Childhood and Early Onset Glaucoma Classification and Genetic Profile in a Large Australasian Disease Registry

Abstract

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First Results from the Prospective German Registry for Childhood Glaucoma: Phenotype–Genotype Association

“…It was also the predominant mutation in PCG in previous registry studies [ 26 , 49 ]. A higher frequency of CYP1B1 mutations was seen in cohorts from Turkey [ 49 ], Saudi Arabia (75%) [ 27 ], Morocco (48%) [ 28 ], India (44%), and Brazil (44%) [ 31 ], whereas the frequency was lower in Chinese (17%) [ 30 ] and Australian/New Zealand patients (16%) [ 26 ]. The different frequency rates may be caused by different rates of consanguinity—the Saudi cohort reported consanguinity of 69%, which is almost five times as high as seen in our study.…”

“…Since genetic screening methods became more efficient and affordable during the last two decades, several studies regarding the relation of genotype and phenotype have been conducted. The Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG) analysed the genotypes of a large childhood glaucoma registry but did not include cases of glaucoma following cataract surgery [ 26 ]. Several cohorts investigated the impact of mutations in single genes on clinical parameters or success of surgery, but merely included distinct mutations such as CYP1B1, MYOC or LTBP2 in PCG [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ] or focused on individual syndromes possibly leading to secondary childhood glaucoma such as Axenfeld–Rieger anomaly [ 11 , 40 ] or Aniridia [ 41 ].…”

“…These findings are similar with previous studies, though the distribution of secondary glaucoma types slightly varies, possibly due to different methods or selection biases. In these studies, PCG occurred with a frequency of 32 to 58%, JOAG in 0.4 to 19%, glaucoma associated with non-acquired ocular anomalies in 5 to 18%, with non-acquired systemic disease in 1 to 12%, following cataract surgery in 1 to 13% and with acquired conditions in 1 to 30% of cases in prior childhood glaucoma cohorts [ 2 , 26 , 42 , 43 , 44 , 45 ]. However, cases of glaucoma with acquired conditions were not represented in our sample.…”

“…Higher male:female ratios were also found for PCG in previous studies. Interestingly, an equal or higher prevalence of female gender was found in CYP1B1 related PCG [ 26 , 47 , 48 ].…”

“…We identified one PCG patient with an inherited mutation in TEK (TEK receptor tyrosine kinase, 10%). The ANZRAG registry reported TEK mutations in 6% of PCG patients [ 26 ]. Another cohort of PCG patients that did not feature any mutations in CYP1B1, MYOC, LTBP2 or FOXC1, showed a TEK frequency of 5% and suggested an autosomal dominant inheritance with variable expressivity and incomplete penetrance [ 51 ].…”