PMC8432359_01
Gross photographs of somatic findings show A - kyphoscoliosis, macrocephaly, short neck, and sacral dimple; B - laterally displaced right nipple; and C - rocker-bottomed feet.
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The external somatic findings include kyphoscoliosis, short neck, and macrocephaly (head circumference 37.5 cm; expected for age, 32.5 +/- 1.6 cm) (Figure 1A) with facial dysmorphia consisting of a shortened, blunt nasal bridge and flattened nose, hypertelorism, and low set and posteriorly rotated ears, and right ear accessory tragus. The chest demonstrated a laterally displaced right nipple (Figure 1B) and the back had a sacral dimple (Figure 1A). The limbs demonstrated arthrogryposis (Figure 1A), multiple lower limb fractures, visualized on postmortem radiographs without reported history of difficult delivery, rocker-bottomed feet (Figure 1C), and adducted thumbs.
PMC8432359_02
Gross photographs of the brain demonstrate severe and complex malformations including generalized pachygyria of the cerebral cortex bilaterally. A - ventral surface; B - medial right frontal lobe and total agenesis of the corpus callosum.
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Gross neuropathologic examination demonstrated a 323 g brain (appropriate for gestational age: 298 +- 70 grams) with generalized pachygyria (Figure 2A, B) of the cerebral cortex bilaterally, total agenesis of the corpus callosum (Figure 2B), and marked ventriculomegaly (Figure 3A).
Gross photographs of the brain demonstrate marked ventriculomegaly: A - coronal sections with lateral enlarged lateral ventricles. The brainstem was hypoplastic: B - posterolateral, including the midbrain and pons.
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Gross neuropathologic examination demonstrated a 323 g brain (appropriate for gestational age: 298 +- 70 grams) with generalized pachygyria (Figure 2A, B) of the cerebral cortex bilaterally, total agenesis of the corpus callosum (Figure 2B), and marked ventriculomegaly (Figure 3A). The brainstem was hypoplastic overall (Figure 3B).
Microscopic neuropathologic examination demonstrated a smooth cerebral cortical surface due to lack of sulcation, consistent with pachygyria (A -1X). Within the molecular layer (Layer I), there were nodular heterotopia comprised of small neuroblastic-looking cells and complete disorganization of the underlying cortex, with no distinct lamination (B - 40X). The lateral geniculate nucleus in the thalamus was hypertrophic (C - 1X). Heterotopia comprised of mature neurons were present in the cerebellar white matter (D - 200X).
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Microscopic neuropathologic examination demonstrated a smooth cerebral cortical surface with lack of sulcation, consistent with pachygyria (Figure 4A) with large glioneuronal heterotopia in the overlying leptomeninges. Within the molecular layer (Layer I), there were nodular heterotopia comprised of small neuroblastic-looking cells (Figure 4B). The lateral geniculate nucleus in the thalamus was hypertrophic (Figure 4C). Heterotopia, comprised of mature neurons, were present in the cerebellar white matter (Figure 4D).