[Clinical, neuroimaging and genetic features of two Chinese families with fatal familial insomnia].

Objective: To examine clinical, neuroimaging and genetic features of two Chinese families with fatal familial insomnia (FFI). Methods: The clinical data, including case history, physical examination, biochemical analysis of blood and neuroimaging of two pedigrees with FFI who admitted to the Navy General Hospital in 2014 and 2017 were collected. The D178N prion protein (PRNP) mutation were determined by DNA sequencing among the proband and family members. Results: There were 6 patients in 2 families, 5 male and 1 female. The onset age of disease in family 1 was 47 and 60 years old respectively, and 46, 58, 58, 60 years old respectively in family 2. In terms of disease course, patients in family 1 had a rapid disease course and died half year after onset while patients in family 2 had a relatively slow disease course and survived more than 1 year after onset.The induced factors of the patients in the family 1 were fright, followed by abnormal behaviors and sleep disorders accompanied by autonomic nervous dysfunction; the clinical features of the pedigree 2 were memory loss, decreased sleep and motor disorder without obvious inducement, and the autonomic nervous dysfunction was not significant. The neuroimaging examination of 2 probands showed a mild atrophy of the whole brain and no ribbon sign. The electroencephalography (EEG) did not show typical triphasic waves. Both cases had a positive cerebrospinal fluid (CSF) 14-3-3 protein and PrP D178N /Met-129 mutation.All patients were given traditional sedatives or anti-anxiety and depression drugs which were with poor efficacy. Conclusions: The major clinical manifestations of FFI are sleep disorders accompanied by mental disorders. The clinical manifestations are similar among different individuals within one family, however, there is obvious clinical variability among different families. The neuroimaging examination shows a mild atrophy of the whole brain and no ribbon sign. There are no typical triphasic waves in EEG. Positive CSF 14-3-3 protein and PrP D178N /Met-129 mutation are common in FFI. Traditional sedatives or anti-anxiety and depression drugs may have poor efficacy.