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Alobar holoprosencephaly refers to a disorder with a complex multi-factorial nature of causes which include both genes and the environment. Protheragen, due to its professional team and experience, offers a full range of services for the diagnostics and therapeutic development of alobar holoprosencephaly.
Alobar holoprosencephaly, or Cyclopia, is one of the most horrific types of holoprosencephaly. Holoprosencephaly is a type of congenital brain malformation that is characterized by incomplete division of the forebrain into two distinct hemispheres. This occurs between the third and fourth weeks of gestation during the early stages of embryonic development. Alobar holoprosencephaly is linked to some of the most profound neurological deficits and severe craniofacial dysmorphisms, including cyclopia (single eye located mediocentrically) and median cleft lip and palate. This condition is usually lethal during the late stages of pregnancy, and any infants born alive would experience severe developmental impairment and cognitive delays.
Fig.1 Antenatal holoprosencephaly (HPE) alive outcomes. (Kaliaperumal C., et al., 2016)Genetic Basis and Diagnostics of Alobar Holoprosencephaly
Alobar holoprosencephaly is largely attributed to the disruptions of the Sonic Hedgehog (SHH) pathway which is important for early brain development. This phenotype has been associated with the mutational alteration in SHH, ZIC2, and SIX3 genes. The molecular diagnostics for alobar holoprosencephaly focuses on this genetic alteration using next generation sequencing (NGS) and chromosomal microarray (CMA) analysis.
One case that stands out is the whole exome sequencing (WES) approach to find novel mutations in patients with alobar holoprosencephaly. There was a report of the identification of a de novo mutation of SIX3 in WES which illustrates the efficacy this technique has on uncovering unknown causes. In addition, chromosomal microarray analysis has also been proficient in uncovering the microdeletion and microduplication of the condition.
Developing effective therapies for patients suffering from alobar holoprosencephaly is very difficult due to the severity of the disease. Current therapeutics primarily provide symptom relief by controlling the complications that arise from hydrocephalus and craniofacial malformations. Small molecules that modulate the SHH signaling pathway are currently undergoing research and testing. Gene therapy that utilizes viral vectors to insert functioning counterparts of mutated genes is another possibility.
Protheragen remains proficient with molecular diagnostics through the creation and application of targeted gene panels and chromosomal microarray analyses to detect the condition's associated genetic mutations and chromosomal abnormalities.
Apart from our diagnostics development services, we provide therapeutic development for alobar holoprosencephaly. Identifying and validating therapeutic targets as well as preclinical drug and gene therapy evaluation are part of our services.
Protheragen understands the unique challenges and requirements of developing therapies for alobar holoprosencephaly. Our customized therapy development services are designed to meet the specific needs of each project, from target identification to preclinical testing. If you are interested in our services, please feel free to contact us.
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