Clinical and genetic characteristics of frontotemporal dementia with amyotrophic lateral sclerosis: one case report and literature review

Objective To report a case of frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS), review the relevant literature and then summarize the clinical and genetic characteristics of FTD-ALS patients. Methods A FTD-ALS patient admitted to the First Affiliated Hospital, Anhui Medical University in May 2017. After diagnosis, genetic analyses were performed on DNA extracted from peripheral blood of the patient and his first-degree relatives. Chinese FTD-ALS patients reported in detail were reviewed and the clinical and genetic characteristics of the disease were summarized. Results The patient, a 49-year-old man, responded slowly with impaired confrontation naming and impaired single-word comprehension. Magnetic resonance imaging showed temporal lobe atrophy. Besides, the patient gradually developed atrophy in limbs and bulbar muscles as well as spasticity of arms and legs, with positive pathological and primitive reflexes. Electromyography suggested a wide range of neurogenic changes, which were consistent with the FTD-ALS diagnostic criteria. A new heterozygous mutation (c.1335G>A chr12:64879792 p.W445X) was found in the TBK1 gene. The reference to the American College of Medical Genetics and Genomics guidelines suggested that this mutation type is likely pathogenic, which has not been reported by the Human Gene Mutation Database. There were a total of 21 Chinese FTD-ALS patients (including this case) reported in detail, including 13 males and eight females. The age of onset was (59.01±8.58) (44-73) years. Most of them had typical manifestations of FTD as the first symptom, followed by ALS. Among these patients, seven had genetic data analyses, five of which had positive results. The mutations occurred in TBK1 (two cases), C9orf72 (one case), DCTN1 (one case) and TARDBP (one case) genes, respectively. Most FTD-ALS cases were sporadic (including this case), and only two cases were familial. Conclusions FTD-ALS is a relatively rare disease, mostly sporadic, with a younger onset age, in which behavioral variant FTD is the main manifestation of dementia in the context of ALS, and cognitive impairment is occurred earlier than ALS. In addition to C9orf72 gene, TBK1 gene is an important pathogenic gene of FTD-ALS. Genetic analysis is of great value in the early diagnosis of FTD-ALS. Key words: Frontotemporal dementia; Semantic dementia; Amyotrophic lateral sclerosis; TBK1 gene; Gene mutation