A new paraplegin mutation in a patient with primary progressive multiple sclerosis.

• Primary progressive multiple sclerosis (PPMS) and hereditary spastic paraparesis (HSP) share several clinical features. Moreover, brain white matter changes might be an associated finding of some HSP variants. • However, the association of fully defined PPMS with genetically proven HSP has been demonstrated in a few cases. • Hereby, we present a case of two siblings, one of which was diagnosed with active PPMS that was treated with Disease Modifying Therapy. • Later on, his sister was diagnosed with HSP, based on her symptoms and the discovery of a new pathogenetic SPG7 mutation. The same mutation was then found in her brother. • If the presence of a new SPG7 mutation could alter the course of MS, representing a "double trouble" condition in our male patient, it remains unclear. Primary progressive multiple sclerosis (PPMS) presents with clinical signs of slowly progressive long tract dysfunction that can overlap with neurodegenerative disorders, such as hereditary spastic paraplegia (HSP). Herein, we present two siblings in whom we have identified a novel mutation in the paraplegin (SPG7) gene. The proband, a 49-year-old woman, presented with a five-year history of progressive spastic paraparesis and ataxia. Brain MRI showed mild cerebellar atrophy. The genetic study revealed a homozygous mutation in the SPG7 gene, that led to the diagnosis of HSP. Four years previously, the younger brother had complained of slowly progressive spastic-ataxic gait, that started one year before; MRI had disclosed multiple areas of white matter hyperintensity with contrast enhancement. A diagnosis of active PPMS was made, and the patient started Disease-Modifying Therapy with further clinical and radiological stability. Once a genetic diagnosis was achieved in his sister, the patient underwent SPG7 testing, which disclosed the same mutation. Whether MS is a mimicry of HSP or it represents "double trouble" condition in this patient, it remains undetermined. [ABSTRACT FROM AUTHOR]