Clinical findings
A 64-year-old woman developed psychiatric symptoms with mood depression and apathy, and unsteadiness while walking in July 2003. Two months later, ataxic gait and left lateropulsion were reported. On November 2003, the patient was hospitalized and neurological examination showed reduced psychomotor ability, despite the patient was alerted and oriented, mild hypophonia, cerebellar dysarthria, mild dysmetria of the upper and lower limbs, head tremor, and tendency to retro- and latero-pulsion in Romberg position. The gait was possible only with bilateral support. The Mini Mental State Examination was 21.2/30.
Seven months after disease onset, the patient developed myoclonus in the perioral region and in the left hand, extrapyramidal (rigidity) and pyramidal (Babinski) signs, paratonia in all limbs, and finally akinetic mutism. EEG evolved in diffuse periodic sharp-waves complexes, which lasted until death. Cerebrospinal fluid analysis showed a positive 14–3-3 protein test. Brain MRI, on FLAIR sequences, showed a mild hyperintensity of the nucleus caudatus bilaterally and of the peri-aqueductal gray matter. Direct sequencing of the PRNP ORF (See details of methods in Additional file 1) revealed a point mutation at codon 208 (R208H) causing the substitution of Histidine for Arginine coupled with homozygosity for Valine at codon 129. A diagnosis of probable genetic CJD was made according to the internationally recognised diagnostic criteria [10].The patient died 30 months after onset and autopsy was performed. RT-QuIC test on CSF performed a posteriori resulted positive (See details of methods in Additional file 1) . Family members reported that the mother of the patient developed memory impairment for which she was admitted to hospital with a suspect of cerebral neoplasia and died 6 months later at age 80. Hospital records were not available. Patient’s father died at age 84 without dementia or neurological signs while her younger sister died at age 48 in a car accident. She had two healthy children. First-degree family members refused genetic examination.