From the Departments of Pediatrics (FG, ES, ED) and Ophthalmology (FMM, HIA), Gülhane Military Medical Academy & Medical School, Ankara, Turkey; and the Center for Molecular Medicine (WB), Cologne Institute of Human Genetics, University of Cologne, Cologne, Germany.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Erkan Sari, MD, Department of Pediatrics, Gülhane Military Medical Academy & Medical School, 06018 Ankara, Turkey.
Aplasia of the lacrimal and salivary glands, as suggested by its name, is characterized by the lack of lacrimal and salivary glands. However, extraglandular manifestations may occur. Because of the complexity of this condition, it can be difficult to diagnose, and patients must be examined thoroughly.1 Alacrima can cause xerophthalmia, red eye, irritability, corneal perforation, and blindness. Aplasia or hypoplasia of the major salivary glands can cause xerostomia, increasing the risk of dental erosion and dental caries. Other complications include periodontal disease, oral soft tissue inflammation, and disorders of chewing and swallowing. Clinicians should monitor the symptoms closely, and should be aware of probable complications.2 According to Wiedemann’s report,1 upslanting palpebral fissures, synophrys, hemangiomas, clinodactyly of the fifth fingers, and shawl scrotum abnormalities are associated with this disorder. This report describes a patient with well-established characteristic findings of aplasia of the lacrimal and salivary glands with the additional findings of growth and development retardation. This association has not been described previously.
A 3-year-old boy, the first child of nonconsanguineous parents, was admitted to the pediatric out-patient clinic of the authors’ institution with mouth dryness, absence of tears even with hard crying, and corneal opacity in the right eye. The patient was born at term by cesarean section after an uneventful pregnancy. Birth weight was 2,750 g, and perinatal hypoxia or anoxia was not reported. Psychomotor development was delayed during infancy, and the patient had a history of recurrent corneal erosions and ulceration in the right eye. Corneal epithelial debridement had been performed twice in another clinic, once at 12 months of age and again at 18 months of age. Physical examination showed short stature (less than the third percentile), normal head circumference, and low weight (less than the third percentile). The oral mucosa was dry; scant amounts of saliva and severe dental caries in multiple teeth were detected. No other family member with similar signs and symptoms has been detected in the patient’s pedigree.
On ophthalmic examination, the eyelids, eyelid margins, and puncta were normal, as were eyelid and eye movements. The patient’s fixation preference was for the left eye, and fixation and following of the right eye was weak. Central corneal stromal opacity, covering the pupil, was present in the right eye on slit-lamp examination (Fig. 1). The anterior chamber was quiet. Findings on funduscopic examination of the right eye were normal. Findings on biomicroscopic and funduscopic examination of the left eye were completely normal.
Figure 1. Central Corneal Stromal Opacity in the Right Eye.
Hemogram, renal function, serum electrolytes, transaminases, blood pH, and blood gases were evaluated, and all findings were within the normal range for the patient’s age. Results of metabolic screening, including thyroid function tests, blood amino acids, lactate, pyruvate, and urinary organic acids, showed no abnormality. Although visual and auditory function had been assessed and considered normal, the patient had delayed speech compared with his peers and the result of the Denver test for developmental delay was positive.
Absence of the minor and major salivary glands was detected with buccal mucosal biopsy and scintigraphy. Bilateral flat feet were detected on orthopedic examination. The karyotype in peripheral blood lymphocytes was normal (46,XY). No mutation in fibroblast growth factor 10 was detected. Multiplex ligation-dependent probe amplification analysis was performed to quantitatively test for deletions and duplications of single exons, and results were normal. Because it was necessary to distinguish between aplasia of the lacrimal and salivary glands and lacrimoauriculodentodigital syndrome, the three LADD genes were analyzed and no mutation was detected.
Findings on magnetic resonance imaging of the brain were normal; however, magnetic resonance imaging of the orbits showed absence of lacrimal glands on both sides (Fig. 2). On Schirmer’s test performed under general anesthesia, there was less than 1 mm of wetting in both eyes at 5 minutes. The patient was diagnosed as having congenital aplasia of minor salivary glands and alacrima associated with growth and development retardation. Frequent administration of artificial tears and polymer gels was ordered. The parents were informed about their child’s disease, and the patient was evaluated at 3-month intervals.
Figure 2. Axial and Coronal T1-Weighted Magnetic Resonance Images of Both Orbits Showing Aplasia of the Lacrimal Glands.
At 4 years of age, the patient was admitted to the ophthalmology department with redness and photophobia in the right eye. Ophthalmic examination showed corneal perforation in the center of central corneal opacification, a collapsed anterior chamber, and hypopyon in the right eye (Fig. 3). Findings on slit-lamp examination of the left eye were completely normal. A therapeutic soft contact lens (PureVision; Bausch & Lomb, Rochester, NY) was used, with frequent administration of artificial tears and use of topical antibiotic eyedrops four times daily. The hypopyon disappeared within 3 days, and the corneal perforation self-sealed completely within 10 days. However, dense corneal scarring developed. During the ensuing 15 months of follow-up, with frequent application of artificial tears and polymer gel, no recurrence of corneal erosion or perforation was observed.
Figure 3. Corneal Perforation with Hypopyon and a Collapsed Anterior Chamber.
Absence or hypoplasia of the major salivary glands may be seen with or without absence of lacrimal glands and nasolacrimal ducts and puncta. This entity is a complex, pleiotropic autosomal dominant disorder and may show a difference in phenotypic expression. The incidence and mutation rate are unknown. This situation may cause xerostomia, periodontal disease, and dental caries. Canalization of the lacrimal and salivary ducts occurs at the eighth week of gestation, and an abnormality at this stage is believed to be responsible for the pathogenesis of this anomaly. Ramsey3 first described familial absence of salivary glands in a father and daughter in 1924, and Blackmar4 described congenital absence of the lacrimal puncta with aptyalism, decreased lacrimation, and severe dental caries in a boy in 1925. Ferreira et al.2 described a Brazilian family in which several members were affected and had different clinical features.
Reported cases of congenital absence or hypoplasia of salivary glands suggest that the condition is autosomal dominant and is associated with several abnormalities. According to Wiedemann’s report,1 upslanting palpebral fissures, synophrys, hemangiomas, clinodactyly of the fifth fingers, and shawl scrotum abnormalities are associated with this disorder. In the current case, aplasia of the lacrimal and salivary glands was accompanied by growth and development retardation. However, the etiologic cause of growth retardation could not be found.
Congenital absence of the salivary glands is often regarded as part of certain syndromes, such as lacrimoauriculodentodigital syndrome and mandibulofacial dysostosis. Lacrimoauriculodentodigital syndrome, also known as Levy–Hollister syndrome, is characterized by pronounced dysplasia in various organ systems. The resulting disturbances primarily affect the lacrimal glands, the inner and outer ear, the salivary glands, and the osseous framework.5 These disorders must be excluded in patients with absent salivary glands.
Alacrima can cause significant ocular morbidity because persistent dryness of the ocular surface can be difficult to manage. Lifelong tear supplementation may be necessary, but particular attention should be paid to preservatives and concomitant hypersensitivity. These eyes are at high risk for corneal erosions, ulcers, and infections.6 Besides continuous tear supplementation, appropriate treatment with antibiotics may be necessary to control microbial infection. If corneal perforation occurs, prompt treatment to restore the anterior chamber is important to maintain ocular integrity. Therapeutic soft contact lenses are effective for small corneal perforations, as in the current case.7 Also, use of prophylactic topical antibiotics with therapeutic soft contact lens application in the current case resulted in successful closure of the corneal perforation. However, the long-term prognosis for visual rehabilitation may be poor in patients with alacrima because of persistent dry eye, which would preclude future keratoplasty. In addition, central corneal opacities may result in sensory deprivation amblyopia.
Aplasia of the lacrimal and salivary glands is a rare genetic disorder. This report describes a case of aplasia of the lacrimal and salivary glands with the unusual additional findings of growth and development retardation.
- Wiedemann HR. Salivary gland disorders and heredity. Am J Med Genet. 1997;68:222–224. doi:10.1002/(SICI)1096-8628(19970120)68:2<222::AID-AJMG20>3.0.CO;2-V [CrossRef]
- Ferreira AP, Gomez RS, Castro WH, Calixto NS, Silva RA, Aguiar MJ. Congenital absence of lacrimal puncta and salivary glands: report of a Brazilian family and review. Am J Med Genet. 2000;94:32–34. doi:10.1002/1096-8628(20000904)94:1<32::AID-AJMG7>3.0.CO;2-F [CrossRef]
- Ramsey WR. A case of hereditary absence of the salivary glands. Am J Dis Child. 1924;28:440.
- Blackmar FB. Congenital atresia of all lacrimal puncta with absence of salivary glands. Am J Ophtalmol. 1925;8:139–140.
- Lehotay M, Kunkel M, Wehrbein H. Lacrimo-auriculo-dentodigital syndrome: case report, review of the literature and clinical spectrum. J Orofac Orthop. 2004;65:425–432.
- Arya SK, Chaudhuri Z, Jain R, Nahar R, Sood S. Congenital alacrima in Pierre Robin sequence. Cornea. 2004;23:632–634. doi:10.1097/01.ico.0000121700.74077.31 [CrossRef]
- Yoshita T, Kobayashi A, Sugiyama K. Bilateral corneal perforation in an infant with congenital alacrima. J Pediatr Ophthalmol Strabismus. 2006;43:236–238.