Familial atrial fibrillation	334	1	0.3	Unknown	Monogenic
Familial dilated cardiomyopathy with conduction defect due to LMNA mutation	300,751	1	0.3	Unknown	Monogenic
Fragile X syndrome	908	1	0.3	Rare	Monogenic
Incontinentia pigmenti	464	1	0.3	Ultrarare	Monogenic
Kabuki syndrome	2,322	1	0.3	Rare	Monogenic
Kallmann syndrome-heart disease syndrome	2,326	1	0.3	Ultrarare	Monogenic
Kyphoscoliotic Ehlers-Danlos syndrome	536,545	1	0.3	Unknown	Monogenic
Larsen syndrome	503	1	0.3	Ultrarare	Monogenic
McCune Albright syndrome	562	1	0.3	Ultrarare	Monogenic
Meckel syndrome	564	1	0.3	Rare	Monogenic
Mosaic trisomy 8	96,061	1	0.3	Unknown	Chromosomal
Mucopolysaccharidosis type 2 (Hunter)	580	1	0.3	Ultrarare	Monogenic
Mucopolysaccharidosis type 6 (Maroteaux-Lamy)	583	1	0.3	Ultrarare	Monogenic
Muenke syndrome	53,271	1	0.3	Rare	Monogenic
Multiminicore myopathy	598	1	0.3	Unknown	Monogenic
Oculopharyngeal muscular dystrophy	270	1	0.3	Ultrarare	Monogenic
Opitz GBBB syndrome	2,745	1	0.3	Ultrarare	Monogenic
Partial duplication of the long arm of chromosome 13; t(13;14)	262,932	1	0.3	Unknown	Chromosomal
Partial duplication of the long arm of chromosome 13; t(13;15)	262,932	1	0.3	Unknown	Chromosomal
Partial duplication of the short arm of chromosome 11	262,785	1	0.3	Unknown	Chromosomal
Pfeiffer syndrome	710	1	0.3	Unknown	Monogenic
Pseudopseudohypoparathyroidism	79,445	1	0.3	Unknown	Monogenic
Robinow syndrome	97,360	1	0.3	Unknown	Monogenic
Rubinstein-Taybi syndrome	783	1	0.3	Ultrarare	Monogenic
Seckel syndrome	808	1	0.3	Ultrarare	Monogenic
Short QT syndrome	51,083	1	0.3	Unknown	Monogenic
Shprintzen-Goldberg syndrome	2,462	1	0.3	Ultrarare	Monogenic
Steinert myotonic dystrophy	273	1	0.3	Rare	Monogenic
Stickler syndrome	828	1	0.3	Rare	Monogenic
TARP syndrome	2,886	1	0.3	Ultrarare	Monogenic
Tel Hashomer camptodactyly syndrome	3,292	1	0.3	Ultrarare	Monogenic
Tetrasomy 12p (Pallister-Killian syndrome)	884	1	0.3	Rare	Chromosomal
Trisomy X	3,375	1	0.3	Rare	Chromosomal
TTR-related cardiac amyloidosis	85,451	1	0.3	Unknown	Monogenic
Van den Ende-Gupta syndrome	2,460	1	0.3	Ultrarare	Monogenic
CHARGE = coloboma, heart defects, atresia of the choanae, retardation of growth and development, genital abnormalities, and ear abnormalities. ATTR = transthyretin-related amyloidosis. MASS = mitral valve, aorta, skeletal, and skin. LMNA = lamin. GBBB = first letter from the last names of the families that was first diagnosed. TARP = talipes equinovarus, atrial septal defect, robin sequence, and persistence of left superior vena cava. TTR = transthyretin. * According to the diseases prevalences in Orphanet;2 rare (< 1/2,000 - > 1/50,000), ultrarare (≤ 1/50,000 - < 1/1’000,000), and unknown prevalence.