Abstract

A 31-year old female presented with progressive loss of motor and social skills, on a background of previously static global developmental delay. Her history and examination were consistent with atypical Rett syndrome, but MECP2 sequencing failed to demonstrate a pathogenic mutation. Magnetic resonance imaging (MRI) of brain in adulthood revealed a pattern of iron accumulation in the basal ganglia and cerebral peduncles characteristic of the newly described entity of beta-propeller protein-associated neurodegeneration (BPAN).^1–3 Genetic analysis confirmed the presence of a novel mutation in the associated WDR45 gene on the X-chromosome. Video data demonstrating the patient's phenotype, detailed MRI findings and their discrimination from other forms of brain iron accumulation are presented.

Classically, the clinical features of BPAN are global developmental delay in childhood and neurological degeneration in adulthood, with progressive dystonia, parkinsonism and dementia.² However, our patient presented predominantly with a Rett-like phenotype, features of which may be present in approximately 25% of BPAN cases.² The proportion of patients with atypical Rett syndrome, particularly those with negative conventional genetic tests, who actually have BPAN remains to be established. Like Rett syndromes, this disorder is more common in females consistent with sensitivity to X-inactivation.¹ The phenotypic variability may be attributable to variation in the pattern of inactivation.