Microlissencephaly in Microcephalic Osteodysplastic Primordial Dwarfism: A Case Report and Review of the Literature

Abstract

Microcephalic osteodysplastic primordial dwarfism (MOPD) is defined as a syndrome presenting with intrauterine and postnatal growth retardation, typical facial appearance, skeletal dysplasia and brain abnormalities. Autosomal-recessive inheritance is suspected. Sharing clinical manifestations, the former type III has been accepted to be the same entity as type I. We present the case of a male infant with MOPD I and micrencephaly with simplified gyral pattern to a degree defining it as microlissencephaly (MLIS). The brain abnormalities in MOPD I have not yet been classified. Reviewing the literature, we conclude that microlissencephaly appears to be the distinct developmental brain abnormality in MOPD I. Conversely, osteodysplastic changes have to be taken into consideration in the differential diagnosis of microlissencephaly. In addition, our patient suffered from acute lymphatic leukaemia which has not previously been described in association with MOPD I.

Lissencephaly: Expanded imaging and clinical classification

“…The best examples include MLIS with primordial dwarfism [Juric-Sekhar et al, 2011; Klinge et al, 2002], and the rare Barth MLIS syndrome [Barth et al, 1982; Klinge et al, 2002]. We intentionally excluded other forms of severe congenital microcephaly associated with other malformations of cortical development, primarily polymicrogyria, as seen for example in patients with biallelic mutations in WDR62 or KATNB1 .…”

“…The frequency of MLIS in patients with MOPD1 is not known, but several reports describe anterior-predominant LIS with thin 7–8 mm cortex and ACC [Abdel-Salam et al, 2013; Juric-Sekhar et al, 2011; Klinge et al, 2002; Meinecke and Passarge 1991; Ozawa et al, 2005]. Similarly, at least one patient with Meier-Gorlin syndrome and mutation of ORC1 had a cortical malformation [Bicknell et al, 2011], although normal development is seen in most patients.…”

Microcephaly with simplified gyral pattern

“…[27][28][29][30][31] We developed a simple MRI rating scale that reliably distinguishes the MRI examination results of patients with MSGP from those of control infants. We emphasized the potential occurrence of associated brain abnormalities in these patients.…”

Sedaghatian spondylometaphyseal dysplasia with pachygyria and absence of the corpus callosum

“…The combination of pachygyria with an epiphyseal dysplasia is also seen in Wollcott-Rallison syndrome [Iyer et al, 2004] and microcephalic osteodyplastic primordial dwarfism [Klinge et al, 2002;Ozawa et al, 2005]. Additionally, filamin A mutations have been associated with a bone/brain phenotype [Zenker et al, 2004].…”