title: 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.affiliation: Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
authors.forename: Ghada M H
authors.initials: GM
authors.lastname: Abdel-Salam
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Abdel-Hamid
authors.forename: Hamed A
authors.initials: HA
authors.lastname: El-Khayat
authors.forename: Ola M
authors.initials: OM
authors.lastname: Eid
authors.forename: Soliman
authors.initials: S
authors.lastname: Saba
authors.forename: Mona K
authors.initials: MK
authors.lastname: Farag
authors.forename: Sahar N
authors.initials: SN
authors.lastname: Saleem
authors.forename: Khaled R
authors.initials: KR
authors.lastname: Gaber
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000235:genetics; D002531:Cerebellum / Q000002:abnormalities* / Q000000981:diagnostic imaging / Q000503:physiopathology; D002658:Developmental Disabilities / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008831:Microcephaly / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology*; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009154:Mutation; D009421:Nervous System Malformations / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology*; D062793:Occludin / Q000235:genetics; D010641:Phenotype; D011859:Radiography; D035781:Siblings; D014157:Transcription Factors / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; C448000:JAM3 protein, human; C478036:MRTFB protein, human; D008869:Microtubule-Associated Proteins; C525094:Nde1 protein, human; C568985:OCLN protein, human; D062793:Occludin; D014157:Transcription Factors
keywords: JAM3; MKL2; NDE1; OCLN; autosomal recessive; fetal brain arrest; fetal brain disruption sequence; fetal magnetic resonance imaging; lethal microcephaly; microhydranencephaly; microlissencephaly