Introduction

Down syndrome, caused by trisomy 21, the most common chromosomal anomaly, has been associated with a number of ophthalmic features [1]. The lacrimal drainage system is often affected and the incidence of nasolacrimal duct obstruction is 5–30 % [2–6].

The incidence of lacrimal fistula is approximately one in 2,000 live births. Although systemic diseases are not associated with this abnormality, a few associated disorders have been identified [7–15]. Sullivan et al. reported five cases of lacrimal fistula in Down syndrome patients, and Keseru et al. reported a single case of bilateral lacrimal fistula associated with Down syndrome [11, 14]. Two Down syndrome patients were included in a series of 67 patients with congenital lacrimal fistula in a study by Welham et al. [16]. Satchi et al. reported a case of a Down syndrome patient with a double lacrimal puncta and lacrimal fistula [17].

A review of English literature (PubMed search) showed only nine cases of Down syndrome-associated lacrimal fistula, published in four articles, and only one of nine cases had bilateral lacrimal fistula [11, 14, 16, 17]. In this study, we investigated the prevalence and clinical characteristics of congenital lacrimal fistula in Down syndrome patients.

Materials and methods

The medical records of all Down syndrome patients who were referred to the pediatric ophthalmology clinic of Seoul National University Hospital and Seoul National University Bundang Hospital for ocular evaluation from 2000 to 2010 were retrospectively reviewed to identify patients with congenital lacrimal fistula. The demographic data, clinical features (the presence and laterality of fistula and accompanying adnexal and oculomotor abnormalities including congenital nasolacrimal duct obstruction), the type of surgery performed, and surgical outcome of Down syndrome patients with congenital lacrimal fistula were recorded. The prevalence of congenital lacrimal fistula in Down syndrome patients was calculated upon this data.

Written informed consent was obtained from all patients. The study protocol was reviewed and approved by the Institutional Review Board of Seoul National University Bundang Hospital and was conducted in accordance with the Declaration of Helsinki.

Results

Of 377 Down syndrome patients who visited the pediatrics clinic of Seoul National University Hospital and Seoul National University Bundang Hospital, 198 patients were referred to the ophthalmology clinic for routine ocular examination. Lacrimal fistula was noted in eight (4.04 %) patients, and bilateral lacrimal fistula was noted in four (2.02 %) of these eight patients. Two of these eight patients (25 %) also had lower canalicular obstruction, and seven of these eight patients (87.5 %) had congenital nasolacrimal duct obstruction, which was confirmed by lacrimal probing and lacrimal irrigation intraoperatively or at outpatient clinic. Six of eight patients (75 %) had upper eyelid epiblepharon, four of eight patients (50 %) had lower eyelid epiblepharon, and four of eight patients (50 %) had prominent epicanthal fold. One of these eight patients (12.5 %) had punctal agenesis and two patients (25 %) had exotropia. The cases are summarized in Tables 1 and 2.

Table 1 Case summary of congenital lacrimal fistula in patients with Down syndrome
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Table 2 Adnexal and oculomotor abnormalities in Down syndrome patients with congenital lacrimal fistula
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All patients experienced tearing from their eyes, but not from their lacrimal fistula opening. Six of the eight patients underwent surgical management. Within this cohort of surgically treated patients, five underwent excision of the lacrimal fistula for cosmetic reasons, three also underwent lacrimal silicone intubation for combined nasolacrimal duct obstruction, and one received lacrimal silicone intubation without lacrimal fistula excision. Lacrimal silicone intubation could not be performed for the left eye of case 3, due to upper punctal agenesis and complete nasolacrimal duct obstruction that could not be probed. The patient’s parents refused further surgery such as dacryocystorhinostomy. Among six patients who underwent surgical management, two underwent bilateral upper lids epiblepharon repair and another two patients underwent bilateral upper and lower lids epiblepharon repair. Two of eight patients did not undergo any surgical procedure, because one of them was very young and the parents of the other refused surgical management.

The mean age of the patients at surgery was 54.3 months (range, 14–94 months), and the mean period of postoperative follow-up was 41.8 months (range, 10–124 months). The relatively high mean age of patients at surgery was due to late referral. The lacrimal fistula was well obliterated in all five patients who underwent surgical excision (Fig. 1). Two patients complained of persistent tearing from their eyes after surgical management, and one patient showed upper punctal agenesis and complete obstruction of the nasolacrimal duct that could not be overcome by probing during the surgery. The other patient did not undergo lacrimal silicone intubation because he showed good passage for lacrimal irrigation. However, the patient was diagnosed as bilateral partial nasolacrimal duct obstruction afterward.

Fig. 1
figure 1

A Down syndrome patient diagnosed with bilateral congenital lacrimal fistula and bilateral upper eyelid epiblepharon. (a) Note the bilateral lacrimal fistula and discharge at the fistula opening. (b) The patient underwent surgical excision of the bilateral lacrimal fistula, upper eyelid epiblepharon repair, and z-epicanthoplasty. Six weeks after the surgery, lacrimal fistula was well obliterated

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Discussion

Lacrimal fistula was found in eight (4.04 %) of 198 Down syndrome patients. Four (2.02 %) of these patients showed bilateral lacrimal fistula, and seven (87.5 %) showed accompanying nasolacrimal duct obstruction. The prevalence of lacrimal fistula was remarkably higher in our sample of Down syndrome patients than in the general population (0.05 %) [8]. In our study, four (50 %) of the eight Down syndrome patients had bilateral lacrimal fistula. Although the incidence of bilateral lacrimal fistula in the general population is unknown, Song et al. reported that only one patient had bilateral lacrimal fistula among 14 patients with lacrimal fistula but without Down syndrome [18]. Thus, it is likely that bilateral lacrimal fistula is more frequent in Down syndrome patients than in the general population.

Nasolacrimal duct obstruction was noted in seven (87.5 %) of eight patients with lacrimal fistula and Down syndrome in this study. The prevalence of nasolacrimal duct obstruction in Down syndrome patients with lacrimal fistula (87.5 %) was higher than that of Down syndrome population without lacrimal fistula (5–30 %), and was also higher than that of the general population with lacrimal fistula (27–36 %), even after considering the reported high prevalence of nasolacrimal duct obstruction in Down syndrome patients [2–6, 16, 18].

In most cases, congenital lacrimal fistula is not generally associated with systemic diseases, but it has been reported to be associated with thalassemia, preauricular fistula, hypospadias, a balanced 6p and 13q translocation, CHARGE syndrome, VACTERL, naso-orbital meningocele, ectrodactyly-ectodermal dysplasia-clefting syndrome, or Down syndrome [7, 9–15]. Our cases showed that congenital lacrimal fistula occurs in Down syndrome patients; thus, a careful examination for congenital lacrimal fistula as well as for other well-known ocular disorders should be carried out in these Down syndrome patients.

The incidence of epiblepharon is about 61 % in Asian Down syndrome patients and is much higher than in non-Down syndrome Asian patients [6, 19]. The high incidence of upper eyelid epiblepharon (75 %) and lower eyelid epiblepharon (50 %) in current study is thought to be one of the characteristic ocular findings in Asian patients with Down syndrome. The direct association between epiblepharon and congenital lacrimal fistula could not be proven in this case series.

A prominent epicanthal fold was observed in four (50 %) of the eight patients with lacrimal fistula. The prominent epicanthal fold is a typical finding in Down syndrome (61–96.7 %) [6, 20], and it may conceal fistula openings, because the lacrimal fistula opening is sometimes located within this fold (Fig. 2). The prominent epicanthal fold accompanied by tearing may also cause skin maceration, inflammation, discharge, and cosmetic problems by tears welled up between the opposing skin layers. Therefore, prominent epicanthal folds in all Down syndrome patients should be examined carefully to identify hidden lacrimal fistula openings.

Fig. 2
figure 2

A Down syndrome patient diagnosed with bilateral congenital lacrimal fistula, bilateral upper and lower eyelid epiblepharon, and prominent epicanthal folds. (a) Note that the prominent epicanthal folds are masking the lacrimal fistula opening. (b) Excision of bilateral lacrimal fistula, repair of upper and lower eyelid epiblepharon, and z-epicanthoplasty was performed. Three months after the surgery, lacrimal fistula was well obliterated, and epiblepharons were corrected

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Congenital lacrimal fistula is mostly asymptomatic and tends to be overlooked, but active treatment may be indicated if tearing, inflammation, or cosmetic problems occur by lacrimal fistula, because it can be well obliterated by surgical treatment even in Down syndrome patients. However, even after successful obliteration of fistula, tearing may not be completely resolved owing to concomitant conditions such as nasolacrimal duct obstruction, epiblepharon, or prominent epicanthal fold, because these conditions frequently coexist with congenital lacrimal fistula and can cause not only cosmetic problems but also tearing and skin problems. Thus, these conditions should be evaluated carefully for appropriate management.

This study has a few limitations. First, it may be difficult to draw a meaningful conclusion from eight patients, even though the eight patients are the largest series of congenital lacrimal fistula in Down syndrome to the best of our knowledge. Second, prevalence of congenital lacrimal fistula in Down syndrome patients in current study maybe biased, because approximately only half of the Down syndrome patients from the pediatric clinic were referred to a single ophthalmology clinic and asymptomatic patients with fistula only may not be referred. Third, the high proportion of comorbidity of both congenital lacrimal fistula and nasolacrimal fistula might be overstated; because fistula alone may be asymptomatic and it is possible some lacrimal fistula patients without nasolacrimal duct obstruction were not referred.

In conclusion, the prevalence of lacrimal fistula is higher in Down syndrome patients than in the general population, and the fistula is frequently bilateral in these patients. Down syndrome patients should be thoroughly examined for congenital lacrimal fistula and for nasolacrimal duct obstructions, because those with congenital lacrimal fistula are likely to have accompanying nasolacrimal duct obstruction.