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Holoprosencephaly Overview.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
2000 Dec 27 [updated 2013 Aug 29].

Author information

1
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
2
Pediatric Neurologist and Clinical Geneticist Consultant, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
3
Departments of Pediatrics and Neurology, George Washington University of the Health Sciences, Attending, Children's National Medical Center, Washington, DC
4
Chief, Medical Genetics Branch, Director, Medical Genetics Residency and Fellowship, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland

Excerpt

CLINICAL CHARACTERISTICS:

Holoprosencephaly (HPE) is a structural anomaly of the brain in which there is failed or incomplete separation of the forebrain early in gestation. Classic HPE encompasses a continuum of brain malformations including (in order of decreasing severity): alobar, semilobar, lobar, and middle interhemispheric variant (MIHV) type HPE; a septopreoptic type has also been described. Other CNS abnormalities not specific to HPE may also occur. HPE is accompanied by a spectrum of characteristic craniofacial anomalies in approximately 80% of individuals with HPE. Developmental delay is present in virtually all individuals with the HPE spectrum of CNS anomalies. Seizures and pituitary dysfunction are common. Most affected fetuses do not survive; severely affected children typically do not survive beyond early infancy, while a significant proportion of more mildly affected children survive past 12 months. Mildly manifesting individuals without appreciable brain anomalies on conventional neuroimaging may be described as having "microform" HPE.

DIAGNOSIS/TESTING:

Imaging of the brain by CT scan or (preferably) MRI confirms the diagnosis of HPE, may define the anatomic subtype, and identifies associated CNS anomalies. Approximately 25%-50% of individuals with HPE have a numeric or structural chromosome abnormality detectable by chromosome analysis. Approximately 18%-25% of individuals with monogenic HPE have a recognizable syndrome and the remainder have nonsyndromic HPE. Molecular genetic testing is possible for many of the genes associated with nonsyndromic HPE. Approximately 10% of individuals with HPE have defects in cholesterol biosynthesis.

GENETIC COUNSELING:

HPE can result from environmental causes; an inherited or de novo chromosome abnormality; an inherited monogenic syndromic disorder; an inherited or de novo pathogenic variant for a gene associated with nonsyndromic autosomal dominant HPE; copy number variations (CNVs); or unknown causes. Genetic counseling and risk assessment depend on determination of the specific cause of HPE in an individual.

MANAGEMENT:

Treatment of manifestations: Treatment by a multidisciplinary team when possible; hormone replacement therapy for pituitary dysfunction; antiepileptic drugs for seizures; gastrostomy tube/Nissen fundoplication for feeding difficulties/gastroesophageal reflux; special feeding devices and surgical repair of cleft lip and/or palate; ventriculo-peritoneal shunt placement for hydrocephalus; parental support and counseling. Prevention of secondary complications: Prompt evaluation of children with hormonal disturbances during times of stress (e.g., illness, surgery); attention to fluid and electrolyte management during surgery. Surveillance: During health maintenance evaluations, measurement of height, weight, and head circumference and evaluation for endocrine deficiencies.

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