Holoprosencephaly: recommendations for diagnosis and management

Area of Science:

• Developmental Biology
• Medical Genetics
• Clinical Neurology

Background:

• Holoprosencephaly (HPE) is the most frequent congenital disorder affecting the human forebrain.
• It is characterized by the incomplete or failed separation of the cerebral hemispheres.
• HPE presents a wide spectrum of midline defects and clinical manifestations.

Purpose of the Study:

• To review recent advancements in understanding holoprosencephaly (HPE).
• To discuss the clinical management of HPE.
• To cover epidemiology, clinical features, causes, diagnosis, and outcomes of HPE.

Main Methods:

• Review of recent literature on holoprosencephaly.
• Analysis of epidemiological studies.
• Discussion of genetic studies utilizing microarray-based comparative genomic hybridization.

Main Results:

• Chromosomal abnormalities are the most frequent identified cause of HPE.
• Unidentifiable causes exist in nonsyndromic, nonchromosomal forms.
• Maternal pregestational diabetes mellitus is a significant risk factor.
• Microarray technology has improved characterization of HPE loci.
• HPE prevalence may be underestimated due to mild, undiagnosed cases.

Conclusions:

• HPE involves a broad range of forebrain defects and clinical presentations.
• A multidisciplinary team approach is essential for managing HPE.
• Further research is crucial for understanding HPE pathogenesis and improving genetic counseling.