Related Experiment Video
Updated: May 31, 2026
Full-Endoscopic Surgery for Hypothalamic Hamartoma Resection
Published on: April 12, 2024
Holoprosencephaly: a guide to diagnosis and clinical management
Manu S Raam1, Benjamin D Solomon, Maximilian Muenke
1HHMI-NIH Research Scholars Program, Howard Hughes Medical Institute, Chevy Chase, MD, United States.
Insights
Holoprosencephaly, a common brain malformation, requires prompt diagnosis and management. Early recognition and genetic evaluation are crucial for affected Indian children to improve outcomes and understand recurrence risks.
Area of Science:
- Neuroscience
- Medical Genetics
- Pediatrics
Background:
- Holoprosencephaly (HPE) is the most common forebrain structural anomaly, affecting 1 in 8,000 births.
- It causes facial dysmorphism, neurological deficits, and other complications.
- HPE's genetic contribution to perinatal mortality in India highlights the need for improved recognition and management.
Purpose of the Study:
- To review the diagnosis, management, and genetic aspects of holoprosencephaly.
- To emphasize the importance of early identification and intervention for affected children in India.
Main Methods:
- Literature search of the PubMed database using keywords: "holoprosencephaly," "HPE," and "holoprosencephaly India."
- Cross-referencing identified articles and leveraging expert experience to select seminal papers.
Main Results:
- Holoprosencephaly is classified into four types based on brain malformations and associated craniofacial phenotypes.
- While genetic loci are identified, many causes remain unknown, with incomplete penetrance and variable expressivity posing challenges.
- Neuroimaging and pathological examination are key for classification.
Conclusions:
- Pediatricians should implement a diagnostic protocol including dysmorphology, family history, and neuroimaging.
- Management should prioritize issues like hypothalamic/endocrinologic dysfunction, motor impairment, respiratory problems, seizures, and hydrocephalus.
- Collaboration with genetic specialists for cytogenetic and molecular investigations, and genetic counseling is essential for prognosis and recurrence risk assessment.
Context:
Holoprosencephaly affects 1 in 8,000 live births and is the most common structural anomaly of the developing forebrain, resulting in facial dysmorphism, neurologic impairment, and additional clinical sequelae. Given the increasing relative contribution of genetic diseases to perinatal morbidity and mortality in India, proper recognition and management of holoprosencephaly can improve care for a significant number of affected Indian children.
Evidence Acquisition:
We used the PubMed database (search terms: "holoprosencephaly," "HPE," "holoprosencephaly India") and cross-referenced articles regarding holoprosencephaly, using our research group's extensive experience as a guide for identifying seminal papers in the field.
Results:
Holoprosencephaly is classified into four types based on the nature of the brain malformations as seen on neuroimaging and/or pathologic examination, with typically recognizable craniofacial phenotypes. Despite the identification of several genetic loci and other etiologic agents involved in pathogenesis, additional causes are elusive. Moreover, satisfactory explanations for phenomena such as incomplete penetrance and variable expressivity are lacking.
Conclusions:
For each patient, pediatricians should follow a diagnostic protocol including dysmorphology examination, complete family history and ascertainment of risk factors, and neuroimaging. Many medical issues, including hypothalamic dysfunction, endocrinologic dysfunction, motor impairment, respiratory issues, seizures, and hydrocephalus should be prioritized in management. Pediatricians should work with genetic specialists to identify syndromic forms and to perform cytogenetic investigation, molecular screening, and genetic counseling in order to fully characterize prognosis and recurrence risk.
