Holoprosencephaly

Introduction to Holoprosencephaly

Holoforeencephaly is a complex disease involving craniofacial malformations or lesions caused by developmental defects in the forebrain. It causes multiple deformities of the nervous system and face, which occur in about 1 in 8,000 individuals, and has a poor prognosis for central nervous system function. The cause of the disease is unclear, but some studies suggest a genetic link. Normally, the primitive forebrain divides and breaks into the telencephalon, the forebrain, and divides into the ventricle system during the fourth to eighth weeks of fetal life. However, when this process is disrupted, a large part of the forebrain is left undivided, leading to craniofacial deformities.

The Pathological Features of Holoprosencephaly

The basic pathological features were unilateral ventricle with incomplete lateral ventricle, without falx cerebrum, corpus callosum, septum pellucida, and the fissure between hemispheres. The brain weight was less than 100g, including only a residual primitive midline sulcus, which was large and simple in structure. The basal ganglia and the colliculus nucleus were not differentiated, and there was a single anterior cerebral artery. Therefore, according to different degrees of differentiation, it can be divided into three main subtypes: anencephalic type, hemispherical type, and whole lobe type.

Clinical Characteristics of Holoprosencephaly

Anloboencephaly is rare and often results in miscarriage, stillbirth, or death within 1 year of age. There have been several cases of anloboencephaly in China, all of which presented with low intelligence and cerebral palsy. Hemispherical type patients generally have a small head, mental retardation, cerebral palsy. Patients with lobular and septal dysplasia may live to adulthood and often present with various neuropsychiatric symptoms, such as motor retardation and mental retardation, which is common in epilepsy. In addition, there may also be visual impairment, optic disc dysplasia, coarse nystagmus, and hypothalamic-pituitary dysfunction resulting in diabetes avalanche, dwarfism, and other symptoms. However, each type has different degrees of facial midline structure malformations, such as one-eye, cleft lip, corpus callosum dysplasia.

Fig.1 Signaling pathways involved in the pathogenesis of holoprosencephaly. (Geng, 2009)

Research on Holoprosencephaly

Over the past few years, different studies have identified many mutations in genes, such as GLI2, ZIC2, and SIX3, responsible for severe holoprosencephaly. At the same time, whole-exome sequencing technology is emerging as a powerful new tool for screening the causes of holoprosencephaly. For example, using whole-exome sequencing, the researchers found that children with cortical dysplasia from different populations shared a missense mutation in the SHH gene (600725.0019). Furthermore, identifying the pathogenic cause of different kinds of holoprosencephaly can provide a basis for genetic counseling of various families or populations.

Besides, many companies and organizations have generated a wide spectrum of holoprosencephaly-related products or neuroscience research tools, such as Neural Proteins & Peptides, Neural Antibodies, Neural Cell Lines, as well as Animal Models to reveal the molecular basis for holoprosencephaly cause, diagnosis, and treatment. In addition, a series of signaling pathways, like Nodal, Shh, or Bmp signaling pathways have been widely studied that have shown a promising role in analyzing the pathogenesis of holoprosencephaly.

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Reference

1. Geng, X.; et al. Pathogenesis of holoprosencephaly. The Journal of clinical investigation. 2009, 119(6): 1403-1413.