Periventricular nodular heterotopia in patients with filamin-1 gene mutations: neuroimaging findings

Background. The filamin-1 (FLN-1) gene is responsible for periventricular n odular heterotopia (PNH), which is an X-linked dominant neuronal migration disorder. Objective. To review the clinical and imaging findings in a serie s of patients with documented filamin-l mutations. Materials and methods. A retrospective review of the medical records and MR studies of a series of patients with PNH and confirmed FLN-1 mutations was done. There were 16 female patients (age range:.67-71 years; mean = 28.6) with filamin-l gene mutations. Results. In six of the patients the same mutation was inherited in four gen erations in one pedigree. In a second pedigree, a distinct mutation was fou nd in two patients in two generations. In a third pedigree, a third mutatio n was found in four patients in two generations. The remaining four patient s had sporadic de novo mutations that were not present in the parents. Ten patients had seizures, and all patients had normal intelligence. In all 16 patients MR demonstrated bilateral near-continuous PNH. There were no consi stent radiographic or clinical differences between patients carrying differ ent mutations. Conclusion. Patients with confirmed FLN-1 gene mutations are usually female and have a distinctive MR pattern of PNH. Other female patients with this same MR pattern probably harbor FLN-1 mutations and risk transmission to th eir progeny. This information is important for genetic counseling.