A Case of Trisomy 13 Mosaicism With Aortic Root Dilatation.

We present a 6-year-old female child, with prenatal diagnosis of trisomy 13 mosaicism and nondisjunction, a bicuspid aortic valve, and severe aortic root dilatation. This patient is only the third reported case of aortic dilatation in the setting of trisomy 13 mosaicism. (Level of Difficulty: Intermediate.).

History of Presentation

The patient was a 6-year-old girl who presented to the pediatric cardiology clinic for a follow-up cardiac evaluation because of a complex medical and surgical history and aortic root dilatation. The patient was diagnosed with trisomy 13 in utero, with a fetal echo that revealed a small ventricular septal defect (VSD) that closed spontaneously postnatally. She was also found to have a bicuspid aortic valve, dilated aortic root, and mild coarctation of the aorta. There was no aortic stenosis or regurgitation present, and her coarctation never caused any obstruction. Her vital signs on presentation were a heart rate of 85 beats/min, blood pressure of 106/58 mm Hg, and temperature of 36.9 °C. Oxygen saturation was 100% in room air. Her height was 109 cm (second percentile) and weight 17.1 kg (third percentile). She was wheelchair bound and had features of trisomy 13. Cardiac examination showed a regular rate and rhythm without murmur, normal S1 and S2, a systolic click not variable with respiration, no friction rub, or gallop. She was well perfused with 2+ pulses and no clubbing, cyanosis, or edema.

Learning Objectives

To realize that severe aortic dilatation may occur in infants with trisomy 13 mosaicism.

To learn that children with trisomy 13 mosaicism have longer survival.

To understand that children with trisomy 13 mosaicism may not have heart murmur but should have echocardiograms to rule out congenital heart defects.

Past Medical History

Medical history is significant for trisomy 13 mosaicism with mitotic nondisjunction, cleft palate, seizures, umbilical hernia, congenital glaucoma and cataracts, and VSD. Past surgical history includes bilateral cataract extraction and gastrostomy tube placement.

Investigations

Echocardiogram on most recent clinic visit showed a bicuspid aortic valve (left and right cusp fusion), aortic annulus measured at 12 mm, severely dilated aortic root at 30.5 mm (z score: 8.56), sinotubular junction 17 mm, and ascending aorta 15 mm. The aortic arch was not obstructed (Figure 1). There was mild left ventricular apical trabeculation, normal left and right ventricular size and systolic function; there was no mitral valve prolapse. There was trace aortic valve regurgitation but no stenosis. Electrocardiogram revealed normal sinus rhythm with ventricular rate of 78 beats/min, QRS axis 77 °, and normal intervals

Figure 1

2-Dimensional Echocardiogram Depicting the Aortic Valve, Aortic Root, and Aortic Arch

(A) Parasternal long-axis image demonstrating the dilated aortic root. (B) Parasternal short-axis image demonstrating the bicuspid aortic valve. (C) High right parasternal image demonstrating the dilated aortic root and ascending aorta (arrow). (D) Suprasternal sagittal image demonstrating the aortic arch (Arch). Ao = aortic root; BAV = bicuspid aortic valve.

Management

We have followed the child at our pediatric cardiology clinic after she was discharged from the neonate intensive care units. We started her on enalapril 1 mg twice a day when she was 4 years old. Her aortic root measured 28 mm (z score: 7.9); the enalapril dose was adjusted to 1.2 mg twice a day on her most recent follow-up visit based on her weight. She has been also on multiple antiseizure medications, antibiotics, eye ointments, and respiratory therapy agents. Her hemodynamics was normal, but her aortic root was severely dilated.

Discussion

Trisomy 13, also called Patau syndrome, is a clinical syndrome with multiple congenital anomalies including cardiac and cerebral defects, polydactyly, and numerous facial malformations; it occurs in approximately 1 per 5,000 live births. The most common etiology is meiotic nondisjunction, with higher risk in advanced maternal age. However, 20% of trisomy 13 cases can result from unbalanced translocation and, rarely, 5% from mosaicism. Mosaicism is caused by mitotic nondisjunction error that results in 3 copies of chromosome 13 in some cells but 2 copies in others. The prognosis of trisomy 13 is extremely poor, with median survival of 7 to 10 days in live-born patients and a <10% 1-year survival rate. Prognosis is better in cases of mosaicism or unbalanced translocation. Congenital heart defects, associated in 70% of patients with trisomy 13 vary from VSD, atrial septal defect (ASD), tetralogy of Fallot, atrioventricular septal defect, and double-outlet right ventricle, with VSD and ASD being the most common. Bicuspid aortic valve and aortic dilatation are not common in patients with trisomy 13, with it being extremely rare in cases of trisomy 13 mosaicism. To our knowledge, we present only the third reported case of aortic root dilatation in a patient with trisomy 13 mosaicism. Aortic root dilatation is common in other genetic diseases, including Marfan syndrome, Ehlers-Danlos syndrome, and Turner syndrome. The standard treatment for Marfan syndrome includes beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers to decrease the rate of ascending aortic root dilatation, as well as prophylactic aortic surgery.

Most practitioners—61 of 81 (75%)—reported prescribing medications based on aortic size z scores; 78% of this group started medications at a z score from 2 to <5. The remaining 20 (25%) of 81 complete responders reported prescribing medications based on absolute aortic diameter. In a survey of Canadian pediatric cardiologists, 80% reported treating aortic dilatation with medications, with 61% using beta-blockers and 30% prescribing angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors.

Monin et al presented a 19-year-old male patient with trisomy 13 mosaicism in a subset of 15% of cells that presented with aortic root dilatation. The patient presented with a bicuspid aortic valve and severe aortic dilatation that measured 42 mm at sinus of Valsalva at age 16 and 45 mm 7 months later. This case was, at the time, only the second reported case of aortic dilatation in trisomy 13. There was no gene known to be involved in aortic root dilatation located in chromosome 13, but some loci were suggested being involved in bicuspid aortic valve. The patient was managed with a beta-blocker, with surgery proposed upon evolution of pathology.

Mosaicism was also present in the first reported case of aortic dilatation in trisomy 13 mosaicism. Ghawi et al presented a 16-year-old male patient with trisomy 13 mosaicism with no previous cardiac history who had a new murmur, hypertension, and congestive heart failure. The management included initial stabilization on the night of admission with a diuretic and an antihypertensive agent, along with surgical intervention.

Conclusions

Trisomy 13 mosaicism is a rare genetic disease, but it has longer survival compared with Patau syndrome. We recommend early identification of cardiac malformation(s) with echocardiogram. They may not have heart murmur, but they could have severe aortic root dilation. Management of trisomy 13 mosaicism should be tailored to individual needs. Data on medical or surgical management for aortic root dilatation in these patients are limited.

Funding Support and Author Disclosures

This research was supported in part by the Louisiana Board of Regents Endowed Chairs for Eminent Scholars program. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.