Fetal brain disruption sequence versus fetal brain arrest: A distinct autosomal recessive developmental brain malformation phenotype.

Abstract

The term fetal brain disruption sequence (FBDS) was coined to describe a number of sporadic conditions caused by numerous external disruptive events presenting with variable imaging findings. However, rare familial occurrences have been reported. We describe five patients (two sib pairs and one sporadic) with congenital severe microcephaly, seizures, and profound intellectual disability. Brain magnetic resonance imaging (MRI) revealed unique and uniform picture of underdeveloped cerebral hemispheres with increased extraxial CSF, abnormal gyral pattern (polymicrogyria-like lesions in two sibs and lissencephaly in the others), loss of white matter, dysplastic ventricles, hypogenesis of corpus callosum, and hypoplasia of the brainstem, but hypoplastic cerebellum in one. Fetal magnetic resonance imaging (FMRI) of two patients showed the same developmental brain malformations in utero. These imaging findings are in accordance with arrested brain development rather than disruption. Molecular analysis excluded mutations in potentially related genes such as NDE1, MKL2, OCLN, and JAM3. These unique clinical and imaging findings were described before among familial reports with FBDS. However, our patients represent a recognizable phenotype of developmental brain malformations, that is, apparently distinguishable from either familial microhydranencephaly or microlissencephaly that were collectively termed FBDS. Thus, the use of the umbrella term FBDS is no longer helpful. Accordingly, we propose the term fetal brain arrest to distinguish them from other familial patients diagnosed as FBDS. The presence of five affected patients from three unrelated consanguineous families suggests an autosomal-recessive mode of inheritance. The spectrum of fetal brain disruption sequence is reviewed.

• Authors: Ghada M H Abdel-Salam, Mohamed S Abdel-Hamid, Hamed A El-Khayat, Ola M Eid, Soliman Saba, Mona K Farag, Sahar N Saleem, Khaled R Gaber
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 167A Issue 5 Pg. 1089-99 (May 2015) ISSN: 1552-4833 [Electronic] United States
• PMID: 25755095 (Publication Type: Journal Article)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• Cell Adhesion Molecules
• JAM3 protein, human
• MRTFB protein, human
• Microtubule-Associated Proteins
• Nde1 protein, human
• OCLN protein, human
• Occludin
• Transcription Factors

Topics

• Adult
• Brain (diagnostic imaging, physiopathology)
• Cell Adhesion Molecules (genetics)
• Cerebellum (abnormalities, diagnostic imaging, physiopathology)
• Developmental Disabilities (diagnostic imaging, genetics, physiopathology)
• Female
• Humans
• Infant
• Infant, Newborn
• Intellectual Disability (diagnostic imaging, genetics, physiopathology)
• Magnetic Resonance Imaging
• Male
• Microcephaly (diagnostic imaging, genetics, physiopathology)
• Microtubule-Associated Proteins (genetics)
• Mutation
• Nervous System Malformations (diagnostic imaging, genetics, physiopathology)
• Occludin (genetics)
• Phenotype
• Radiography
• Siblings
• Transcription Factors (genetics)