Brain dysplasia associated with Larsen-like syndrome

We present an autopsy case of Larsen-like syndrome with unusually severe neurologic complications. The patient, a 3-year-old girl, manifested severe psychomotor retardation, tetraplegia, and intractable partial seizures as well as multiple joint dislocations with other skeletal deformities, minor external anomalies, and laryngotracheomalacia. Neuropathological examination of the brain revealed (1) cortical dysgenesis in the bilateral perisylvian region; (2) protrusions of the brain parenchyma into the subarachnoid space, (3) abnormal arrangement of olivary neurons, (4) dilation of the lateral ventricles with subventricular gliosis and multiple glial nodules, (5) hypoplasia of the cerebral white matter with subcortical astrocytosis, and (6) necrotic change in Sommer sector of the hippocampus. There were no microscopic abnormalities in the mesenchymal tissue of the brain (i.e., vascular walls and the meninges). Cortical dysgenesis in the perisylvian region was characterized by a zonal heterotopia of pyramidal and granule neurons in the molecular layer, which clinically may be closely related to intractable partial seizures in the orofacial area. Findings 1, 2, and 3 may represent a disturbance of neuroblast migration, speculated to have occurred during the latest stage of migration (around 20-25 weeks gestation). There are few published reports describing the combination of Larsen-like syndrome and brain dysplasia. Correlation of brain dysplasia with congenital skeletal abnormalities is unclear in our patient. We speculate that systemic hypoxic-ischemic insults during the second half of gestation and/or some genetic factors might be possible causes of brain dysplasia.