Case Series

RMMJ Rambam Maimonides Medical Journal Rambam Health Care Campus 2024 January; 15(1): e0005. ISSN: 2076-9172
Published online 2024 January 19. doi: 10.5041/RMMJ.10519

Familial Occurrence of Isolated Late-onset Nasolacrimal Duct Obstruction in Two Unrelated Families

Anat Bahat Dinur, M.D., M.P.H.,#1* Ortal Buchbut, M.D.,#2* Libe Gradstein, M.D.,2 Baker Elsana, M.D.,2 Ofek Freund, B.Sc.,3 Ohad S. Birk, M.D., Ph.D.,3,4 and Erez Tsumi, M.D., M.H.A.2

1Department of Otolaryngology & Head and Neck Surgery, Soroka University Medical Center and Clalit Health Services, The Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel
2Department of Ophthalmology, Soroka University Medical Center and Clalit Health Services, The Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel
3The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev, Beer-Sheva, Israel
4Genetics Institute, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Corresponding author.
#Contributed equally.

To whom correspondence should be addressed. E-mail:
*These authors contributed equally to this work.


Late-onset nasolacrimal duct obstruction (NLDO) as a result of inflammatory processes causing dacryo-stenosis is a common entity affecting mostly women. While a few mechanisms have been suggested as contributors to the expression of NLDO, the trigger for the inflammation remains mostly unknown. Familial predilection for this condition has not been previously reported. We present two families with multiple individuals affected with congenital or late-onset NLDO, describe the signs and symptoms of the affected individuals, and explore their medical history for any contributing factors. Family A, spanning four generations, included 7 female patients affected by late-onset NLDO. Family B, spanning two generations, included 8 individuals affected by either congenital or late-onset NLDO. This case series suggests a familial predisposition to NLDO, apparently with an autosomal dominant inheritance pattern. Further studies are needed to elucidate the molecular basis of this genetic predisposition.

Keywords: Endo-DCR, epiphora, nasolacrimal duct obstruction, oculoplastic


Nasolacrimal duct obstruction (NLDO) is associated with epiphora and recurrent dacryocystitis and usu-ally requires surgical intervention. The congenital form (CNLDO) is caused by incomplete perinatal perforation of the membrane present at the nasolac-rimal duct opening. Late-onset disease is thought to be associated with obstruction along the nasolacrimal duct and is subdivided into primary and secondary acquired nasolacrimal duct obstruction (PANDO and SANDO, respectively).1 Primary acquired NLDO is caused by inflammation and fibrosis of the naso-lacrimal system without any known precipitating cause, although anatomical and hormonal predis-posing factors have been suggested.26 The smaller bony diameter of the lacrimal duct or reduced ex-pression of estrogen receptors in lacrimal mucosa is more pronounced in women than in men, contrib-uting to the higher incidence of PANDO in females. Of all the non-traumatic forms of dacryostenosis, PANDO accounts for most of the cases observed in adults. The secondary form is diagnosed when the patient’s history indicates likely causes such as trauma, sinus disease, sinus surgery, or systemic dis-eases.1 The exact incidence of late-onset NLDO is not known, although it is considered quite common.7

Familial occurrence of CNLDO has been reported previously. In most of these cases, CNLDO occurred as part of a systemic syndrome or was associated with various developmental anomalies. Little is known regarding the inheritance pattern of isolated CNLDO. Several studies have suggested familial occurrence of isolated CNLDO with an autosomal dominant pedigree pattern, but the genetic basis has not been identified.8 Only one germline mutation associated with CNLDO has been reported to date. Foster et al. identified a homozygous IGSF3 muta-tion in a consanguineous family with CNLDO.9

To the best of our knowledge, there have been no reports of familial occurrence of late-onset NLDO. Here we report two large unrelated Israeli Jewish families of Moroccan and Ashkenazi ancestry with several members affected by isolated late-onset NLDO. In one of the families, both CNLDO and late-onset NLDO were found. We describe the clinical features of the disease in these two families.


Several patients from two unrelated families of Israeli Jewish ancestry presented to the oculoplastic clinic in the ophthalmology department at Soroka University Medical Center (SUMC), Beer-Sheva, Israel, with similar complaints of epiphora. Their pedigrees were obtained, and they underwent com-plete ophthalmic examination. General medical his-tory was reviewed, and systemic symptoms and signs were recorded. Clinical data, including demograph-ics, clinical presentation, systemic and ocular dis-orders, and treatment were collected for all affected individuals. The diagnosis of PANDO and CNLDO was made by history and physical examination, as well as by Jones tests, when needed. Study of this case series was approved by SUMC Institutional Review Board and Ethics Committee and adhered to the tenets of the Declaration of Helsinki.

Family A
Family A included 7 female patients with late-onset NLDO spanning four generations (Figure 1). This non-consanguineous family was of Moroccan Jewish ancestry. All females diagnosed with late-onset NLDO were daughters of mothers also affected by the condition. The age of onset ranged from 18 to 40 years, with the presenting sign in all cases being epiphora (Table 1). Most affected individuals had no history of chronic ocular or periocular inflamma-tion, sinus inflammatory disease, or systemic abnor-malities. Most affected individuals had normal find-ings on ophthalmic examination and no sinonasal pathology except NLDO. Blepharitis and cataract were diagnosed in two different subjects; however, these conditions are not known to be associated with NLDO. None of the patients had ptosis, facial dys-morphism, or abnormalities of eye movements. Two subjects had a history of sinusitis, but no correlation was found between sinusitis onset and epiphora exacerbations. Surgical intervention was necessary for NLDO treatment in all but one patient. A com-puted tomography scan of the orbits in one patient revealed normal results, showing no pathological or contributing factors to the obstruction.
Figure 1Figure 1
Family A Pedigree
Table 1Table 1
Family A: Demographics and Medical History of Affected Individuals.

Family B
Family B, of non-consanguineous Ashkenazi ances-try, included 8 affected individuals: 2 female pa-tients in generation II were affected by late-onset NLDO, 1 patient in generation II was affected by CNLDO, and 2 male and 3 female patients in gener-ation III were affected by CNLDO which spontane-ously resolved with age (Figure 2). No predisposing factors to NLDO were noted (Table 2). Among the CNLDO cases, two were confirmed and recorded by a physician, and the other four were reported by parents.
Figure 2Figure 2
Family B Pedigree
Table 2Table 2
Family B: Demographics and Medical History of Affected Individuals.


We report two unrelated extended families with multiple members affected by late-onset NLDO. The absence of associated systemic conditions or local risk factors for NLDO implies a genetic predispose-tion. While familial cases of CNLDO have been traced, to the best of our knowledge, this is the first report of familial occurrence of late onset NLDO.

The incidence of PANDO is greater in women than in men.1 This higher occurrence in females is thought to be the outcome of significantly smaller dimensions of the lower nasolacrimal fossa and mid-dle nasolacrimal duct. Groessl and colleagues noted that changes in the anteroposterior dimensions of the bony nasolacrimal canal coincide with osteo-porotic changes throughout the body.2 Others have suggested menstrual and hormonal fluctuations and augmented immune status as factors that may con-tribute to the disease process.36 These may explain the high prevalence of PANDO in middle-aged and elderly women, when the hormonal changes leading to generalized de-epithelialization in the body may cause the same process within the lacrimal sac and duct.1 It is possible that an anomalous nasolaryngeal duct structure is inherited in an autosomal domi-nant fashion in both sexes, but the already narrow lacrimal fossa in women predisposes them to ob-struction by sloughed-off debris, thereby manifest-ing as overt NLDO only in affected females. The fact that only female family members in Family A were affected with NLDO could also imply a non-Mendelian mode of inheritance. In Family B, how-ever, two male children were affected by CNLDO. Moreover, three CNLDO patients had mothers with no history of NLDO. Therefore, if late-onset NLDO and CNLDO are considered as the same entity, the most likely mode of heredity is autosomal dominant with incomplete penetrance and variable expression.

The occurrence of both late-onset NLDO and CNLDO in Family B could imply that late-onset NLDO might be a form of occult CNLDO that be-comes clinically apparent after puberty. Affected individuals in Family B developed a more severe, congenital disease in the younger generation as opposed to the milder, adult-onset disease in older individuals, which may indicate the mechanism of genetic anticipation. It should be mentioned that while a few studies suggested familial occurrence of congenital dacryocystocele and CNLDO, a clear in-heritance pattern has not been reported, except for the association with a homozygous IGSF3 variation in one consanguineous family with CNLDO.9

In summary, to the best of our knowledge, this is the first report of familial occurrence in two un-related non-consanguineous families of late-onset NLDO, with likely autosomal dominant heredity with incomplete penetrance and variable expression. Further studies are needed to elucidate the molecu-lar basis of this genetic predisposition.


CNLDO congenital nasolacrimal duct obstruction
NLDO nasolacrimal duct obstruction
PANDO primary acquired nasolacrimal duct obstruction
SANDO secondary acquired nasolacrimal duct obstruction.


Conflict of interest: No potential conflict of interest relevant to this article was reported.

Worak, SR.; Bengzon, AU. Nasolacrimal duct obstruction and epiphora. Updated June 16, 2023. Medscape. [(accessed December 6, 2023).]. Available at:
Groessl SA, Sires BS, Lemke BN. An anatomical basis for primary acquired nasolacrimal duct obstruction. Arch Ophthalmol. 1997;115:71–4.
Ali MJ, Schicht M, Paulsen F. Qualitative hormonal profiling of the lacrimal drainage system: potential insights into the etiopathogenesis of primary acquired nasolacrimal duct obstruction. Ophthalmic Plast Reconstr Surg. 2017;33:381–8.
Ohtomo K, Ueta T, Toyama T, Nagahara M. Predisposing factors for primary acquired nasolacrimal duct obstruction. Graefes Arch Clin Exp Ophthalmol. 2013;251:1835–9.
Taban M, Jarullazada I, Mancini R, Hwang C, Goldberg RA. Facial asymmetry and nasal septal deviation in acquired nasolacrimal duct obstruction. Orbit. 2011;30:226–9.
Kashkouli MB, Sadeghipour A, Kaghazkanani R, Bayat A, Pakdel F, Aghai GH. Pathogenesis of primary acquired nasolacrimal duct obstruction. Orbit. 2010;29:11–15.
Woog JJ. The incidence of symptomatic acquired lacrimal outflow obstruction among residents of Olmsted County, Minnesota, 1976–2000 (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2007;105:649–66.
Suh, DW.; Haklmeh, C.; Shahraki, K. Congenital anomalies of the nasolacrimal duct. [(accessed December 6, 2023).]. Updated December 1, 2023 Medscape. Available at:
Foster J 2nd, Kapoor S, Diaz-Hortaa O, et al. Identification of an IGSF3 mutation in a family with congenital nasolacrimal duct obstruction. Clin Genet. 2014;86:589–59.