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Pediatr Neurol. 2018 Dec 24. pii: S0887-8994(18)31157-3. doi: 10.1016/j.pediatrneurol.2018.12.009. [Epub ahead of print]

Arrest of Fetal Brain Development in ALG11-Congenital Disorder of Glycosylation.

Author information

1
Division of Fetal and Transitional Medicine, Children's National Health System, Washington, District of Columbia; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia; Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia. Electronic address: sbmulkey@childrensnational.org.
2
Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
3
Division of Radiology, Children's National Health System, Washington, District of Columbia.
4
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.

Abstract

BACKGROUND:

Arrest of fetal brain development and the fetal brain disruption sequence describe a severe phenotype involving microcephaly, occipital bone prominence, and scalp rugae. Congenital disorders of glycosylation are a heterogeneous group of inherited disorders involved in glycoprotein and glycolipid biosynthesis, which can cause microcephaly and severe neurodevelopmental disability.

METHODS:

We report an example of fetal microcephaly diagnosed at 36 weeks' gestation with a history of normal fetal biometry at 20 weeks' gestation. Postnatal genetic testing was performed.

RESULTS:

Fetal magnetic resonance imaging at 36 weeks' gestational age showed severe cortical thinning with a simplified gyral pattern for gestational age, ventriculomegaly, and agenesis of the corpus callosum. The fetal skull had a posterior shelf at the level of the lambdoid suture, characteristic of fetal brain disruption sequence. Postnatal brain magnetic resonance imaging found no brain growth during the interval from the fetal to postnatal study. The infant was found to have biallelic pathologic mutations in ALG11.

CONCLUSIONS:

Arrest of fetal brain development, with image findings consistent with fetal brain disruption sequence, is a previously unreported phenotype of congenital microcephaly in ALG11-congenital disorder of glycosylation. ALG11-congenital disorder of glycosylation should be considered in the differential diagnosis of this rare form of congenital microcephaly.

KEYWORDS:

Congenital disorder of glycosylation; Congenital microcephaly; Fetal brain disruption sequence; Fetal magnetic resonance imaging

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