Megalencephaly, mega corpus callosum, and complete lack of motor development: A previously undescribed syndrome

Abstract

We report on 3 sporadic cases of in utero onset megalencephaly. Children were born to healthy nonconsanguineous parents after uneventful pregnancies. Head circumferences were just above the 97th centile at birth in 2 patients, 2 cm above the 97th centile in 1 patient, and subsequently increased to 4.5-6.5 cm above the 97th centile at age 5 years. All patients completely lacked motor and speech development and showed very little intellectual progress. There was a distinctive facial aspect with frontal bossing, low nose bridge, and large eyes, but no cutaneous abnormalities and no signs of other organ involvement. Magnetic resonance imaging showed bilateral megalencephaly with a broad corpus callosum, enlarged white matter, and focally thick gray matter, resulting in pachygyric appearance of the cortex. Opercularization was incomplete, and the Sylvian fissures were wide. Somatosensory evoked potentials in 1 patient showed normal latencies of cervical and contracortical potentials but bilaterally increased cortical amplitudes. To the best of our knowledge, no similar case observations have been recorded previously.

Thick Corpus Callosum in Children

“…Contrary to most reports in the literature that claim that a TCC usually involves a grave prognosis, mental retardation, and/or serious developmental delay,202123 our results consistently excluded its specific association with a serious prognosis. Of course, the prognosis in an individual patient is dependent upon the underlying condition with which the thick CC was described, and one cannot infer from our cases that a TCC is a prognosis-determining feature.…”

A nonsense variant in HERC1 is associated with intellectual disability, megalencephaly, thick corpus callosum and cerebellar atrophy

“…Moreover, in the literature, the association of megalencephaly and thick corpus callosum has only been previously reported in three unrelated children who also had pachygyria and complete lack of motor development, features that are not observed in our case. 11 Conversely, cerebellar atrophy was not reported in these patients.…”

Clinical, MR Imaging and MR Spectroscopy Findings in Cohen Syndrome

“…The excessive size of the corpus callosum may have occurred as a consequence of bihemispheric overgrowth 4 . Contrary to the findings of Gohlich-Ratmann et Al 4 , there was no uni-or bilateral hemispheric overgrowth in Cohen syndrome and no convenient explanation for excessive thickening of the corpus callosum.…”

“…Total or partial hypogenesis of the corpus callosum is a common well known MR imaging finding associated with many pathologic conditions 1,2 , but congenital enlargement of the corpus callosum has only been defined in a few conditions like Cohen syndrome (MIM: 216550) 3 , megalencephaly, mega corpus callosum, complete lack of motor development (MIM 603387) 4 , and thick corpus callosum 5 . Thick corpus callosum with microcephaly and mental retardation was a characteristic finding for Cohen syndrome 3 .…”