Congenital isolated lacrimal gland agenesis is an extremely rare condition. However, it should be kept in mind in the differential diagnosis of dry eyes in children. This condition is occasionally associated with salivary gland agenesis and abnormalities in the lacrimal drainage system, particularly occlusions of the lacrimal punctae and canaliculi.1
Aplasia of the lacrimal and major salivary glands (ALSG) is a rare autosomal dominant disorder that is characterized by aplasia, atresia, or hypoplasia of the lacrimal and salivary glands. It presents with a constellation of symptoms, including irritable and recurrent eye infections, xerostomia, and dental caries that can often be mistaken for Sjögren's syndrome.1
A 5-year-old boy presented to our ophthalmology clinic with his parents, who noticed he had absence of tearing during crying and red eyes. Slit-lamp examination showed decreased tear margin film with normal punctae. Corneal staining showed inferior, superficial punctate epithelial erosions. The rest of the eye examination was normal. A Schirmer test could not be performed due to the patient's young age.
Systemic examination and rheumatology consultation along with purified protein derivative test, chest x-ray, and serum angiotensin-converting enzyme titer were unremarkable. Dental and oral examinations were unremarkable, with normal eruption of primary teeth without evidence of dental caries. There was no family history of similar complaints or abnormal facial morphologic features among the patient's parents or siblings.
Due to the reported cases of agenesis of both lacrimal and salivary glands, orbital and neck magnetic resonance imaging (MRI) was performed with and without intravenous contrast (gadolinium), which revealed the absence of both lacrimal glands (Figure 1). Salivary glands were unremarkable with normal architecture (Figure 2).
(A) Axial T1, (B) axial T2 fat-suppressed, (C) coronal T1 fat-suppressed post-contrast, and (D) coronal T2 fat-suppressed sequences through the orbit demonstrate bilateral absence of lacrimal glands.
(A) Axial and (B) coronal T2 fat-suppressed sequences at the upper neck show normal architecture of both (A) parotid and (B) sub-mandibuler glands.
The treatment options included frequent instillation of artificial tears, temporary and permanent obliteration of the punctae, and tarsorrhaphy. These options were thoroughly discussed with the patient's parents, who preferred the use of artificial tears because the amount of dryness did not cause significant keratopathy. The child was referred back to his treating physician and follow-up reports up to 1 year indicated cure from his complaints and satisfaction with the treatment.
Dry eye is a disorder of the tear film due to tear deficiency or excessive tear evaporation leading to interpalpebral ocular surface damage and symptoms of ocular discomfort. It is less frequent in children than in adults and has several possible causes, including congenital, immune, dermatological, endocrine, environmental, nutritional, and post-infectious conditions. Congenital lacrimal gland agenesis is considered a rare cause of dry eye syndrome in childhood.
Dry eye syndrome is an uncommon diagnosis in children. This disease can be associated with systemic disorders such as Sjögren's syndrome, Riley-Day syndrome, ectodermal dysplasia syndromes, hypovitaminosis (A) due to congenital small bowel atresia, and graft-versus-host disease following bone marrow transplantation.2
The lacrimal gland begins to develop in the lower eyelid at the end of the second month of intrauterine life. Fibroblast growth factor 10 (FGF10) is found to be the inducer for its development.3 Orbital and palpebral parts are formed in the fifth month, but the full differentiation occurs 3 to 4 years after birth. Thus, any disarrangement in early intrauterine life may cause lacrimal gland agenesis.4
The main lacrimal glands produce approximately 95% of the aqueous component of tears, and accessory lacrimal glands of Krause and Wolfring produce the remainder. The secretion of tears has a basic (resting) component secreted by the accessory lacrimal glands and a much greater reflex component secreted by the main lacrimal glands.5
Congenital bilateral lacrimal gland agenesis, particularly in its isolated form, is considered an extremely rare entity in the ophthalmologic literature, with only two previously reported cases (Table 1). Demetriades and Seitzman reported a case of isolated unilateral lacrimal gland agenesis,6 whereas Sahinoglu et al. reported a case of congenital bilateral lacrimal gland agenesis and normal salivary glands on MRI as in our case.4 A male predominance is noted among the cases of isolated lacrimal gland agenesis, which might suggest a genetic background and thus be a target for future genetic testing.
Cases of Isolated Lacrimal Gland Agenesis
Lacrimal gland agenesis can be observed in ALSG, which, in addition to the lacrimal glands, is accompanied by salivary gland agenesis. Genetic studies for ALSG revealed that alteration in the FGF10 gene is the main cause for this disorder.1 If ALSG is accompanied by facial dysmorphisms, outer and inner ear anomalies and hearing loss, teeth anomalies, distal limb malformations, and, more infrequently, impairment of kidney and lung development, then a more severe disorder called Lacrimo-auriculo-dento-digital syndrome (LADD) will result. This is also found to be associated with FGF10 alteration in addition to FGF-Receptor 2 and FGF-Receptor 3 mutations.7
LADD is now thought to be a more severe variant of ALSG, and because FGF10 is the inducer for lacrimal gland development, we hypothesize that isolated lacrimal gland agenesis is a milder variant of the same entity.
Treatment options include frequent instillation of topical lubrication by artificial tears, which is inconvenient for both children and parents. Punctual occlusion is another option that can be temporary with silicon plugs, which is not without complications but has several advantages in such cases because it is less invasive than other surgical options and is reversible. Permanent occlusion with cauterization or surgical procedures should be avoided in young patients because their tear production tends to fluctuate.5
The majority of reports concentrate on aggressive lifelong lubrication in addition to permanent surgical punctual occlusion to prevent severe dry eye syndrome, which can cause xerophthalmia, red eye, irritability, corneal ulcer, perforation, and blindness. Therefore, it is critical to stress to the family the importance of consistent lifelong lubrication therapy.
- Chapman BD, Shashi V, Krise DJ. Case report: aplasia of the lacrimal and major salivary glands (ALSG). Int J Pediatr Otorhinolaryngol. 2009;73:899–901. doi:10.1016/j.ijporl.2009.03.004 [CrossRef]
- Mac Cord Medina F, Silvestre de Castro R, Leite SC, Rocha EM, de Melo Rocha G. Management of dry eye related to systemic diseases in childhood and longterm follow-up. Acta Ophthalmol Scand. 2007;85:739–744. doi:10.1111/j.1600-0420.2007.00934.x [CrossRef]
- Makarenkova HP, Ito M, Govindarajan V, et al. FGF10 is an inducer and Pax6 a competence factor for lacrimal gland development. Development. 2000;127:2563–2572.
- Sahinoglu N, Tuncer S, Alparslan N, Peksayar G. Isolated form of congenital bilateral lacrimal gland agenesis. Indian J Ophthalmol. 2011;59:522–523. doi:10.4103/0301-4738.86333 [CrossRef]
- Kanski JJ. The dry eye. In: Kanski JJ. Clinical Ophthalmology, 5th ed. London: Elsevier Science; 2003:56–61.
- Demetriades A, Seitzman G. Isolated unilateral congenital lacrimal gland agenesis presenting as filamentary keratopathy in a child. Cornea. 2009;28:87–88. doi:10.1097/ICO.0b013e3181814ca9 [CrossRef]
- Shams I, Rohmann E, Eswarakumar VP, et al. Lacrimo-auriculodento-digital syndrome is caused by reduced activity of the fibroblast growth factor 10 (FGF10)-FGF receptor 2 signaling pathway. Mol Cell Biol. 2007;27:6903–6913. doi:10.1128/MCB.00544-07 [CrossRef]
Cases of Isolated Lacrimal Gland Agenesis
|Demetriades & Seitzman,6 2009||6||Male||Unilateral filamentary keratitis||Left isolated lacrimal gland agenesis||Left permanent punctual occlusion|
|Sahinoglu et al.,4 2011||7||Male||Decreased visual acuity, foreign body sensation||Bilateral isolated lacrimal gland agenesis||Bilateral permanent punctual occlusion|
|Current||5||Male||Absent tears on crying, red eye||Bilateral isolated lacrimal gland agenesis||Artificial tears instillation|