epiphora

Lacrimal Puncta Agenesis

Clinical Characteristics
Ocular Features: 

Nasolacrimal duct obstruction may occur in 20% of infants.  The blockage is usually located at the Valve of Hasner in the distal intranasal segment of the nasolacrimal drainage system.  In the absence of other anatomic anomalies, the obstruction often spontaneously clears by one year of age.  Recurrent conjunctivitis and epiphora are frequent occurrences.  A dacryocystocele may develop and in the lacrimal sac area and purulent material can often be expressed by applying mild pressure.

However, the literature contains scattered references to rare familial cases with recurrent dacryocystitis in which a dacryocystocele and lacrimal puncta agenesis are present.

Systemic Features: 

Facial cellulitis and respiratory distress may be associated. 

Genetics

Homozygous mutations in the IGSF3 gene (1p13) have been reported in multiple male offspring of a consanguineous couple.  The parents and an unaffected brother were heterozygous for the mutation.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Some patients can benefit from a dacryocystorhinostomy procedure with relief of the epiphora and chronic conjunctivitis. 

References
Article Title: 

Glaucoma, Congenital Primary A

Clinical Characteristics
Ocular Features: 

This may be the most common type of early (infantile, congenital) glaucoma.  Elevated intraocular pressure may be present at birth but sometimes is not evident until the first year of life or in some cases even later.  Irritability, photophobia, and epiphora are early signs.  The globe is often buphthalmic, the cornea is variably cloudy, and breaks in the Descemet membrane (Haab striae) may be present.  Frequently the iris root is inserted anteriorly in the region of the trabecular meshwork.  The anterior chamber often appears abnormally deep.  Early reports of a membrane covering the angle structures have not been confirmed histologically.  The mechanism causing elevated IOP seems to be excessive collagen tissue in the anterior chamber angle that impedes normal aqueous outflow.   The pressure is usually in the range of 25-35 mmHg but this is variable as the course can be intermittent.  It should be considered a bilateral disease although about one-fourth of patients have only unilateral elevations of pressure even though trabecular abnormalities are present.

Optic cupping may begin temporally but the more typical glaucomatous cupping eventually occurs.

Systemic Features: 

No consistent systemic abnormalities are associated with primary congenital glaucoma.  However, it is important to note that glaucoma is a feature of many congenital malformation syndromes and chromosomal aberrations.

Genetics

Congenital glaucoma of this type can result from both homozygous (25%) and compound heterozygous mutations (56%) in the CYP1B1 gene on chromosome 2 (2p22-p21) which codes for cytochrome P4501B1.

Evidence from many sources suggests that congenital glaucoma of this type is an autosomal recessive disorder. Parental consanguinity is common, the segregation ratio is approximately 25%, and the occurrence of congenital glaucoma among all offspring of two affected parents can be cited as support for this mode of inheritance.  Many cases occur sporadically but this is consistent with expectations in small human sibships.  Curiously, though, males are affected more often than females.

Another autosomal recessive infantile (congenital) glaucoma (600975), GLC3 or type B, is caused by mutations in GLC3B located at 1p36.2-p36.1.  A third locus at 14q24.3 has also been proposed  for GLC3, type C.  Autosomal recessive primary congenital glaucoma (so-called) type D (613086) is caused by a mutation in LTBP2 located at 14q24 near the GLC3C locus and heterozygous mutations in TEK are responsible for type E (617272).

Other modes of inheritance have been described and, for now, this form of glaucoma, like others, has to be considered a genetically and clinically heterogeneous disorder pending additional genotyping.  Early onset glaucoma is also a feature of numerous malformation and chromosomal disorders.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Some of the usual glaucoma drugs are ineffective as a result of obstruction to aqueous flow through the trabecular meshwork so that surgical treatment is the therapy of choice in most cases.   Monitoring of axial length has been proposed as helpful in gauging the effectiveness of pressure control.  In some patients the pressure normalizes spontaneously. 

It is important in the evaluation of patients with glaucoma that systemic evaluations be done because of the frequent syndromal associations.

References
Article Title: 

Congenital glaucoma and CYP1B1: an old story revisited

Alsaif HS, Khan AO, Patel N, Alkuraya H, Hashem M, Abdulwahab F, Ibrahim N, Aldahmesh MA, Alkuraya FS. Congenital glaucoma and CYP1B1: an old story revisited. Hum Genet. 2018 Mar 19. doi: 10.1007/s00439-018-1878-z.

PubMed ID: 
29556725
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