Glaucoma is a progressive optic neuropathy characterized by a degeneration of the optic nerve, which is usually associated with elevated intraocular pressure. The increase in intraocular pressure is probably caused by a reduction in outflow of aqueous humor through the trabecular outflow pathways. The degeneration of the optic nerve is the result of the loss of individual retinal ganglion cells, where the ganglion cells die by an apoptotic mechanism.
Glaucoma accounts for 15% of blindness worldwide, and is the second leading cause of blindness in the world. It is a heterogeneous group of disorders, the majority of which are associated with an open, normal appearing anterior chamber angle with normal trabecular meshwork and are termed open angle glaucoma. Open angle glaucomas have onset in mid adulthood and relentless slow progression. The juvenile and infantile glaucomas are more severe clinically and more difficult to manage.
Primary congenital glaucoma is a clinical and genetic entity clearly distinct from the juvenile forms. It is an autosomal recessive disorder caused by condition that results from a developmental defect in the trabecular meshwork anterior chamber angle and manifests in the neonatal or infantile period. Classic clinical characteristics include elevated intraocular pressure, enlargement of the globe, particularly the anterior segment, edema and opacification of the cornea, with rupture of Descemet's membrane, thinning of the anterior sclera and atrophy of the iris, anomalously deep anterior chamber, structurally normal posterior segment, except for progressive optic atrophy; and photophobia, blepharospasm, and hyperlacrimation. Primary congenital glaucoma occurs when the developmental anomalies of the angle prevent adequate drainage of aqueous humor, so that the intraocular pressure is elevated. Because the coating of the infantile eye is elastic, it stretches in response to elevated pressure, resulting in buphthalmos.
The prevalence of primary congenital glaucoma varies across ethnic communities and geographical boundaries, ranging from 1 in 10,000-20,000 in the western populations to 1 in 2,500 and 1 in 1,250 in the Saudi Arabian and Gypsy populations of Slovakia, respectively.
Using linkage analysis, the primary congenital glaucoma locus has been mapped to three different loci, GLC3A (at 2p21), GLC3B (at 1p36), and GLC3C (at 14q24.3). Although these three loci have been linked to primary congenital glaucoma, only the gene, CYP1B1 at the GLC3A locus has been identified to date. More than 55 different mutations in the coding region of this gene have been identified in CYP1B1 to be causal for primary congenital glaucoma in different ethnic backgrounds and populations highlighting the allelic heterogeneity of the condition. These include deletion, insertion, point mutation, missense, nonsense, frameshift, and chain terminator mutations. CYP1B1 encodes a dioxin inducible member of subfamily I of the cytochrome p450 protein superfamily and is expressed in tissues of the anterior chamber angle of the eye. The human CYP1B1 gene consists of three exons of which the first is non-coding. The putative open reading frame starts in the second exon and is 1629 base pairs in length. Molecular modeling experiments suggest that mutations observed in primary congenital glaucoma patients interfere with the integrity of the CYP1B1 molecule as well as its ability to adopt a normal conformation and bind heme.
Alfadhli et al. (2006) screened CYP1B1 gene mutations in 17 unrelated Kuwaiti probands with primary congenital glaucoma. All patients had an aggressive form of glaucoma with age on onset within the first year of life. Of the 17 patients, eight (47%) were found to be homozygous and one heterozygous for the G3987A mutation, making it the most common mutation in this population. Sequencing revealed three other mutations, including one novel missense mutation, G7999A, and two previously described mutations, C4645A and G7940A. Alfadhli et al. (2006) also found a novel missense polymorphic change, T8102G (Val422Gly), in homozygous state in two and heterozygous state in one patient and 18 of 210 normal control chromosomes. No genotype-phenotype correlation could be detected in this study.
Levy et al. (2005) analyzed the final outcome of surgery in 25 Arab Bedouin children with primary congenital glaucoma (PCG) presenting within the age of three months. Complete clinical history taking, including family history, clinical features, intraocular pressure (IOP), horizontal corneal diameter, and cup/disc ratio (c/d) were taken. Of the 45 eyes operated upon, 39 eyes (86.5%) were successfully surgically corrected. Levy et al. (2005) observed that the type of operation performed, gender, consanguinity, or age at first operation did not have any relation to the success rate. Cases with no family history showed a better rate of success, whereas eyes with initial high IOP and c/d ratio were at a higher risk for failure. In fact, in multivariate analysis, initial IOP was found to be the only independent predictive factor for surgical failure.
Al-Zahrani (2002) reported a 5 and half year-old Saudi girl, born to first-degree consanguineous parents, who presented at birth with severe bilateral congenital glaucoma and ambiguous genitalia. At the age of five years she lost vision in her left eye, and received anti-glaucoma treatment for her right eye. She and had three other affected members in the family. Her 14-year-old brother had severe bilateral congenital glaucoma and lostvision in both eyes. In addition, her 10 and a half-year-old sister had ambiguous genitalia with large clitoris, no palpable gonads, and labioscrotal fusion. One of her first cousins had died at 4-months of age had ambiguous genitalia as well.
Khan et al. (2011) described two siblings of a consanguineous Saudi parent. Both siblings, brother and sister, were diagnosed to have glaucoma at the age of 9 and 10 years respectively. Both experienced difficulties in distance vision which warranted medical intervention. Past medical history for both siblings was unremarkable. On examination, they had increased intraocular pressure along with characteristic optic disk cupping, and a defect in the visual field was also noticed. Ophthalmologic examination was performed for all family members. Goldmann visual fields in subsequent visits were consistent with glaucoma. Both siblings started on timolol, 0.5% twice daily on both eyes. Opthalmologic screening for the parents and their healthy child showed normal visual acuity and intraocular pressure. Khan et al. (2011) identified underlying genetic defects in the CYP1B gene.
Khan et al. (2013) documented an unusual pattern of acquired peripheral circumferential iris degeneration in two unrelated children with otherwise-controlled congenital glaucoma. Genetic testing revealed a common homozygous CYP1B1 mutation in one (p.Gly61Glu) and a novel heterozygous FOXC1 deletion in the other (p.Tyr81_Pro95del).
Al Talabani et al. (1998) studied the pattern of all major congenital malformations in 24,233 consecutive live and stillbirth at Corniche hospital, which is the only maternity hospital in Abu Dhabi, between January 1992 and January 1995. A total of 401 babies (16.6/1,000), including 289 Arabs, were seen with major malformation. The consanguinity rate among the parents of malformed babies was 47% of which 72% were first cousin marriages compared to 32% in the general population. Sporadic conditions accounted for 26% of the cases. In their study, Al Talabani et al. (1998) observed two cases of primary congenital glaucoma in families from the United Arab Emirates. Recurrence was not reported in other members of the families. Al Talabani et al. (1998) indicated that their study was very close to representing the true incidence of congenital abnormalities in the whole United Arab Emirates, as they investigated over 98% of deliveries in Abu Dhabi.
To contribute with your findings to the content of this record, please fill the CTGA Database Information Submission Form and email it, along with supportive documents, to email@example.com.