Correlation Between Down’s Syndrome and Malformations of Pediatric Surgical Interest

By Antonio Aquino, Marcello Dbmini, Carlo Rossi, Luigi Sardella, Giandomenico Palka, and Pierluigi Lelli Chiesa Pescara, Italy

furpose:This is a collaborative study carried out by Pediatric formations prevailing. The largest number of DS babies Surgeons of the “G.D’Annunzio” University and the Regional were born from mothers under 30 years of age; this is Association of Down Children of Abruzzo (Italy). attributed to the largest birth rate and the least preven-

Methods: Data were collected of malformations combined with Down Syndrome (DS) during a IO-year period in a population of defined age to look for a possible improvement of the patients’ life conditions. Reportedly, 50% of these patients may reach an age of about 60 years.

Results: One hundred twenty-seven DS subjects from this region were evaluated, 54% of whom had associated malformations (13% cardiac, 41% extracardiac, and 13% both). Seventeen patients of 53 underwent surgery for extracardiac malformations, with gastrointestinal mal-

tion at this age. Mothers older than 38 years gave birth to DS babies with the lowest rate of associated malforma- tions.

Conclusion: The role of the pediatric surgeon in multidisci- plinary assistance for DS patients is stressed. J Pediatr Surg 33:1380-1382. Copyright o 1998 by W.B. Saunders Company.

INDEX WORDS: Down’s Syndrome, malformations, epidemi- ology.

D OWN’S SYNDROME (DS) is characterized on a genetic level by the presence of an extra chromo-

some 21 that causes a biological imbalance featuring various degrees of mental, physical, and psychomotor retardation. There is a high incidence of cases: 1 child of 600 to 700 live births. Therefore, it can be considered as the most common human malformative syndrome.’

About 92% of subjects suffer from a simple trisomy of chromosome 21 (47 chromosomes). These patients usu- ally are children of either elderly women or women with long intervals between pregnancies. This form is not inherited.

Trunslocation (46 chromosomes) affects about 5% of patients. One half of the cases feature this aberration sporadically, whereas the other half inherit it. Because this alteration can be inherited, it is always recommended that parents undergo a cytogenetic analysis.

The remaining 3% of patients are affected by mosa- icism (46147 chromosomes). In this case, the flaw takes place at a postzygotic level: two lines of cells are formed, a 46-chromosome line and a 47-chromosome line with an extra chromosome 2 1.

The general risk of having a second DS baby is 2%; in case of inherited translocation the risk is 10% to 15%, and

From Cattedra di Chirurgia Pediatrica and the Istituto di Genetica Medica, UniversitL? “G.D’Annunzio”di Pescara, Italy.

Address reprint requests to Marcello Dbmini, MD, Via S. Domenico II, 40124 Bologna, Italy.

Copyright 0 I998 by WB. Saunders Company 0022-3468/98/3309-OOI2$03.00/0

it grows to 50% for pregnant women with DS (it is widely known that DS women can be fertile).

As far as women aged over 37 are concerned, prenatal diagnosis is based on examining fetal karyotype on the amniotic fluid between the 16th and 18th week of pregnancy. In younger women, it is possible to identify the ones most at risk by checking the level of alpha- fetoprotein, chorionic gonadotrophin, and free estriol in maternal serum (triple-marker test).2

Life expectancy for DS patients has considerably increased in the last years: about 20% die within the first 10 years of life, but 50% can live up to 60 years of age.3

Having acknowledged various congenital malforma- tions in DS patients, a multidisciplinary collaboration is particularly needed. Surgery plays an important and precise role because it helps significantly improve the living conditions of people with DS and sometimes can even save their lives.

Malformations of surgical interest are various and can concern different organs. Given the variety of these malformations, they need to be treated by specifically competent people. Hence, they are usually divided into cardiac malformations and extracardiac malformations.

Cardiac malformations occur frequently (40% to 60% of cases) and require cardiosurgical treatment. The best approach for treatment is to combine a deep knowledge of congenital cardiopathies generally featured in DS children with a nondiscriminating attitude. Although surgery cannot correct the chromosomal anomaly, the improvement, or sometimes even the normalization, of

1380 Journal of Pediatric Surgery, Vol33, No 9 (September), 1998: pp 1380-1382

DOWN’S SYNDROME AND MALFORMATIONS 1381

the cardiac function “. . . will allow to apply the optimal physiotherapy and psychotherapy, resulting in a global amelioration.“4

This last point is very important considering that “( 1) all congenital cardiopathies featured in children with DS can successfully receive surgical treatment and (2) DS does not increase the surgical risk.“4

Extracardiac malformations are to be handled by the pediatric surgeon.

MATERIALS AND METHODS

Analyzing the situation of the Abruzzo region, the data we collected show that in 1993 the number of live births was 12,321, with a total populatron of 1,274,X59.5 In the same period, a census carried out in Abruzzo showed that DS occurred m 489. for a prevalence of 0.04% in the final total population5

Furthermore, because the rate of DS incidence m Abmzzo is 14.47 per 10,000 live births-according to a study carried out in the entire national territory to calculate the total DS incidence from 1978 to 1987-the number of DS subjects born in 1993 in Abruzzo should be 18. This figure is not far from the regional average defined over the last decade, and therefore the number of DS subjects born during that decade should be about 180.

Our study has been carried out over 10 years on a sample of 127 DS subjects, all coming from Abmzzo and aged between 0 and 18 years.

RESULTS

The following statistics were calculated: there were 80 boys (63%) and 47 girls (37%); 69 cases (54%) featured malformations associated with DS; 33 of these patients (26% of the total) suffered from cardiac malformations; 16 of them (13% of the total) suffered from isolated cardiac malformations; 53 cases (4 1%) featured extracar- disc malformations, 17 of them (13.4% of the total) underwent surgical operations (Table 1). Pathological data and treatment are displayed in detail and according to the apparatuses concerned in Tables 2 and 3. Addition- ally there are a number of malformations associated with DS that are generally classified as functional faults and that do not need surgical treatment.

DISCUSSION

It is evident that malformations concerning the gastro- enteric apparatus in people with DS are extremely frequent, particularly stenosal or atresic lesions. It is quite common to find duodenal stenosis or atresias (2.4%) whereas esophageal atresia (0.8%) and anorectal malfor-

Table 1. DS Patients With Associated Anomalies

Total DS with no other anomalies

DS and Isolated cardiac malformations DS and isolated extracardlac malformations

DS and both cardiac and extracardiac malformations

69/I 27 54%

58 46% 16 36

17 i

54%

DS patients with extracardiac malformations

(isolated or not) operated on 17153 32%

Table 2. Cardiac Malformations

NO Operated On

IVD 19 5 IAD 8 -

AVC 7 2

Fallot 2 1

Others 3 1 Total 39 9

NOTE. We observed 33 patients (26%) afflicted by 39 cardiac

malformations. There was one death in a patient operated on for AVC. Abbreviations: IVD. interventricular defect; IAD, interatrial defect;

AVC, atrioventricular channel.

mations (0.8%) are less frequent. Moreover, the large number of references in literature makes it clear that Hirschsprung’s disease associated with DS is not just accidental (Table 3).6

The high percentage of umbilical hernias (11.8%) and rectal diastasis (5.5%) is easily understandable consider- ing that the abdomen in DS patients tends to come forward because of a hypotony of the abdominal muscles giving in to distension (Table 3).

In the genitourinary system, there is a high incidence of “glanular groove” (ie, a blind-ending groove on the glans penis), which is something never before mentioned in literature (Table 3); we found 14 cases, a percentage of 17%. Among other pathological data, it is interesting to note that hemangiomas and pectus excavatum affected 3.9% and 3.1% of our subjects, respectively (Table 3).

Considering our data and the results, one noteworthy fact is the relationship between the faulty chromosomal distribution leading to DS and maternal age. It is well known that a DS subject is more likely to be born to older mothers as demonstrated by the following statistics, calculating the frequency of DS cases per age groups: mothers between 15 and 29, 1: 1,500; mothers between 30 and 34, 1:800; mothers between 35 and 39, 1:270; mothers between 40 and 44, 1: 100; and mothers over 45, 1:50.

Figure 1 summarizes our experience. DS subjects are divided according to maternal age groups. Moreover, the table displays also the percentage of subjects suffering from malformations associated with DS, divided accord- ing to the same maternal age groups. In regard to the percentage of DS babies born, our data are the same as the general data (obviously, mothers younger than 30 years give birth to a percentage of 44.16% DS babies because they are the age group with the most live births and the least prevention; (Fig 1A).7 However, our data concerning the percentage of DS subjects suffering from malformations are very important. It is easily noticed that the highest percentage (63.63%) refers to the age group 30 to 34 years, followed by the age group 35 to 37 years

1382

Table 3. Malformations and Functional Diseases Associated With DS

Observed in the Abruzzo Casuistry

No. of NO No. Not CEISFS Operated Operated

(%) On On

Gastroenteric apparatus Duodenal atresia or stenosis

Hiatal hernia Esophageal atresia

Anorectal malformations Hirschsprung’s disease

Hepatic neoplasm

Cholelithiasis Total

Genitourinary system

Glanular groove Retractil testis Undescended testis

Phimosls

Hypospadias VesicoUreteral reflux

Hypertrophic clitoris Total

Abdominal wall and inguinal canal Umbilical hernia

Rectal diastasis

Hydrocele Epigastric hernia

lnguinal hernia Total

Others

Hemangiomas Pectus excavatum Palatoschisis

Syndactilia

Hydrocephalus Total

Functional diseases

Gastroesophageal reflux Encopresis

Enuresis

Small left colon syndrome

3 (2.4) 2 (1.6)

1 (0.8)

110.8) 1 (0.8)

1 (0.8)

1 (0.8) 10

3

2 1

1 1

1

9

1

1

2

1

1

2

2

1

1 4

1

1

14 (17)

11 (13.8) 5 (6.2)

4 (5) 3 (3.8) l(O.8)

1 (0.8) 39

14 11

4

3 3 1

1

37

15 (11.8)

7 (5.5)

2 (1.6) 1 (0.8)

1 (0.8) 26

14

7 2

1

24

5 (3.9)

4 (3.1) 1 (0.8)

1 (0.8)

1 (0.8) 12

3 4

1

8

17 (13.4) 17 17 (13.4) 17

1 (0.8J 1

1 (0.8) 1

NOTE. Seventeen patients underwent the surgery. Some of the others are waiting for it. The pathologies included in the functional

diseases group were not surgical tie, functional GER, encopresis, enuresis, small left colon syndrome), once excluded anatomic or organic disorders.

with 62.5% and the less than 30 group with 58.5%, whereas the age group greater than 38 years features a considerably lower percentage (37.93%; Fig 1B).

AQUINO ET AL

A -z 30 yrs 3034 yrs 35-37 yrs > 38 yr?,

mother’s age

70%

60%

50%

40%

30%

20%

10%

WA - .”

6 < 30 yrs 30-34yrs 3537yrs > 30 yrs

Fig 1. (A) The percentage of all DS babies related to the age of the mothers. (B) The rate of DS children with associated malformations correlated with the same maternal group. It is interesting to note as in our series, mothers older than 38 years gave birth to DS babies with the lowest rate of associated malformations.

These further epidemiological data cannot be com- pared to anything featured in the literature and could be used to estimate the impact of malformations associated with DS on the population in the future. Furthermore, through particularly careful studies, these data could help find the causes of these malformations and help develop prevention skills.

The pediatric surgeon should be able to make an accurate diagnosis and promptly start a therapy for the various congenital malformations on the basis of a thorough knowledge of them. The pediatric surgeon plays an extremely important role in the multidisciplinary collaboration needed to ensure the best possible assis- tance to people affected by DS.

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2. Liguori G, Lonardo F, Mele E: Progressi nell’assistenza prenatale e neonatale: Lo screenmg blochirmco per la Sindrome di Down ed i difetti de1 tubo neurale (Tri-test). Biol It:l, 1996

3. Mikkelsen M. Paulsen H, Nielsen KG: Incidence, survival and mortality in Down syndrome in Denmark. Am J Med Genet 7:75-78,199O

4. CE.PI.M.: Aspetti epidemiologici, genetici, clinic]. riabllitativl e

sociali della Sindrome di Down. Atti de1 V Convegno “Un future per i bimbi Down.” Genova. l-2-3 dicembre, 1983

5. ISTAT: Annuari StatIstiche Demografiche. 1993 6. Quinn FMJ, Surana R, Puri P: The influence of trisomy 21 on

outcome in children with Hirschsprung’s disease. J Pediatr Surg 29:781-783, 1994

7. Johnson 2, LiIJis D. Delany V, et al: The epidemiology of Down syndrome m four counties in Ireland 1981-1990. 5 Public Health Med 18:78-86,1996