Bipolar disorder with Melnick–Needles syndrome and periventricular nodular heterotopia: two case reports and a review of the literature

Background: Melnick–Needles syndrome and periventricular nodular heterotopia are two usually mutually exclusive phenotypes of F-actin-binding cytoskeletal phosphoprotein Filamin-A mutations. Melnick–Needles syndrome is a rare X-linked condition that is lethal in males and shows great phenotypic variability in affected females. It is caused by mutations in Filamin-A gene, which encodes the protein Filamin A. Defects of the human Filamin-A gene also cause X-linked periventricular nodular heterotopia, a malformation of neuronal migration characterized by nodules of neurons in inappropriate location adjacent to the walls of the lateral ventricles. Case presentation: We report on two Caucasian adolescent females, sisters, diagnosed with Melnick–Needles syndrome and bilateral periventricular nodular heterotopia, who developed bipolar disorder and somatic symptoms disorder at a young age. We also present a review of the literature about mental disorders associated with periventricular nodular heterotopia. Our report shows that patients presenting with atypical and heterogeneous psychiatric disease may have an underrecognized anatomical brain abnormality on genetic basis. Conclusions: We found records of psychiatric disorders associated with periventricular nodular heterotopia; nevertheless, this is the first report of bipolar disorder occurring in individuals with periventricular nodular heterotopia, and the first report of any psychiatric disorder in individuals affected by Melnick–Needles syndrome. In conclusion, this case report may contribute to characterizing the phenotype of this very rare syndrome.