(referred patient is presented firstly, followed by family history; numbers in the headings refer to family tree in fig 1)

Figure 1 Family tree. / – Huntington patient. – Possible (insufficient information) Huntington patient. Full size image

III-2 (referred patient)

This 55-year old retired civil servant was brought by her family to our emergency department. She was acutely agitated and had refused to leave her house or to take any food for the previous two weeks. On mental status examination she was querulous and argumentative, with a slightly irritable mood. She claimed that her youngest son, a police-inspector, had ordered two disguised agents to follow her and insisted that she had recognised them several times in different places. She believed him to be involved in a serious corruption affair as a consequence of which both she and him were soon to be arrested unless they fled the country. She also claimed that a terrible smell came from her mouth and intestines. Although she acknowledged not feeling the smell herself, she was absolutely sure of it, as people would go away from her or shut their windows as she walked through the streets. She seemed to be suffering auditory hallucinations and complained that strangers and neighbours would shout insults at her, even when she was home alone.

According to her family, she had been expressing an increasing concern over the previous 8 years that microphones had been installed in her car by the secret police and that her telephone was under surveillance. These concerns usually were present over periods of several weeks alternating with relatively calmer periods. She had never received psychiatric treatment before.

Her neurological examination revealed a mild motor slowness and very discrete, almost imperceptible involuntary movements affecting her arms and trunk. Brain-CT showed no changes. Mini Mental Status score was 23 in 30. Neuropsychological testing showed difficulty following multi-step instructions, marked compromise of verbal and visual memory, constructive apraxia, and slight difficulties in sustained attention and executive planning. HD genotyping revealed an expanded allele with 43 CAG repeats and an unaffected allele with 19 repeats. Questioning of the available relatives allowed us to put together the family tree shown below. The patient was started on amisulpride up to 600 mg a day, with gradual improvement of her psychotic symptoms and involuntary movements. Cognitive difficulties remained unchanged.

III-3

This subject became mentally diseased at the age of 40, when he developed persecutory delusions and hallucinations. He went through several admissions to psychiatric hospitals and eventually a diagnosis of schizophrenia was reached. About five years later he progressively developed involuntary limb movements and an unsteady gait. At 49 he was fatally overrun after falling from a sidewalk. No HD genotyping was obtained from him.

III-5

This subject became heroin-addicted at about 17. He suffered frequent depressive episodes and finally committed suicide at the age of 28. At the time of his death he had never suffered any psychotic episodes or neurological symptoms.

II-2

This subject was unanimously described as a caring husband and father up to the age of 36, when he unexpectedly divorced his wife under the false belief that she had an extramarital affair going on. Over the years he progressively isolated from his family and friends and lost his job as an agrarian engineer. At 48 schizophrenia was diagnosed and he was admitted to a psychiatric hospital where he remained for several weeks. Over the following years he gradually developed intense involuntary limb movements and cognitive decline, becoming bedridden and dependent on others. He died at 56 from a myocardial infarction.

I-2

This subject, an army officer, suddenly attacked a general during a field-parade, tearing the latter's insignias away, shouting that he was deliberately sabotaging his career and challenging him to a duel, which in the 1930ies was considered eccentric enough for him to be admitted into a psychiatric hospital. He was then in his early 30ies. Schizophrenia was diagnosed and he eventually was submitted to pre-frontal leucotomy. After this he appears to have become chronically depressed and ended by committing suicide about eight years after the operation. Information is lacking regarding his precise age at the time of operation and his neurological status at any time.

I-3

Little is known about this subject, except that she became mentally diseased as a young woman. She died in her 60es and was deeply demented by then. It is unknown whether she had other neurological symptoms besides dementia at the time of her death.