Acta neurol. scandinav. 58, 66-73, 1978

Neurological Department and Psychological Institute, Department of Psychiatry, Kommunehospitalet, Copenhagen, Denmark

Tremor in XYY and XXY men

ERIK BOISEN AND LEJF RASMUSSEN

In a double-blind, double-matched population survey, the tremor of 12 XYY, 14 XXY, and 52 XY men were studied clinically and by a special tremor recording equipment. XYY men were found to have a more pro- nounced tremor than XY normals, while XXY men were not found to differ in any definite way from normal XY men.

This paper deals with the relation between physiological tremor and abnor- mal sex chromosome complement in males with double Y or double X sex chromosome karyotype, found in an unbiased population survey.

Previously it was reported (Witkin et al. 1976) that the XYY men have low intelligence, but no particular propensity for aggressive behavior, as otherwise so often postulated, and recently the average alpha frequency was found significantly lower in the XYY group than in either of their control groups. No significant difference in EEG was found between the XXY men and their controls (Volavka et al. 1977).

We now present the results of a tremor study from the same population from which the above results were derived.

It was not until the last decade that tremor was reported to be connected with sex chromosome abnormalities, such as in a 47,XXY/48,XXXY karyo- type (Finley et al. 1964), in a 47,XXY/48,XXYY Klinefelter’s syndrome (Baughrnan 1969), and in Duly’s report (1969) on essential tremor in a 47,XYY male.

Baughrnan et al. (1973) stated that there seems little doubt that essential tremor is a common and clinically significant component of the supernumery X syndromes, a feature, which neither FrGland (1969), Nielsen (1969), nor Baker (1972) had mentioned in their papers on 47,XXY Klinefelter’s syn- drome.

Concerning essential tremor in 47,XYY males Duly (1969) found that 10 of 12 XYY males had intentional tremor in upper extremity, and Griffiths

This research was supported by a grant (MH 23975-02) from the National Institute of Mental Health and a personal grant to E.B. (512-5819) from Statens laegevidenskabe- lige ForskningsrHd.

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et al. (1970) reported that two of nine XYY tall male prisoners revealed tremor. Nielsen et al. (1973) found three patients with the XYY syndrome outside of institutions, all with nervous symptoms and tremor, while Duly & Matthews (1974) found intentional tremor in upper extremities in seven of 10 XYY men six feet or more tall, all inmates of a correctional institution for male offenders, but only four among 25 double Y institutionalized Swedish males had tremor (Forssman et al. 1975).

Nowhere in the previous reports is found an exact description of the tremor frequency, tremor amplitude, or other more definite characteristics of the tremor in sex chromosome abnormals, though the microvibrations might tell something about the muscle control system, which has so often been reported to be different from that of normal sex chromosome males.

METHODS

The subjects were selected from a birth cohort of 31,436 men in Copenhagen, Den- mark. Chromosome determinations were made in 4,140 of those men, selected from the cohort because they were taller than 184 cm. Twelve X Y Y and 14 X X Y men were identified and underwent an intensive examination program, including a tremor ex- amination, together with control X Y subjects, who were selected from the set of 4,140 men. One group of controls (Control 1) was matched individually to the sex chromosome anomaly cases for age, height, and social class. A second control group (Control 2) was matched to the same cases for age, height, social class, and per- formance on an intelligence test, to control for the intelligence of the X Y Y and X X Y subjects. The subjects’ age range at the time of the tremor examination was 26-31 years.

The tremor recording equipment has been based on the principle described by Fisch et al. (1964). This principle is that light from a source, stabilized to eliminate variations in mains voltage and with a rectified and smoothed working current, passes across the subject’s right metacarpophalangeal area through a vertical slitlike fiberoptic (1 mm X

45 mm) onto a photocell. The variations of light intensity, which develop due to tremulation by the hand,

are translated by the photocell into variations in current, which are drawn by a poly- graph (Beckman, type R).

Recording of the tremor is carried out while the subject is sitting comfomrtably in a chair with vertical upper arm and horizontal forearm. The forearm is supported to 2 cm proximal of the radiocarpal joint, allowing the hand and fingers to move freely. The hand is stretched, but without unnecessary tension.

As a calibration device for the tremor amplitude a tremor-normal can be placed at the position of the hand. This tremor-normal consists of a rotating cylinder driven by a 220 volt synchron motor. The cylinder simulates the vibrating hand, but with a fixed, reproducable amplitude and frequency, such that 2 mm tremor amplitude makes 20 mm amplitude on the record. The description of the fiberoptic shows all measure- ments are made in the vertical plane.

The equipment was calibrated immediately prior to recording, so that faults due to slow variations in the intensity of the light source or the sensitivity of the photocell are eliminated.

The recordings were made on one of the channels of a standard 12-channel EEG

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machine, with a paper speed of 30 mm per second. This recording equipment thus measured linear tremor, with all measurements in

the vertical plane, the system not adding inertia to the hand measured. The operation was totally painless, and the apparatus was noiseless and of harmless appearance in order not to make the subject anxious. Nothing was attached to the examined hand, and all procedures were made in daylight and without upsetting the subjects. It recorded frequency, amplitude, and waveform characteristics over all ranges of ampli- tude, and the recordings could be stored for later study.

All subjects had a neurological examination by the same neurologist and they were examined in randogm order, the investigator having n o knowledge 04 their karyotype, the exact number of the different karyotypes or of the total sample. Nor did he know their name, position, education, family situation, etc., in order to avoid subjective bias.

It was registered if the subjects had felt tremor of the hands or the head, if tremor was known in parents, sisters or brothers, and if any medicine was used, what kind and how much, and if they had used medicine during the last week. Every subject had his urine examined by thin-layer chromatography to verify reported medicine wage.

Tremor recordings were scored for the following parameters: Dominant frequency expressed in cycles per second (cps), measured visually. Four

1-sec samples were examined, two by each of the authors, and the mean was found, given to the nearest one quarter of a cycle (Figs. 1, 2).

Frequency irregularity graded from 1-4, where 1 is a tremor, whose frequency is predominantly regular, and where 4 is a tremor, whose frequency is severely irregular (Figs. 3, 4).

Amplitude expressed as millimeters of the average peak-to-peak amplitude (Figs. 5,6). Amplitude irregularity graded from 1-4, where 1 is predominantly regular, and 4 is

Periodicity of amplitude indicating that the amplitude spontaneously increases and

Abrupt waveform change expressing the degree to which spontaneous abrupt changes

Spindles describing spontaneous oscillatory activity of the tremor record occurring

Clinical tremor of the fingers or hand was defined as visible involuntary, relatively

severely irregular (Figs. 7, 8).

decreases periodically over a relatively long interval (Fig. 9).

in the waveform are present (Fig. 10).

rather regularly (Fig. 11).

rhythmic, purposeless oscillatory movements.

RESULTS

Reported tremor Eight of 12 XYY reported tremor, three with and five without a family his- tory of tremor. Only two and one from the control groups gave a history of tremor, one with and two without a family disposition.

Six of 14 XXY had tremor, one with and five without a family history, and five and two from the control groups said that they had felt tremor, none gave a family history of tremor.

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Clinical tremor Physiological tremor of the fingers and/or hand of the unsupported, out- stretched arm in the standing position was seen in 83 % of XYY, 75 % and 42 % in the two control groups, respectively. 64 % of XXY had tremor of the same physiological character, in the controls it was found in 57 % of both groups.

Intentional tremor in the finger-nose-test was found in 50 % of XYY, whereas 25 % of both control groups had the same visible tremor; 57 % of XXY had intentional tremor, the same was found in 43 and 29 % of the controls. Rest tremor of the hands was seen in only one subject, from Control 1.

Recorded tremor The results are given in Table 1. Altogether 74 records were available for examination, 11 XYY, 11 from each XYY control group, 14 XXY, 14 and 13 records from XXY control groups. In order to allow comparison, the results are given in per cent. A normal curve is shown in Fig. 12.

Mean tremor frequency of the XYY group was 7.78 cps, not signifi- cantly different from its controls. Mean tremor frequency of the XXY group was 8.13 cps, again not different from its controls.

Frequency irregularity 1' (Fig. 3), indicating a most regular curve, was found only in XYY and XXY; 27 % of XYY had frequency irregularity 4' (Fig. 4), while none of XXY revealed that finding; 54 % of XYY had either a most regular or a most irregular curve, in contrast to 18 % of its controls.

Mean tremor amplitude of the XYY group was 0.89 mm, significantly higher than its controls (P < O.Ol) , while mean tremor amplitude of the XXY group was 0.62 mm, not significantly different from its controls. The minimum and maximum amplitudes were 0.15 mm and 1.95 mm.

Amplitude irregularity 4' (Fig. 8), indicating a severely changing ampli- tude, was found in 45 % of XYY, in 18 % and 27 % of its controls, while only 7 % of XXY subjects had that degree of irregularity, compared with 21 % and 31 % of their control groups.

Periodicity of amplitude (Fig. 9) was found in three XYY, none in their controls. Spindles (Fig. 11) were seen only in chromosome abnormals, two XYY and one XXY subject.

Spindles, and/or periodicity of amplitude, and/or abrupt waveform change were found in 14 subjects, of whom six were XYY, one in each XYY con- trol group, three were XXY, two and one were found in the XXY controls, respectively.

Grouping the five most abnormal parameters of tremor measurement (spindles, abrupt waveform, frequency irregularity 1 O, amplitude irregularity

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Table 1 . Parameters of tremor measurement in 47,XYY, 4 7 , X X Y , and double-matched control groups in a double-blind population survey

Parameter XYY Control 1 Control 2 XXY Control 1 Control 2

Frequency CPS 7.78

(s.d. 1.02) Frequency

irregularity 10 27 yo 40 27%

mm 0.89 (s.d. 0.44)

Amplitude

Amplitude irregularity 10 9% 40 45 %

Periodicity of amplitude 27 %

Spindles 18%

form changes 27% Abrupt wave-

7.50 (s.d. 0'.89)

7.52 (s.d. 0.96)

7.66 (s.d. 0.80)

7.84 (s.d. 0.74)

8.13 (s.d. 0.64)

0 18%

0 18%

21% 0

0 14%

0 14%

0.48 (s.d. 0.22)

0.68 (s.d. 0.48)

0.62 (s.d. 0.29)

0.49 (s.d. 0.30)

0.61 (s.d. 0.38)

21 % 7%

35 % 21%

22 % 31%

18% 18%

18% 27 %

0 0

0 0

7% 7%

7% 0

15% 0

8% 9% 9% 7% 0

4O, mean amplitude more than 1.2 mm) together, 73 % of XYY had records with one or more of these parameters, compared with 18 % and 27 % of their controls; 36 % of XXY, 21 % and 31 % of their controls had a record with one or more of these abnormal tremor parameters.

Tlc examination of urine Six of the 78 subjects reported intake of some sort of medicine during the week before tremor recording. Only in three cases the tlc control showed medicine in the urine, two with salicylate and one with allypropymalum. None of the specimen contained nitrazepam, clopoxid, diazepam, morphine, codeine, methadon, or amphetamine.

DISCUSSION AND CONCLUSION

DaZy (1969) and DaZy & Matthews (1974) reported that most XYY men had tremor, and others have also found tremor remarkable in sex chromo- some abnormals. In this study, eight of 12 XYY men reported tremor, many more than in the control groups, and physiological and intentional

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tremor was seen more often in XYY than in controls. In XXY men the same tendency was reported and found at neurological examination, but not to the same extent.

The rarely found tremor parameters, spindles, abrupt waveform change, and periodicity of amplitude (Wuchs & Boshes 1961) were registered more often in XYY men than in controls, but not found to a higher extent in XXY men than in their controls.

Tremor amplitudes of XYY men was significantly higher than of their controls, whereas the amplitude of XXY did not differ from their controls. The amplitude irregularity of highest degree, giving a severely irregular tremor was found more often in XYY men than in controls, and only in one XXY man.

Tremor frequency of XYY and XXY men was not significantly different from XY men. Physiological tremor had a mean frequency of 7.8 cps, in good accordance with the results of Wuchs & Boshes (1961) who found 7.9 cps in normals, and 7.5 cps at the right metacarpophalangeal joint by Brumlik (1967).

The range of mean frequencies was 5.8-9.5 cps, while Wachs & Boshes (1961) found the range in controls to be 6.2-8.8 cps. The tremor spectra showed a single peak. in the frequency band of most subjects, but more XYY records showed a severely irregular frequency, though not significantly different from the controls. A most regular record was only found in some chromosome abnormals, a finding which Wuchs & Boshes (1961) found extremely rare in healthy subjects, but rather often in pathological tremor records.

Sex chromosome anomalies present an opportunity to link a reliably de- tectable genetic factor with tremor, independent of the fact that physiological tremor is a complex phenomenon comprised of neural, mechanical, and cardioballistic components (Elble & Randall 1978).

The present study of tremor of XYY and XXY men was a double-blind, double-matched population survey, and because of the study protocol many other factors affecting tremor were excluded as possible cause to differences between the subjects, such as room temperature, time of the day, food and liquid intake, work before examination, medicine, position of the subject and the examined extremity. Furthermore the technical assistant and the neurologist were the same at all examinations. All recording procedures, calculations, descriptions, and categorization of the records were completed before the neurologist was allowed to know anything about the karyotypes of the individual subjects, thus avoiding subjective bias.

It is concluded, that the suspicion of a more pronounced tremor in XYY men than in XY normals is supported by this study. XXY men were not found to differ in any definite way from normal XY men.

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24, 655-658.

Received May 27, accepted June 5, 1978

E. Boisen, M.D. Kirsebaerlunden 19 DK-3460 Birkergid Denmark