No CrossRef data available.
Article contents
Complex congenital cardiac disease in a patient with partial trisomy for the long arms of chromosomes 11 and 22
Published online by Cambridge University Press: 24 May 2005
Abstract
Abnormalities of chromosomes 11 and 22 are associated with congenital cardiac disease and/or various syndromes. We present a patient with partial trisomy for the long arms of chromosomes 11 and 22, the result of a maternal balanced reciprocal translocation between these two chromosomes. Our patient was dysmorphic and had coarctation of the aorta, an atrioventricular septal defect with common atrioventricular junction and exclusively atrial shunting, patency of the arterial duct, supracardiac totally anomalous pulmonary venous connection, a single kidney, and tracheobronchomalacia. This patient is unusual in having extensive left-sided cardiac involvement, a feature not usually found in this condition.
Information
- Type
- Brief Report
- Information
- Copyright
- © 2003 Cambridge University Press
Abnormalities of chromosome 11 and chromosome 22 may cause congenital cardiac disease, especially in the setting of various syndromes.1–3 We present a patient with trisomy for portions of the long arms of chromosomes 11 and 22 who was dysmorphic and had unusual cardiac malformations involving predominantly the left side of the heart, along with a single kidney and tracheobronchomalacia. To the best of our knowledge, these features have not previously been documented in this syndrome.
Case report
Our male patient was born at 36 weeks of gestation by normal vaginal delivery. He was small for gestational age, weighing 2.26 kg. Dysmorphic features were noted, including a bulbar nose, a right preauricular pit, bitemporal narrowing with slight hypertelorism, a small mouth, and hypoplastic toenails. The parents were healthy and unrelated, with another child who had not had any problems. At birth, the Apgar score was nine at both one and five minutes. He then sustained a cyanotic spell within one hour of age that responded to bagging. He was therefore transferred to the Special Care Baby Unit.
An echocardiogram showed coarctation of the aorta, an atrioventricular septal defect with common atrioventricular junction, separate valvar orifices for the right and left ventricles, and exclusively atrial shunting. The arterial duct was patent, and there was supracardiac totally anomalous pulmonary venous connection. The pulmonary veins drained to a confluence behind the left atrium and communicated with the brachiocephalic vein by means of an ascending vein (Fig. 1). He was also found to have a single kidney and tracheobronchomalacia. Genetic studies showed that the child had partial trisomy for the long arms of chromosomes 11 and 22: 47, XY + der(22)t (11;22)(q23.3;q11.2). Study of the parents revealed that the father had a normal karyotype, while the mother had balanced reciprocal translocation between the long arms of chromosome 11 and 22 at break points q23.3 and q11.2 respectively: 46XX,t(11;22) (q23.3;q11.2).
Figure 1. Top left panel: four chamber view showing the atriums, with an interatrial defect across the oval fossa (large arrow), and a further communication across the atrioventricular septal defect (small arrow). The top right panel, in the same view, shows left-to-right flow across both defects. The second panel on the left shows the ascending vein arising from a confluence behind the atriums, and the second right panel shows the vein rising up to join the brachiocephalic vein. The third panel on the left shows the ascending vein entering a very dilated brachiocephalic vein, while the third panel on the right shows the junction of the dilated brachiocephalic vein with a similarly dilated superior caval vein. The fourth panel, on left and right, seen in four chamber view, shows severe regurgitation across the right atrioventricular valve with significant pulmonary hypertension, while the fifth panels show severe left atrioventricular valvar regurgitation. LA: left atrium; RA: right atrium; Ao: aorta; BV: brachiocephalic vein.
At 22 days of age, he was transferred to a tertiary centre for repair of the coarctation and ligation of the duct. He failed to thrive, and grew along the 0.4th centile. At just over 2 months of age, he was retransferred and underwent patch repair of the septal defects and repair of the totally anomalous pulmonary venous connection. Two weeks later, he also underwent aortic ballooning for recoarctation. Postoperatively, there was severe regurgitation across the left atrioventricular valve. He continued to fail to thrive, remaining in heart failure and in pulmonary hypertension due to the atrioventricular valvar regurgitation. At 8 months of age, he was again submitted to surgery, when a 16 mm Carbomedics valve was inserted in supraannular position. Postoperatively, bilateral diaphragmatic paralysis was noted, requiring bilateral diaphragmatic plication, along with tracheostomy for long term ventilation.
He remained in heart failure despite medication and failed to thrive. Serial echocardiography showed good function of the prosthetic left atrioventricular valve, but with reduced left ventricular function. He also sustained several episodes of narrow complex tachycardia that were controlled with amiodarone. Repeated attempts at extubation failed, after several days at most, because of recurrent infections of the lower respiratory tract. He died at the age of one year and four months of age from septicaemia. The maternal side of the family is being screened.
Discussion
Balanced translocation between the long arms of chromosomes 11 and 22 is not uncommon, and is usually written as t(11;22)(q23.3 q11.2). It appears that only one type of unbalanced translocation is found among the offspring of carriers: 47,XX or XY+der (22)t(11;22)(q23.3;q11.2). This was the pattern found in our patient. The recurrence risk for such an unbalanced translocation is estimated at 2%.2 The phenotypic features of our patient are similar to those described in the literature in this condition.2
Chromosome 11 is critical in formation of the heart and kidneys. Both trisomy and deletion of different portions of this chromosome may cause cardiac malformations with or without associated syndromes. For example, deletion of the long arm at 11q23 may cause Jacobsen syndrome, characterised by dysmorphic features, anemia, thrombocytopenia, hypotonia, failure to thrive, and presence of multiple cardiac defects.4
Cardiac malformations associated with deletions of 11q include Ebstein's malformation,5 isomerism sequence,6 and hypoplasia of the left heart.7 Monosomy for 11q is also associated with congenital cardiac defects.8
Trisomy for 11q is associated not only with congenital cardiac disease, such as septal defects,9 but also with the Robin malformation sequence,1 which was not present in our patient. The area 11q23.3 appears especially critical for formation of the left side of the heart. Indeed, even balanced translocation involving this region may cause hypoplasia of the left heart.10 Chromosome 22 is also important in cardiac and renal development. For example, the Cat-Eye syndrome is associated with anomalous pulmonary venous return and tetralogy of Fallot.3 Although the long arm of chromosome 11 is associated with left-sided cardiac problems, this is not usually the case in the condition described here with partial trisomy. Our patient is unusual, therefore, in having extensive left-sided cardiac involvement.
References
Wallerstein R, Desposito F, Aviv H, Schenk M, Wallerstein DF. Partial trisomy 11q in a female infant with Robin sequence and congenital heart disease. Cleft Palate Craniofac J 1992; 29: 77–79.Google Scholar
Iselius L, Lindsten J, Aurias A, et al. The 11q;22q translocation: a collaborative study of 20 new cases and analysis of 110 families. Hum Genet 1983; 64: 343–355.Google Scholar
Freedom RM, Gerald PS. Congenital cardiac disease and the “cat eye” syndrome. Am J Dis Child 1973; 126: 16–18.Google Scholar
Clang DR, LaBaere RJ II. Jacobsen syndrome: chromosome deletion at 11q23. J Am Osteopath Assoc 1998; 98: 551–554.Google Scholar
de Lonlay-Debeney P, de Blois MC, Bonnet D, et al. Ebstein anomaly associated with rearrangements of chromosomal region 11q. Am J Med Genet 1998; 80: 157–159.Google Scholar
Iida A, Emi M, Matsuoka R, et al. Identification of a gene disrupted by inv(11)(q13.5;q25) in a patient with left–right axis malformation. Hum Genet 2000; 106: 277–287.Google Scholar
Phillips HM, Renforth GL, Spalluto C, et al. Narrowing the critical region within 11q24-qter for hypoplastic left heart and identification of a candidate gene, JAM3, expressed during cardiogenesis. Genomics 2002; 79: 475–478.Google Scholar
Hustinx R, Verloes A, Grattagliano B, et al. Monosomy 11q: report of two familial cases and review of the literature. Am J Med Genet 1993; 47: 312–317.Google Scholar
Menendez I, Rivera H, Morales E, Juan J, Jimenez M. 11q distal trisomy due to a familial 11;18 translocation. Bol Med Hosp Infant Mex 1990; 47: 792–794.Google Scholar
Guenthard J, Buehler E, Jaeggi E, Wyler F. Possible genes for left heart formation on 11q23.3. Ann Genet 1994; 37: 143–146.Google Scholar
Top left panel: four chamber view showing the atriums, with an interatrial defect across the oval fossa (large arrow), and a further communication across the atrioventricular septal defect (small arrow). The top right panel, in the same view, shows left-to-right flow across both defects. The second panel on the left shows the ascending vein arising from a confluence behind the atriums, and the second right panel shows the vein rising up to join the brachiocephalic vein. The third panel on the left shows the ascending vein entering a very dilated brachiocephalic vein, while the third panel on the right shows the junction of the dilated brachiocephalic vein with a similarly dilated superior caval vein. The fourth panel, on left and right, seen in four chamber view, shows severe regurgitation across the right atrioventricular valve with significant pulmonary hypertension, while the fifth panels show severe left atrioventricular valvar regurgitation. LA: left atrium; RA: right atrium; Ao: aorta; BV: brachiocephalic vein.
You have
Access
- 1
- Cited by