Congenital heart disease and chromossomopathies detected by the karyotype

Scientific articles were searched in MEDLINE database, using the descriptors "karyotype" OR "chromosomal" OR "chromosome" AND "heart defects, congenital". The research was limited to articles published in English from 1980 on.

DATA SYNTHESIS:

Congenital heart disease is characterized by an etiologically heterogeneous and not well understood group of lesions. Several researchers have evaluated the presence of chromosomal abnormalities detected by the karyotype in patients with congenital heart disease. However, most of the articles were retrospective studies developed in Europe and only some of the studied patients had a karyotype exam. In this review, only one study was conducted in Latin America, in Brazil. It is known that chromosomal abnormalities are frequent, being present in about one in every ten patients with congenital heart disease. Among the karyotype alterations in these patients, the most important is the trisomy 21 (Down syndrome). These patients often have associated extra-cardiac malformations, with a higher risk of morbidity and mortality, which makes heart surgery even more risky.

CONCLUSIONS:

Despite all the progress made in recent decades in the field of cytogenetic, the karyotype remains an essential tool in order to evaluate patients with congenital heart disease. The detailed dysmorphological physical examination is of great importance to indicate the need of a karyotype.

heart defects, congenital; karyotype; Down syndrome; trisomy; chromosome aberrations

Author and year of publication	Ferencz et al (1989)⁽³³⁾	Stoll et al (1989)⁽¹⁹⁾	Pradat (1992)⁽³⁴⁾	Hanna et al (1994)⁽³⁵⁾	Goodship et al (1998)⁽³⁶⁾	Grech e Gatt (1999)⁽³⁷⁾	Meberg et al (2000)⁽³⁸⁾
Design	R	R	R	R	P	R	R
Time period	1981–86	1979–86	1981–86	1974–78	1994–95	1990–94	1982–96
Country	United States	France	Sweden	Northern Ireland	England	Malta	Norway
Total n	2.102	801	1.605	388	207	231	360
n with karyotype	ND	153	ND	ND	173	ND	ND
Age	Until 1 year	ABO, LB and SB	SB and LB until 6 months	Until 7 years	Children	Until 1 year	Until 18 years
Cardiac diagnosis	ECO, CAT, SUR or AUT	ECO, CAT, SUR or AUT	ECO, CAT, SUR or AUT	CAT, SUR or AUT	ND	ECO, CAT, SUR or AUT	ECO, CAT, SUR or AUT
Classification in syndromic (%)	–	–	–	–	–	11	–
Total chromosomal abnormality n (%)	271 (12.9)	72 (9)	202 (13)	12 (3)	21 (12.1)	21 (9)	24 (6.7)
Numeric changes (%)	259 (95.6)	69 (95.8)	ND	ND	19 (90.5)	20 (95.2)	20 (83.3)
+21	ND	ND	ND	ND	15	ND	15
+18	17	15	15	ND	1	1	3
+13	16	7	6	ND	–	–	–
45,X	7	1	ND	ND	2	–	1
Klinefelter Syndrome	–	–	ND	ND	–	–	–
Triploidy	–	–	–	ND	–	–	–
Other	1	46	ND	ND	1	19	1
Structural changes(%)	12 (4.4)	3 (4.2)	ND	ND	2 (9.5)	1 (4.8)	4 (16.7)
del(4p)	ND	1	ND	ND	–	–	2
del(5p)	ND	1	ND	ND	–	–	1
i(21q)	ND	–	ND	ND	–	–	–
Other	ND	1	ND	ND	2	1	1
Author and year of publication	*Roodpeyma et al* (2002)⁽³⁹⁾**	*Calzolari et al* (2003)⁽⁴⁰⁾**	*Harris et al* (2003)⁽¹⁶⁾**	*Rosa et al* (2008)⁽²⁹⁾**	*Dadvand et al* (2009)⁽⁴¹⁾**	*Hartman et al* (2011)⁽⁴²⁾**
Design	R	R	R	P	R	R
Time period	1995–2000	1980–94	1981–92	2005–2006	1985–2003	1994–2005
Country	Iran	Italy	USA, France, Sweden	Brazil	England	USA
Total n	346	1.549	12.932	204	5.715	4.430
n with karyotype	ND	300	ND	204	ND	ND
Age	Until 14 years	SB and NB	SB and LB until 1 year	Until 13 years	ABO, SB and NB	ABO, SB and LB
Cardiac diagnosis	PE, ECO or CAT	ECO, SUR or AUT	ECO, CAT, SUR or AUT	ECO, CAT or SUR	ECO, CAT, SUR or AUT	ND
Classification in syndromic (%)	10	25.8	–	–	–	–
Total chromosomal abnormality n (%)	31 (9)	152 (9.8)	2.334 (18)	29 (14)	665 (11.6)	480 (10.8)
Numeric changes (%)	31 (100)	132 (86.8)	2.151 (92.2)	26 (88.5)	ND	418 (89.2)
+21	30	115	ND	23	365	289
+18	1	11	305	2	80	73
+13	–	6	147	–	32	31
45,X	–	ND	34	–	ND	6
Klinefelter Syndrome	–	ND	7	–	ND	4
Triploidy	–	ND	6	–	ND	1
Other	–	ND	ND	1	ND	14
Structural changes(%)	–	ND	ND	3 (11.5)	ND	62 (10.8)
del(4p)	–	ND	ND	–	ND	1
del(5p)	–	ND	ND	–	ND	–
i(21q)	–	ND	ND	1	ND	2
Other	–	ND	ND	2	ND	59

Syndrome	Chromosome alterations	Incidence at birth	% with heart defects*	Associated heart defects
Down	Trisomy of chromosome 21		40–50	CIV, DSAV, PCA, CIA e TOF
Edwards	Trisomy of chromosome 18	1:3.600–8.500	80–100	CIV, CIA, PCA, CoAo, EP, DVSVD, TOF, doença polivalvular e DSAV
Patau	Trisomy of chromosome 13	1:5.000–12.000	80–100	CIA, CIV, PCA, doença polivalvular e dextrocardia
Ullrich-Turner	Partial or total monosomy of Chromosome X	1:2.000–3.000 (?)	17–60	CoAo, VAB, hipoplasia de VE, PVM e EA
Mosaic trisomy of chromosome 9	Mosaicism for chromosome 9 trisomy	±30 cases described	60	CIA, CIV, PCA, DVSVD e persistência VCSE
Triploidy	Triploidy	?	50	CIV, PCA e CIA
Wolf-Hirschorn	Partial deficiency of 4p	1:50.000	30–60	CIA, CIV e EP
Cri-du-chat (cat's cry)	Partial deficiency of 5p	1:50.000	10–55	CIV, CIA, PCA e TOF
Deletion 8p	Partial deficiency of 8p	±40 cases described	65–75	CIV, EP, CIA e TGA
Deletion 9p	Partial deficiency of 9p	±100 cases described	30–65	CIV, PCA e EP
Jacobsen	Partial deficiency of 11q	±75 cases described	65	CIV, Ventrículo único, hipoplasia de VE e CIA
Duplication11q	Partial duplication of 11q	?	60	Variável
Cat-eye syndrome	Tetrasomy or partial trisomy in chromosome 2222	1:50.000–150.000	30–40	Persistência VCSE, DVAPT, TOF, CIV, AT e ausência de VCI
Pallister-Killian	Mosaic tetrasomy for the short arm in chromosome 12	?	25	CIV, EA, PCA e cardiomiopatia hipertrófica
Deletion 22q11.2	Deletion 22q11.2	1:2.000	75–100	TOF, IAA do tipo B, TA, CIV, AP, EP e arco aórtico à direita

Cardiac Malformation	Associated risk (%)	Cromossome abnormality
Tetralogy of Fallot	6–10	+21
	10–15	+13; +18
	10–19	deletion 22q11
Tetralogy of Fallot with pulmonary atresia	26	deletion 22q11
Interrupted aortic arch	25–50	deletion 22q11
Truncus arteriosus	40	deletion 22q11
Tetralogy of Fallot with absent pulmonary valve	>60	deletion 22q11
Double outlet right ventricle	5	+13; +18
Coarctation of aorta	10	Turner Syndrome
Atrioventricular septal defect (complete or partial)	>50	+21; +13; +18
Pulmonary atresia with interventricular communcation	22	deletion 22q11
Pulmonary atresia with ventricular septal defect and major aortopulmonary communicating arteries	35	deletion 22q11
Interventricular communcation outlet	20	+21
Perimembranosa IVC	20	+21; +18
Doubly-committed interventricular communication	20	deletion 22q11

Cardiac malformation	Significantly associated bandings (p<0.05/p<0.01)	Highlty significant assocaitions (p<0.001)
Patent ductus arteriosis	4q32, 6p25-23, 9q31	–
Interatrial comunication	4p13, 4p16, 10p12-11, 12q15	–
Interventricular comunication	1q42-44, 3q24-25, 4q31-34, 11q23-25	4q31, 22q11
Atrioventricular septal defect	6q15-21, 6q23, 8p23, 16q13-22	–
Pulmonary stenosis	7q31, 8p23, 17p13	20p13-11, 22q11
Hipoplastic left heart	–	11q23-25
Aortic stenosis	3p14-11	11q23-24
Truncus arteriosus	2q22-23, 11q23	2q22, 22q11
Tetralogy of Fallot	8p22-21, 22q11	–
Coarctation of aorta	4q31-32, 5q23-31	–

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