Holoprosencephaly: recommendations for diagnosis and management
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Emily F Kauvar1, Maximilian Muenke
1Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-3717, USA.
Insights
Holoprosencephaly (HPE) is a common forebrain developmental disorder. Advances in understanding HPE causes, like chromosomal abnormalities and maternal diabetes, aid clinical management and genetic counseling.
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.
Purpose Of Review:
This review presents recent advances in our understanding and clinical management of holoprosencephaly (HPE). HPE is the most common developmental disorder of the human forebrain and involves incomplete or failed separation of the cerebral hemispheres. The epidemiology, clinical features, causes, diagnostic approach, management, and outcomes of HPE are discussed.
Recent Findings:
Chromosomal abnormalities account for the most commonly identified cause of HPE. However, there are often unidentifiable causes in patients with nonsyndromic, nonchromosomal forms of HPE. The prevalence of HPE may be underestimated given that patients with mild forms often are not diagnosed until they present with severely affected children. Pregestational maternal diabetes mellitus is the most recognized risk factor for HPE, as supported by recent large-scale epidemiological studies. Genetic studies using microarray-based comparative genomic hybridization technology have resulted in better characterization of important HPE loci.
Summary:
HPE encompasses a wide spectrum of forebrain and midline defects, with an accompanying wide spectrum of clinical manifestations. A coordinated, multidisciplinary care team is required for clinical management of this complex disorder. Further research will enable us to better understand the pathogenesis and causes of HPE, and thus to improve the genetic counseling of patients and their families.
