Case 12 – Middle-Aged Man Concerned about His Family History

Abstract

A 53-year-old man was referred to genetic counseling due to a family history of frontotemporal dementia (FTD).

Case 12 Middle-Aged Man Concerned about His Family History

Peter Roos , Jette Stokholm , Ian Law , Peter Johannsen , and Jørgen Erik Nielsen

12.1 Main Complaint

A 53-year-old man was referred to genetic counseling due to a family history of frontotemporal dementia (FTD).

12.2 Family History

On the paternal side of the family there were several cases of early-onset dementia with behavioral symptoms, and within the family this was generally referred to as “the family illness.” The disease was characterized as an autosomal dominantly inherited behavioral variant FTD (bvFTD), and the cause was found to be a single base mutation in the CHMP2B gene on chromosome 3 giving rise to the name FTD-3.¹^, ²

The father of the patient had died at the age of 70 preceded by 4 years of possible personality changes, and the patient’s older brother had developed symptoms at the age of 58. Consequently, at the time of referral, the patient was considered at 50% risk of carrying the CHMP2B mutation.

12.3 Clinical History

At the time of referral to genetic counseling, no symptoms were apparent to either the patient or his spouse. They were however both very keen on presymptomatic testing. When a disease-causing mutation in the CHMP2B gene was confirmed, he reacted with an expectedly calm concern. He understood that the genetic predisposition did not imply an ongoing disease, and he agreed to annual evaluations at the Memory Clinic. As FTD-3 shows complete penetrance, the finding of the disease-causing mutation predicted an onset of disease no later than the age of 70.

Always a pleasant and social man, at the age of 56 he experienced difficulties handling customers at work, and he turned short tempered. He reportedly lacked initiative and structure in work performances. His general practitioner referred him to evaluation at a local psychiatrist, and a diagnosis of depression was established. When treated with antidepressants, he experienced a period of ill-considered decisions and excessive purchases of needless things, almost bordering a manic episode. One year later psychiatric evaluation showed no signs of depression and treatment was terminated. He returned to his usual tasks at work and was as always a caring husband.

In the year following this depressive episode, he would often be extremely talkative, which was considered a natural part of his extrovert personality. However, he would sometimes talk rudely to his daughter, which was unusual for him.

These minor symptoms were understated by the patient himself, but his wife expressed concern of the onset of FTD. Eighteen months after the onset of depressive symptoms, a systematic diagnostic work-up was initiated at the Memory Clinic.

12.4 General History

The patient had 15 years of education with a degree in commerce and worked in mortgage lending. He was married and had three grown-up children.

In his 20s he had been treated with steroids for pulmonary sarcoidosis. In his 30s he had suffered a minor head trauma leading to a few weeks of absence from work. He had no other former medical history. He had never smoked and had prior to referral never abused alcohol.

12.5 Examination

At the age of 57, diagnostic evaluation was initiated upon his wife’s request. At this point the patient appeared short tempered but had no complaints or concerns about disease. Physical examination was unremarkable with notably no frontal release signs.

Upon psychiatric evaluation in the Memory Clinic the conversation was characterized by digressions and lack of structure. The patient presented slight psychomotor agitation, though not actual disinhibition.

At this point it was concluded that even though a depressive and subsequent manic episode had occurred in the previous year, they had ended, and there were no current psychiatric symptoms. Onset of FTD could however not be ruled out.

Neuropsychological testing found slight impairment in working memory and attention. Word mobilization was below expectancy. Rey’s complex figure was constructed somewhat sloppy, and he made two errors on Trail Making test-B. Though having no problems presenting hypernyms, he did have difficulties interpreting proverbs. In the emotional hexagon he could not recognize disgust and anger. In the Iowa Gambling Task he could not comprehend the simple rules but developed idiosyncratic strategies. Overall the neuropsychological testing was inconclusive, indicating either onset of FTD or remnants from a manic episode.

[¹⁸F]fluorodeoxyglucose positron emission tomography (FDG PET)/computed tomography (CT) imaging showed reduced metabolism inferiorly in both parietal lobes and posteriorly in both temporal lobes, and slightly reduced in the mesial frontal lobe. Changes were most distinct in the right hemisphere. These findings were more suggestive of Alzheimer’s disease than of FTD (Figure 12.1).