Young adolescent with trisomy 13

Abstract

A young adolescent girl with trisomy 13 was admitted twice to the paediatric department: the first time because of haematocolpos due to uterus didelphys and unilateral transverse vaginal septum, and the second time because of heart failure due to ruptured sinus of Valsalva aneurysm. As a consequence of the historical early high mortality rate in trisomy 13, we are not aware of known complications in older patients. With better survival nowadays through childhood, we advise structural ultrasonographic cardiac and female genital screening in trisomy 13 patients reaching adolescent age.

Background

Our knowledge on trisomy 13, also known as Patau syndrome, has grown since it was first documented in 1960.¹ Most common cause of trisomy 13 is an extra 13th chromosome, the non-disjunction type. In fewer cases, it is caused by a translocation or mosaicism.²

Trisomy 13 is characterised by severe developmental delay and multiple congenital anomalies, cardinally orofacial clefts, microphthalmia/anophthalmia and postaxial polydactyly of hands and/or feet.² In more than 50% of trisomy 13, the following anomalies in specific organs/systems are observed^{3 4}: central nervous system (holoprosencephaly, intellectual disability and deafness), craniofacial appearance (abnormal auricles, microphthalmia/anophthalmia, sloping forehead), skin and limbs (ie, simian crease, hyperconvex narrow fingernails, polydactyly), heart (ventricular septum defect (VSD), patent ductus arteriosis, atrial septal defect (ASD) and dextroposition), renal defects and genitalia (cryptorchidism in males; bicornuate uterus in females).

Autosome 13 is relatively gene-poor, perhaps contributing to their in utero survival.³ Live born trisomy 13 have a high mortality of over 50% in the first week and approximately 6%–12% of these infants will live past 1 year.^{5 6} In these infants, a 5-year survival of 9.7% is seen.⁷ Factors significantly contributing to a better survival are being born at a term gestational age compared with preterm births and being female.⁷

Due to its high mortality, management of the patient with trisomy 13 is primarily based on problems that occur at infant age. With improved prenatal screening and genetic testing combined with a better understanding of the trisomy 13 phenotype, management of a child with trisomy 13 has been enhanced. For example, congenital heart surgery showed over 50% decrease of mortality up to 24 months.⁸ In a descriptive study 9% (total 94 children) survived past 10 years.⁶ So infants with disorders such as trisomy 13 and 18 once deemed lethal are now often living significantly longer, although with a broad range of associated disabilities due to their underlying disease process.^{9 10} In this case, we were confronted with complications of uterus didelphys occurring and heart failure due to ruptured sinus of Valsalva aneurysm (SVA) both in her teens. Goal of this case report is to create awareness of the increased risk of genitourinary and cardiac complications in adolescents with trisomy 13.

Case presentation

A young teenager, known with non-disjunction type trisomy 13, was presented at our emergency department because of abdominal pain and fever since 1 day. Furthermore, she had anuria since 1 day and also minimal menstruation. A medical history included uneventful term birth, agenesis of the corpus callosum, small muscular VSD, central apnea, intellectual disability, recurrent airway tract infections, epilepsy, hearing difficulties, recurrent urinary tract infections with bladder retention and pyelectasis in both kidneys. Physical examination showed a painful, uncooperative girl with a distended and tense abdomen. Her temperature was 38.2°C. Because of a retention bladder and urinary tract infection, ceftabuten was started and a urinary catheter was given. Because of persistent fever and no clinical improvement after 2 days, we switched to intravenous cefuroxime with good effect. Blood culture remained negative.

Pain and fever recurred on day 4. Ultrasound of the abdomen showed a mass in the lower abdomen (figure 1), suggestive of a periappendicular abscess. A percutaneous drain and morphine led to immediate relief of symptoms, surprisingly producing only blood and no pus. CRP remained low (maximum 33 mg/L), but haemoglobin level dropped remarkably from 9.0 to 5.8 g/dL for which a blood transfusion was given. At a second ultrasound of the abdomen the drain appeared to be inserted in an ovary/salpinx without a sign of a (recent) appendicitis as described before. Hydrometrocolpos was suspected, secondarily leading to urinary retention and urinary tract infection. MRI confirmed an uterus didelphys (figure 2) and haematocolpos of the right part (figure 3). Colposcopy showed a transverse vaginal septum with hymen imperforatus of the right part, both successfully resected. Anticonceptive therapy was started to prevent menstruation.

Figure 1.

Ultrasound showing the abdominal mass.

Figure 2.

MRI of lower abdomen showing uterus didelphys.

Figure 3.

Abdominal MRI showing haematocolpos of the right uterus in a sagittal view.

A few year later in her mid-teens, she presented at our emergency department again, this time with fatigue, vomiting and stomach pain since 1 day. Physical and laboratory examination showed no abnormalities, specifically no signs of infection. During the admission for rehydration by nasal-gastric tube, she developed respiratory failure, requiring oxygenation via non-rebreather mask. Physical examination revealed a new-onset heart murmur and diffuse crepitations bilaterally. No other signs of cardiac congestion were found and ECG was normal. PCR for respiratory viruses was negative. Amoxicillin clavulanic acid was started because of possible aspiration pneumonia on chest X-ray. Transthoracic echocardiogram and CT angiography were performed when she developed cardiogenic shock, showing SVA with communication between ascending aorta and right atrium (figure 4). With high-flow nasal canula and low-dose diuretics, breathing and circulation improved. During an angiography, a Konar MF Occluder 8/6 was successfully placed in the wide sinus of Valsalva, bluntly ending in a 5 mm fistula, shunting from right coronary artery to right atrium. Also, lifelong acetylsalicylic acid was started.

Figure 4.

CT-A with frontal view of the heart/thorax showing a fistula at the origo of the right coronary artery. CT-A, CT angiography.

Outcome and follow-up

After the first episode of hospitalisation because of the haematocolpos, she fully recovered after the resection of the imperforated hymen and the transverse vaginal septum, and starting with contraceptive injection to prevent menstruation.

For her second hospitalisation because of the SVA, she was transmitted to a level 3 hospital. Using angiography, the shunting aneurysm was successfully closed followed by quick recovery. Lifelong acetylsalicylic acid is given because of the risk of thrombotic complications due to the contact between the device and the tricuspid valve. She is seen annually by the paediatric cardiologist. In her adolescence, she is currently doing well with a normal exercise tolerance, performing her usual daily activities.

Discussion

Due to the variety of anomalies seen in trisomy 13 and its high neonatal/infant mortality, screening for cardiac and renal anomalies is performed as early as possible after birth, important for subsequent management.^1–3 No standard screening is advised for genital abnormalities although 12% of babies with trisomy 13 (per 100 live births) have structural defects of the genital tracts, for example, duplication and/or anomalous insertion of fallopian tubes, uterine cysts, hypoplastic ovaries, abnormal shaping of the uterus, uterus bicornuate and—as in this case—uterus didelphys.2 3 11–14 Looking at uterus didelphys, 75% of these cases are associated with transverse vaginal septum that can lead to obstruction.¹³ Correct diagnoses was delayed in this case, due to signs of an urinary tract infection and retention bladder, frequently occurring in trisomy 13, and uneventful menarche.

For diagnosing uterus anomalies, a transabdominal ultrasonography is first choice in the preadolescent patient. Transvaginal ultrasonography can be more accurate, but is not recommended in the not sexual active patient. When ultrasonography is not conclusive, due to small size and shape of the uterus at this age, MRI is advised.¹³ MRI has a near 100% accuracy for evaluation of genital developmental anomalies such as uterus didelphys in this case.¹³

Trisomy 13 is also frequently associated with congenital heart diseases (CHD) such as septal defects (ASD, VSD, atrio-VSD), aortic and pulmonary valve anomalies, patent ductus arteriosus and tetralogy of Fallot.^{3 14} Nowadays, more patients with trisomy 13 survive through childhood. Interventional management of CHD in the first months after birth is associated with higher long-term survival, especially in low-risk CHD.¹⁵ Cardiacally corrected patients have a significantly higher 15-year survival than palliative patients.¹⁵

SVA is a rare anomaly, usually arising from the right coronary sinus (76.9%), that occurs due to a weakness in the aortic wall that forms part of the sinus causing dilatation and formation of a blind pocket.^{16 17} Congenital SVA is frequently associated with connective tissue disorders, such as Marfan syndrome.¹⁷ Clinical symptoms depend on direction and degree of rupture and dilation of the SVA, and can vary from asymptomatic to chestpain, dyspnoe and arrhythmia.¹⁶ Ghawi et al reported a patient in adolescence with trisomy 13 and SVA rupture, in whom no cardiac anomalies were found in the neonatal period. SVA is associated with other CHD,^{16 18} most commonly VSD (44.2%) and aortic regurgitation (43.3%).^{16 18 19} Detailed echocardiography is an accurate method for diagnosing SVA.^{16 20 21} Cardiac catheterisation with aortography remains nevertheless the gold standard with MRI and CT as promising alternatives.^{16 20 21} Early diagnosis and intervention are essential for improving prognosis. Actual survival rate is approximately 63% at 10 years with New York Heart Association classifications I or II after surgical repair.¹⁶ Transcatheter closure of ruptured SVA in adult patients reports a short-term success rate of 90%.²²

As cardiac defects such as SVA cannot always be found neonatally, and as its course can be very insidious, such as in our case, it is important to perform cardiac screening in the general long-term follow-up, such as imbedded in Marfan syndrome.²³

Due to its high mortality, a non-interventional approach in trisomy 13 is currently standard of care in the neonatal period and first year of life.^{24 25} Medically indicated interventions should be considered in newborns with trisomy 13, after adequate parental counselling. This includes interventions previously withheld such as positive pressure ventilation and surgical repair of problems such as CHD.¹⁰

After infant age, only little prognostic data are available, based on small descriptive, retrospective studies and case reports.^5–7 Even knowing that less than 10% of the live-born children with trisomy 13 will get past the age of 1 year, parents may ask for therapeutic interventions, as 97% of parents with trisomy 13 children feel they enriched their lives, regardless of life span.⁶ Therefore, a more balanced approach of the (older) patients with trisomy 13 has been suggested regarding personal circumstances and parental autonomy.^{15 26} When these patients reach adolescence, screening according to the trisomy 18 surveillance guideline is advised.⁹ In addition, we recommend standard echographic screening of the heart and genitalia interna in girls in advance of menarche.

In conclusion, ultrasonographic screening of cardiac and female genital abnormalities should be standard of care in children with trisomy 13 reaching adolescence, to prevent unnecessary delay in diagnosing and treating complications.

Learning points.

• Medically indicated interventions should be considered in newborns with trisomy 13, after adequate parental counselling.

• A more balanced approach of the (older) patients with trisomy 13 has been suggested regarding personal circumstances and parental autonomy.

• When these patients reach adolescence, screening according to the trisomy 18 surveillance guideline is advised.

• Ultrasonographic screening of cardiac and female genital abnormalities should be standard of care in children with trisomy 13 reaching adolescence, to prevent unnecessary delay in diagnosing and treating complications.

Ethics statements

Patient consent for publication

Consent obtained from parent(s)/guardian(s).