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Cryptophthalmos is a rare congenital anomaly where the eyelids are absent or fused, resulting in the eyes being covered by skin. Protheragen is at the forefront of developing innovative therapies for Cryptophthalmos. Our services span the entire therapeutic development pipeline, from initial drug discovery through to preclinical research.
Cryptophthalmos is a rare congenital anomaly characterized by the incomplete development or failure of separation of the eyelid folds during embryogenesis. This condition results in the eye being covered by epithelial tissue, leading to a range of secondary developmental eye anomalies such as corneal hypoplasia, microphthalmia, and disorganization of intraocular structures. The severity of cryptophthalmos varies along a phenotypic spectrum, from complete cryptophthalmos, where the eyelids are completely fused, to incomplete (partial) or abortive/congenital symblepharon forms.
Fig.1 Characterization of identified novel mutations in FREM2. (Yu Q., et al., 2018)The genetic landscape of cryptophthalmos is diverse, with associations found with Fraser syndrome, amniotic band syndrome, FREM1-related disease, Goldenhar versus Schimmelpenning syndrome, MOTA syndrome, and CELSR2-related disease. Fraser syndrome, characterized by cryptophthalmos, syndactyly, and genitourinary malformations, is caused by biallelic pathogenic variants in FRAS1, FREM2, and GRIP1. The discovery of a possible association with biallelic CELSR2 variants marks a significant advancement, as CELSR2 is highly expressed in neural crest cells, eye, and brain, suggesting its critical role in ophthalmological disease.
Table 1. Analysis of genetic variation in cryptophthalmia. (Landau-Prat D., et al., 2023)
| Systemic disorders | Syndromic diagnosis | Genetic testing available Y/N | Array | Panel | Exome |
| congenital laryngeal web, subglottic stenosis, G6PD def | MOTA syndrome | Y | Normal | Neg FREM1 sequencing | n/a |
| Developmental delay, failure to thrive, congenital dermal melanocytosis | Goldenhar versus Schimmelpenning syndrome | Y | n/a | Neg FREM1 Ex 8-23 del testing; Negative Fraser Panel PreventionGenetics (FRAS1, FREM1, FREM2, GRIP1) | n/a |
| n/a | FREM1-related disease | Y | n/a | Microphthalmia Panel: NegmtDNA Sequencing: MT-TK m.8363 G>A 45% heteroplasmy mtDNA Sequencing: MT-TK m.8363 G>A 45% heteroplasmy |
FREM1: c.1288C>T; p.Arg430 and c.3395C>T; Ser1192Tyr and c.3631C>T; p.Pro1211Ser and c.4489A>T p.Ile1497Phe |
The advancement in genetic diagnostics has significantly improved the identification of cryptophthalmos and its associated syndromes. Genetic testing can reveal the underlying mutations causing the condition, which is crucial for accurate diagnosis and prognosis. For instance, mutations in genes such as FREM2 have been linked to isolated cryptophthalmos, while Fraser syndrome, characterized by cryptophthalmos along with syndactyly and genitourinary malformations, is associated with mutations in FRAS1, FREM2, and GRIP1. These genetic insights enable targeted diagnostic approaches and pave the way for personalized therapeutics.
Leveraging our expertise in genetic research and molecular biology, Protheragen is committed to providing a one-stop service for cryptophthalmos diagnostics and therapeutic development. Leveraging our extensive knowledge of the molecular pathways involved in cryptophthalmos, we are developing a pipeline of novel therapeutics. This includes small molecule drugs that target key proteins in eye development, as well as biologics that modulate immune responses and promote tissue regeneration.
We conduct a range of in vitro and in vivo studies to assess the effectiveness of potential therapeutics. This includes cell-based assays to evaluate the impact of drugs on ocular cell lines and animal models to study the therapeutic effects in a living system. If you are interested in our services, please feel free to contact us.
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