P4. A patient with familiar Amyotrophic Lateral Sclerosis (ALS) carrying the C9orf72 repeat expansion: Clinical picture and review of literature

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder of upper and lower motor neuron disorder and is associated with frontotemporal dementia in about 14% of cases. Recently identified C9orf72 expansion in familiar and apparently sporadic cases of ALS seems to present a peculiar and recognisable phenotype. We describe a case of 50-years old patient who developed rapidly progressive spastic paraparesis, followed by appearance of generalized symptoms and signs of the first and second motor neuron disorder, fulfilling clinical and electrophysiological diagnostic criteria of ALS. The cerebral MRI showed marked hyperintensity of pyramidal tracts. In the following months cognitive, especially executive changes appeared. The clinical course was extremely rapid, with consecutively bulbar and respiratory involvement within 6 month after onset. The patient refused both non invasive and invasive ventilation and percutaneous gastrostomy and died 1 year after diagnosis. As in family history his father died at the age of 60 from define ALS after 2 years since onset, an extensive genetic testing for familiar ALS forms has been performed. Mutation in Superoxide Dismutase 1 (SOD 1) gene was firstly excluded. Mutations in Angiogenin gene (ANG), Fused In Sarcoma gene (FUS), Tar DNA binding Protein (TARDPB) gene and optineurin (OPTN) gene were also excluded. However the patient carried C9orf72 hexanucleotide repeat expansion. The expansion of C9orf72 has been recently described in patients from different geographical regions. The clinical picture is not homogeneous but patients share some common characteristic as younger age at onset, autosomal dominant inheritance, rapid progression and presence of cognitive and behavioural changes similar to frontotemporal dementia. The radiological picture may show, together with pyramidal tracts hyperintensity, also grey matter volume loss.