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Management of children with holoprosencephaly
Eric B Levey1, Elaine Stashinko, Nancy J Clegg
1Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, MD 21205, USA. levey@kennedykrieger.org
Insights
Holoprosencephaly (HPE) is a common brain malformation affecting development. This study details the wide range of developmental, neurological, and medical issues in 182 children with HPE.
Area of Science:
- Developmental Neuroscience
- Pediatric Neurology
- Medical Genetics
Background:
- Holoprosencephaly (HPE) is the most frequent human forebrain malformation.
- HPE presents a spectrum of severity, classified into alobar, semilobar, lobar, and MIH variants, often associated with facial anomalies.
- Mortality is high in severe cases, while milder forms allow survival beyond infancy.
Purpose of the Study:
- To describe the spectrum of developmental, neurological, and medical problems in children with Holoprosencephaly.
- To correlate the severity of brain malformation with associated disabilities.
- To provide management recommendations based on clinical experience and literature.
Main Methods:
- Prospective research study enrolling 182 living children with HPE.
- Analysis of data from the Carter Centers for Brain Research in Holoprosencephaly and Related Malformations database.
- Integration of authors' experience and personal observations with published reports.
Main Results:
- All children with HPE exhibit some developmental disability, severity correlating with neuroimaging findings.
- Common medical issues include hydrocephalus, seizures, motor impairment, oromotor dysfunction, and hypothalamic/endocrine dysfunction (e.g., diabetes insipidus in 70% of classic HPE).
- Chronic lung disease, gastroesophageal reflux, and constipation are also prevalent.
Conclusions:
- Children with HPE face significant and varied developmental, neurological, and medical challenges.
- Management requires a comprehensive approach addressing the spectrum of associated problems.
- Further research and clinical experience are crucial for optimizing care for individuals with HPE.
Abstract:
Holoprosencephaly (HPE) is the most common malformation of the embryonic forebrain in humans. Although HPE occurs along a continuous spectrum, it has been categorized into four types from most severe to least severe: alobar, semilobar, lobar, and middle interhemispheric (MIH) variant. Facial malformations are often associated with HPE and usually correlate with the severity of brain malformation. With the most severely affected newborns, there is a high mortality rate in the first month of life, however, with milder forms of HPE, the majority survive beyond infancy. The Carter Centers for Brain Research in Holoprosencephaly and Related Malformations have enrolled 182 living children in a prospective research study. Based on previously published reports using this database, reports from other investigators, as well as our experience and personal observations, the range of developmental, neurological, and medical problems found in children with HPE is described in this article. Virtually all children with HPE have some developmental disability and the severity correlates with the severity of the brain malformation on neuroimaging. Common medical problems include hydrocephalus, seizures, motor impairment, oromotor dysfunction with risk of poor nutrition and aspiration, chronic lung disease, gastroesophageal reflux, constipation, hypothalamic dysfunction with disturbed sleep-wake cycles and temperature dysregulation, as well as endocrine dysfunction. Diabetes insipidus in particular is found in about 70% of children with classic HPE. Recommendations for management of these problems are given based on experiences of the authors and familiarity with the literature.
