title: A prenatal presentation of severe microcephaly and brain anomalies in a patient with novel compound heterozygous mutations in the STIL gene found postnatally with exome analysis.
abstract: OBJECTIVE
  This report outlines how current fetal neuroimaging and genomic technologies can aid in determining the causes of prenatal microcephaly.
  
  
  BACKGROUND
  The differential diagnosis and prognosis of fetal microcephaly is a challenging and common presenting problem to the child neurologist and perinatologist. There was a time that the prospective parents could only be told that the child would be microcephalic. Not much could be determined in regard to exact diagnosis or prognosis.
  
  
  METHODS
  At 20 weeks' gestation the fetus was observed to have isolated microcephaly on fetal ultrasound. Karyotyping and a nontargeted genomic microarray were performed at 21&4/7 weeks gestation on amniocytes and the results were normal. At this time, toxoplasmosis, rubella, syphilis, cytomegalovirus and herpes studies were also negative. Fetal magnetic resonance imaging at 31 weeks' gestation revealed severe microcephaly with an anomaly consistent with holoprosencephaly. Whole-exome sequence analysis was performed.
  
  
  RESULTS
  Postnatal whole-exome sequence analysis revealed two novel compound heterozygous mutations in the STIL gene (c.2354_2355dupGA and c.3835C>T), which is consistent with microcephaly and migrational anomalies. The postnatal magnetic resonance imaging reveals agenesis of the corpus callosum, agyria of the frontal and temporal lobes, and a large cyst along the interhemispheral fissure extending to the parietal and occipital regions in addition to pontine and cerebellar dysgenesis.
  
  
  CONCLUSIONS
  This case demonstrates the state-of-the-art approach to the clinical challenge of prenatal microcephaly and defines unique findings associated with compound heterozygous STIL gene mutations c.2354_2355dupGA and c.3835C>T.
authors.affiliation: Division of Child Neurology, Goryeb Children's Hospital, Morristown, New Jersey. Electronic address: harvey.bennett@atlantichealth.org.
authors.forename: Harvey
authors.initials: H
authors.lastname: Bennett
authors.affiliation: Division of Neonatology, Goryeb Children's Hospital, Morristown, New Jersey.
authors.forename: Amy
authors.initials: A
authors.lastname: Presti
authors.affiliation: Division of Genetics and Metabolism, Goryeb Children's Hospital, Morristown, New Jersey.
authors.forename: Darius
authors.initials: D
authors.lastname: Adams
authors.affiliation: Division of Neuroradiology, Atlantic Health System, Morristown, New Jersey.
authors.forename: Jose
authors.initials: J
authors.lastname: Rios
authors.affiliation: Atlantic Maternal Fetal Medicine, Atlantic Health System, Morristown, New Jersey.
authors.forename: Carlos
authors.initials: C
authors.lastname: Benito
authors.affiliation: Atlantic Maternal Fetal Medicine, Atlantic Health System, Morristown, New Jersey.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cohen
mesh_terms: D000328:Adult; D001921:Brain / Q000002:abnormalities*; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D059472:Exome; D005260:Female; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007621:Karyotyping; D008279:Magnetic Resonance Imaging; D008297:Male; D046228:Microarray Analysis; D008831:Microcephaly / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D016216:Ultrasonography, Prenatal
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C071236:STIL protein, human
keywords: STIL; genetic testing; microcephaly; prenatal microcephaly