Syndromes associated with holoprosencephaly.

Area of Science:

• Medical Genetics
• Developmental Biology
• Clinical Medicine

Background:

• Holoprosencephaly (HPE) is a congenital condition characterized by the incomplete separation of the forebrain into two hemispheres.
• HPE can occur as an isolated defect or as part of a broader genetic syndrome.
• Trisomy 13 is the most frequent genetic cause of HPE, observed in 40%-60% of affected fetuses.

Purpose of the Study:

• To provide a comprehensive overview of syndromes associated with Holoprosencephaly (HPE).
• To categorize HPE syndromes based on known molecular etiologies versus those with unknown causes.
• To serve as a diagnostic aid for clinicians evaluating individuals with HPE.

Main Methods:

• Literature review of genetic syndromes associated with Holoprosencephaly.
• Categorization of syndromes into those with established molecular diagnoses and those without.
• Compilation and description of clinical features and genetic underpinnings.

Main Results:

• Identified numerous syndromes associated with HPE, including chromosomal abnormalities (e.g., Trisomy 13, Trisomy 18) and single-gene disorders (e.g., Smith-Lemli-Opitz syndrome).
• Highlighted syndromes with currently unknown molecular etiologies, such as pseudotrisomy 13.
• Emphasized that the majority of HPE cases are syndromic, underscoring the importance of genetic evaluation.

Conclusions:

• A significant proportion of Holoprosencephaly cases are associated with identifiable genetic syndromes.
• Understanding the spectrum of HPE-associated syndromes is crucial for accurate diagnosis and genetic counseling.
• Further research is needed to elucidate the molecular basis of HPE in syndromes with unknown etiologies.