trisomy 13 (patau syndrome) and congenital heart defects

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RESEARCH LETTER

Trisomy 13 (Patau Syndrome) andCongenital Heart Defects
Janaina B. Polli,1 Daniela de P. Groff,1 Patrıcia Petry,1 Vinıcius F. Mattos,2 Rosana C. M. Rosa,3
Paulo R. G. Zen,2,3 Carla Graziadio,2,3 Giorgio A. Paskulin,2,3 and Rafael F. M. Rosa2,3,4*1Pediatrics Service, Hospital Materno Infantil Presidente Vargas (HMIPV), Porto Alegre, RS, Brazil2Clinical Genetics, Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA) and Complexo Hospitalar Santa Casa de PortoAlegre (CHSCPA), Porto Alegre, RS, Brazil3Graduate Program in Pathology, UFCSPA, Porto Alegre, RS, Brazil4Clinical Genetics, HMIPV, Porto Alegre, RS, Brazil

Manuscript Received: 1 January 2013; Manuscript Accepted: 17 July 2013

How to Cite this Article:Polli JB, Groff DdP, Petry P, Mattos VF,

Rosa RCM, Zen PRG, Graziadio C,

Paskulin GA, Rosa RFM. 2014. Trisomy 13

(Patau Syndrome) and Congenital Heart

Defects.

Am J Med Genet Part A 164A:272–275.

�Correspondence to:

Rafael Fabiano Machado Rosa, M.D., PhD., Genetica Clınica, UFCSPA/

CHSCPA, Rua Sarmento Leite, 245/403, CEP: 90050-170, Porto Alegre,

RS, Brazil.

E-mail: [email protected]

Article first published online in Wiley Online Library

(wileyonlinelibrary.com): 8 November 2013

DOI 10.1002/ajmg.a.36193

TO THE EDITOR:

Trisomy 13, or Patau syndrome (PS) is considered the third most

common trisomy of autosomal chromosomes, and its prevalence at

birth has been estimated at 1:20,000–29,000 [Wyllie et al., 1994].

Since its first description by Patau et al. [1960] several anomalies,

involving many organs and systems, has been described. We know

that PS is a usually recognizable condition characterized by

multiple congenital anomalies and a poor prognosis [Carey, 2010].

However, recent studies have been showed a modification of

the characteristics of the birth and survival of these patients

[Bruns, 2011]. Congenital heart defects stand out within the

spectrum of abnormalities described [Carey, 2010]. Thus, our

objective was to assess the cardiologic findings of a sample of

patients with PS evaluated in a Clinical Genetics Service of a

pediatric referral hospital in southern Brazil.

The study included patients diagnosed with PS consecutively

evaluated between 1990 and 2012. Their clinical data and the results

of the cytogenetic analysis were obtained from medical records,

emphasizing the cardiac findings. These included gender; age of the

patients at the time of initial evaluation; results of cardiac evalua-

tion, echocardiography, and cardiac surgery; results of the karyo-

type and survival. The Center for Health Information (NIS), an

agency of the State Health Secretary of State of Rio Grande do Sul,

was consulted for obtain the data of death. Heart defects were

described according to the anatomical type verified through echo-

cardiography and divided as complex or not. We also classified

themaccording to the classification suggested byBotto et al. [2001].

Fisher exact test was used for comparison of the frequencies. For

survival analysis, we used log-rank test. Results of P< 0.05 were

considered as statistically significant. This study was approved by

the Research Ethics Committee of the Hospital.

The total sample consisted of 23 individuals and 13 were male.

Theage atfirst evaluation ranged from1 to85days,with amedianof

5 days and an average of 19 days. All patients underwent examina-

tion through karyotype, with 16 cases (70%) with full trisomy of

chromosome 13, 2 (9%) translocations involving chromosomes 13

and 5 (21%) mosaicism.

2013 Wiley Periodicals, Inc.

Twenty-one patients underwent cardiac evaluation (two were

not evaluated because they died early, in the first days of life). Of

these, 14 had an abnormal cardiac evaluation. Among them, 13

underwent echocardiography. The results showed that 12 patients

presented a congenital heart disease. The patient who did not

undergo echocardiography showed description of amorphological

fetal ultrasound with asymmetry of cardiac chambers, suggesting a

possible heart defect. Of the seven patients with normal cardiac

evaluation, six underwent echocardiography and three had a heart

defect.

In total, 19 patients underwent echocardiography, and in 15

cases (79%) a heart defect was verified. Moreover, cardiac defects

were observed in 65% of the total sample. Heart malformations of

these 15 individuals are described in details in Tables I and II. The

main anatomical defects observed were atrial septal defect (53%),

patent ductus arteriosus (37%) and ventricular septal defect (26%).

Cor triatriatum was verified in one patient (5%). From the 15

patients with heart defects, six (37.5%) had a complex defect.

272

TABLE I. Heart Defects Observed in the Sample of Patients with Patau Syndrome in Comparison with the Literature

Present study

Wyllie et al.

[1994]

Sugayama et al.

[1999]

Lin et al.,

[2007]

Maeda et al.

[2011]

Sample size (N) 19 14 20 22 27

Cardiac findings % % % % %

Normal 21 14 44 ND 15

Abnormal 79 86 56 ND 85

Atrial septal defect (53) (21) (24) (50) (19)

Patent ductus arteriosus (37) — (52) (68) —

Ventricular septal defect (26) (64) (33) (50) (15)

Dextrocardia (16) — — — —

Pulmonary atresia (11) — — (18) —

Pulmonic stenosis (5) (7) (ND) (�15) —

Tetralogy of Fallot (5) (7) (ND) (23) (7)

Cor triatriatum (5) — — — —

Double outlet right ventricle — (7) — (�15) (11)

Atrioventricular septal defect — (7) — — (7)

Left atrial isomerism — (7) — — —

Coarctation of the aorta — — — (�15) (7)

Hypoplastic left heart — — — — (4)

Interruption of aortic arch — — — — (7)

Persistent truncus arteriosus — — — — (4)

Total anomalous pulmonary venous return — — — (�15) —

Persistent left superior vena cava — — — (32) —

Interrupted inferior vena cava — — — (�15) —

Hypoplasia of the pulmonary artery — — — (�15) —

Aortic regurgitation — — — (�15) (4)

Tricuspid valve regurgitation — — — (18) —

POLLI ET AL. 273

According to the classificationofBotto et al. [2001], themain group

of abnormalities observed was of the septal defects (46%). Hetero-

taxia and right obstructive defects were both verified in 20% of the

patients. The only case who underwent surgery was a patient with

full trisomy of chromosome 13 presenting pulmonary atresia. The

TABLE II. Heart Defects Verified in the Sample

Patient Sex

Age at first

evaluation (days)

Botto

Group

1 M 9 Heterotaxia

2 F 50 Heterotaxia

3 M 1 Heterotaxia

4 M 60 Outflow tract defects

5 F 2 Right obstructive defects

6 M 3 Right obstructive defects

7 M 4 Right obstructive defects

8 F 27 Septal defects


10 M 3 Septal defects





15 M 21 Patent ductus arteriosus

M, male; F, female; ?, unknown.

surgical procedure was performed at 6 days of life. PS was only

diagnosed after surgery.

From the 19 patients with echocardiographic study, we obtained

survival data of 13. From them, 12 presented a heart defect. The

median of survival of these patients was 26.5 days. The survival of

Classified According to Botto et al. [2001]

et al. [2001]

Surgery

Age of

death (days)Defect type

Heterotaxia � ?

Heterotaxia � 26

Heterotaxia � 9

Tetralogy of fallot � 279

Pulmonary atresia, intact septum � ?

Pulmonary atresia, intact septum þ 8

Pulmonic stenosis � ?

Ventricular septal defect � 3,315 (still alive)

Ventricular septal defect � 3,072 (still alive)

Ventricular septal defect � 12

Atrial septal defect � 26




Patent ductus arteriosus � 37

274 AMERICAN JOURNAL OF MEDICAL GENETICS PART A

the patient without heart defect was 20 days. This patient presented

a mosaicism. We did not observe difference among the survival of

patients with and without septal defects (P¼ 0.3800) and with and

without complex defects (P¼ 0.5568). The only patient who un-

derwent heart surgery died at 8 days of life.

In our literature review, searching articles of English, Spanish,

andPortuguese languages inside the SciELO, LILACS, andPubMed

databases, we found only four studies of patient series with PS after

themiddle of the 1990s describing in detail the cardiac features. The

samples size ranged from 14 to 27 patients and we studied 19

patients. Our study was also the second performed in Latin Amer-

ica. The only study developed in Latin America (and in Brazil)

belongs to Sugayama et al. [1999]. However, it is not indexed in

international databases such as PubMed (Table I).Thefrequencyofcongenitalheartdefectsdescribedinmostof the

studies was similar to ours (79%) and ranged from56 to 86% [Baty

et al., 1994; Wyllie et al., 1994; Sugayama et al., 1999; Maeda

et al., 2011] (Table I). Differences were observed in relation to

the study developed by Rasmussen et al. [2003], who found a

frequency of 45.7% (P¼ 0.0181). In similarity, Pont et al. [2006]

also verified a frequency of 34.8%. The authors pointed several

reasons for these low frequencies, but it is noteworthy the fact that

both studies used selected codes for a limited number of heart

conditions in their methods. Thus, as the own Rasmussen et al.

[2003] pointed, studies including a broader list of heart

defects would possibly find higher frequencies. The studies devel-

oped in the literature evaluated the patients in vivo through

echocardiography [Wyllie et al., 1994; Sugayama et al., 1999; Lin

et al., 2007].Atrial septal defect was the main anatomical abnormality ob-

served in our sample (53%). Its frequency was very variable among

the studies, ranging from19 to 50%.Our frequencywas very similar

to Lin et al. [2007] (50%). Patent ductus arteriosus was also a

common finding observed between 52 and 68% of the cases and in

our study this frequency was 37%. Other common heart malfor-

mation was the ventricular septal defect.We found the lowest value

described (26%). The most similar frequency was also described in

Brazil, in the study of Sugayama et al. [1999] (33%).Dextrocardia, a laterality defect characterized by the position of

the heart at right in the thorax [Stevenson and Hall, 2006], was

observed only in our study. The frequency of pulmonary atresia

found in our sample (11%) was similar to that described in the

literature (8%) [Lin et al., 2007]. Pulmonary stenosis and tetralogy

of Fallot were also described byWyllie et al. [1994], Lin et al. [2007],

and Maeda et al. [2011]. We did not find reports of cortriatriatum

among patients with PS in the literature, even in case reports. The

classic form of this heart defect, as observed in our case, is

characterized by an accessory chamber which joins the left atrium

directly and receives the pulmonary veins with egress through the

opening in the “membrane” [Stevenson and Hall, 2006]. Other

heart defects described among the others studies and not present in

our sample can be seen in Table I. McMahon et al. [2005] and

Yukifumi et al. [2011] also independently described two patients

with a left ventricular noncompaction cardiomiopathy, an unusual

entity. Lin and colleagues [2007] were the only to describe associ-

ated defects as valvular anomalies. The main additional associated

features described consisted of persistence of left upper cava vein

and tricuspide regurgitation (Table I).

Among the heart defects verified in PS, the septal type stands out.

According to Botto et al. [2001], we observed that 46% of the

patients of our sample presented with this kind of heart defect,

which is in accordance with the literature (Tables I and II). One

patient (7%) had an outlet heart defect (a patient with tetralogy of

Fallot).

In our review of the literature, we did not find studies

evaluating whether patients with PS and different types of heart

defects presented with different survival rates. Despite the small

number of patients in our sample, we did not observe differences

in the survival time between patients with and without septal

defects and with and without complex defects. Both of the

patients with survival times of over 8 years presented with heart

defects, ventricular septal defects. One of them was described in

detail by Zen et al. [2008]. Interestingly, ventricular septal defect

was also the main heart defect described by Bruns [2011] among

long-term survivors with full trisomy 13. They verified a frequen-

cy of 61.5%. Both patients with longer survival were still alive.

One was 9 years 1 month of age and the other was 8 years 5

months of age. The first presented with full trisomy of chromo-

some 13 and the second with mosaicism. None of them under-

went heart surgery.

Only one patient of the sample underwent heart surgery. It is

noteworthyhowever, the fact that despite the surgical procedure, he

died at an earlier age (8 days) than the median of the sample (26.5

days). According to Graham et al. [2004], most patients with PS

survive palliative and corrective heart surgeries. Kaneko et al.

[2008] demonstrated an improvement of survival in their series

of patients with pharmacological intervention for ductal patency

and cardiac surgery. However, there is still limited data in the

literature to evaluate the true impact of the heart surgery on the

survival of patients with PS [Graham et al., 2004; Maeda et al.,

2011].

Thus, congenital heart defects are frequent among patients with

PS and echocardiography should be offered to all individuals, even

to those without cardiac symptoms. The common group of defects

observed among them are septal. Some studies point to associated

alterations as valvular abnormalities. Some patients may present

with complex heart defects, but these do not seem to affect their

survival. The survival time also does not seem to be different

between patients with and without septal defects. However,

longitudinal studies are necessary to track cardiac conditions in

individuals with PS.

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