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

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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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)434-436
Number of pages3
JournalPediatric Neurology
Volume51
Issue number3
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Exome
Microcephaly
Mutation
Brain
Genes
Pregnancy
Sequence Analysis
Magnetic Resonance Imaging
Lissencephaly
Holoprosencephaly
Agenesis of Corpus Callosum
Occipital Lobe
Karyotyping
Parietal Lobe
Rubella
Toxoplasmosis
Frontal Lobe
Temporal Lobe
Syphilis
Cytomegalovirus

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Developmental Neuroscience
  • Clinical Neurology

Cite this

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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. Conclusion 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.",
author = "Harvey Bennett and Amy Presti and Darius Adams and Jose Rios and Carlos Benito and Daniel Cohen",
year = "2014",
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doi = "10.1016/j.pediatrneurol.2014.05.023",
language = "English (US)",
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pages = "434--436",
journal = "Pediatric Neurology",
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TY - JOUR

T1 - 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

AU - Bennett, Harvey

AU - Presti, Amy

AU - Adams, Darius

AU - Rios, Jose

AU - Benito, Carlos

AU - Cohen, Daniel

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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. Conclusion 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.

AB - 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. Conclusion 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.

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U2 - 10.1016/j.pediatrneurol.2014.05.023

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