Characterization of Brain Malformations in the Baraitser-Winter Syndrome and Review of the Literature

Abstract

Baraitser-Winter syndrome is a rare autosomal recessive disorder characterized by developmental delay, dysmorphic features, and multiple malformations also involving the brain. We report a further case and provide updated information about an unrelated girl reported in the original paper by Baraitser and Winter. Both of them presented with pachygyria and the latter case was recently found to have subcortical band heterotopia on high resolution brain MRI imaging. These two patients and a review of the previously reported cases indicate that a specific pattern of brain anomalies falling in the agyria-pachygyria-band spectrum is associated with this dysmorphic syndrome, which may be considered another example of syndromic neuronal migration defect.

De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome

“…Experiments on human subjects were approved by institutional review boards at all participating institutions. The study included 18 unrelated patients; the diagnosis of Baraitser-Winter syndrome was based on previously reported clinical features 6,7,17,18 , and review of MRI brain scans when available. Genomic DNA was extracted from whole-blood or saliva using standard methods.…”

A developmental and genetic classification for malformations of cortical development: update 2012

“…MALFORMATIONS DUE TO GENERALIZED ABNORMAL TRANSMANTLE MIGRATION (radial and non-radial) Anterior predominant or diffuse classic (four-layered) LIS and SBH       Clinically defined with unknown cause Anterior predominant LIS with abrupt transition and cerebellar hypoplasia (previously LCHe)Anterior predominant or diffuse LIS (ILS)       Clinically defined with AR inheritanceAnterior predominant LIS (ILS) with AR inheritanceWinter–Tsukahara syndrome (Levin et al ., 1993)       Clinically defined with AD (new mutation) inheritanceBaraitser–Winter syndrome with anterior or diffuse LIS–SBH (Rossi et al ., 2003)Anterior predominant LIS (ILS) or SBH with DCX mutation at Xq22.3–q23 (Dobyns et al ., 1999)Posterior predominant or diffuse classic (four-layered) and two-layered (without cell-sparse zone) LIS and SBH       Clinically defined with unknown cause Posterior predominant or diffuse LIS with brainstem and cerebellar hypoplasia, with/without ACC (includes former LCHa, LCHc, LCHd, LCHf (Ross et al ., 2001))Posterior predominant or diffuse LIS (ILS) (Pilz et al ., 1998, Dobyns et al ., 1999)Diffuse LIS with hair and nail anomalies (Celentano et al ., 2006)Perisylvian (central) pachygyria (ILS)Ribbon like deep white matter heterotopia with/without ACC, thin overlying cortex       Clinically defined with AD inheritancePosterior predominant SBH (Deconinck et al ., 2003)       Genetically defined with AD inheritance (new mutation)Posterior or diffuse LIS with cerebellar hypoplasia or LIS (ILS) with TUBA1A mutations at 12q12-q14 (Poirier et al ., 2007; Kumar et al ., 2010)Miller-Dieker syndrome (four-layered) with deletion 17p13.3 ( YWHAE to LIS1 ) (Dobyns et al ., 1991)Posterior or diffuse LIS (ILS, four-layered) or posterior SBH with LIS1 deletions or mutations at 17p13.3 (Dobyns et al ., 1993; Pilz et al ., 1999)X-linked lissencephaly (three-layered, without cell-sparse zone) with callosal agenesis, ambiguous genitalia (XLAG)       Clinically defined with unknown cause XLAG-like syndrome with temporal-posterior predominant LIS, ACC, microphthalmia and midline cleft lip and palateXLAG with temporal-posterior predominant LIS and ACC with mutations in ARX at Xp22.13 (Bonneau et al ., 2002)Reelin-type LIS (inverted cortical lamination, without cell-sparse zone)       Clinically defined with AR inheritance Frontal predominant mild LIS with severe hippocampal and CBLH (Kato et al ., 1999)       Genetically defined with AR inheritanceFrontal predominant mild LIS with severe hippocampal and CBLH with RELN mutation at 7q22 (Hong et al ., 2000)Frontal predominant mild LIS with severe hippocampal and CBLH with VLDLR mutation at 9p24 (Boycott et al ., 2005)Variant LIS (other rare types exist but are poorly characterized)…”

“…Clinically defined with unknown cause Anterior predominant LIS with abrupt transition and cerebellar hypoplasia (previously LCHe)Anterior predominant or diffuse LIS (ILS)       Clinically defined with AR inheritanceAnterior predominant LIS (ILS) with AR inheritanceWinter–Tsukahara syndrome (Levin et al ., 1993)       Clinically defined with AD (new mutation) inheritanceBaraitser–Winter syndrome with anterior or diffuse LIS–SBH (Rossi et al ., 2003)Anterior predominant LIS (ILS) or SBH with DCX mutation at Xq22.3–q23 (Dobyns et al ., 1999)…”

Genetics and mechanisms leading to human cortical malformations

“…LIS1 also associates with microtubules (MTs) [56] (see below). This gene was found deleted in MDS patients [57], a contiguous gene deletion resulting from deletions of 17p13.3 including LIS1 [58][59][60]. cLIS can also occur as isolated forms due to other LIS1 mutations (isolated lissencephaly sequence or ILS, isolated SBH).…”