LAUSR

Jacob’s syndrome (XYY; JS) and Klinefelter syndrome (XXY; KS) are quite common, occurring in 1 and 1.72 per 1000 male births, respectively. Despite this prevalence and the reportedly “frequent” tremors in these patients, there is a paucity of information about the precise phenotype. There is more information available on tremor in KS and XXYY with associated videos. The published characteristics of tremor in JS are lacking in part because most JS men are never diagnosed. To our knowledge, we present the first video case illustrating the neurological features of a patient with JS. A tall, 61-year-old, left-handed man with arthritis and no family history of tremor presented with progressive tremor and twisting movements of the hands. His first noticed tremor when he put together model airplanes as a child with impairment in writing, drinking from a cup, and using utensils by his 20s. In his 50s he required assistance to prepare meals and cut his food. The tremor improved with alcohol. Examination demonstrated a terminal kinetic tremor and “wing-beating” tremor (Video S1). He was unable to perform Archimedes spiral; his pen struck the page numerous times with small straight lines never making a spiral. Writing dystonia and tremor impaired his writing. He compensated for this by bracing his arm to his torso and applying excessive force to the pen (Video S1). When writing or picking up a cup, he had facial grimacing, platysma contraction, anterocollis, and left laterocollis that resolved at rest (Video S1). His gait was wide based with mildly impaired tandem gait and dystonic splaying of his left more than right hand. There was no myoclonus. He was treated with trihexyphenidyl and propranolol without benefit. We offered deep brain stimulation to address his dystonia and tremor, but he declined. A lack of family history of tremor and the patient’s height (6’8”) prompted a karyotype evaluation. We identified a sex chromosome aneuploidy, 47, XYY, or JS. Tall stature and neurological, cognitive, and behavioral abnormalities are common to both KS and JS. There is an increased prevalence of seizures, dental problems, autism spectrum disorder, tremor, and asthma in JS patients, which has been attributed to the presence of the extra Y chromosome. Incoordination, dysdiadochokinesia, rebound, and poorly described synkinesis have also been reported in JS. There have been many case reports/series of resting, postural, and kinetic tremor in KS affecting the bilateral upper extremities and rarely the head and voice. Bardsley and colleagues reported that 43% (39/90) of JS patients had mild action and/or intention tremors without mention of dystonic tremor. The prevalence of dystonia and dystonic tremor in JS is unknown given the possible underrecognition or mislabeling of tremor phenotype. Although the vast majority of tremor reported in KS is action, postural, resting, or intention, Rabin and colleagues reported a KS patient with dystonic tremor and another KS patient with resting tremor and dystonic head movements. Perhaps dystonia and dystonic tremor are uncommon or underrecognized phenotypes in sex chromosome aneuploidies. In a double-blind, population-matched controlled study of KS and JS, there was more irregularity in tremor amplitude and spontaneous abrupt waveform changes in JS subjects. Tremor amplitude was also significantly greater in JS patients when compared with controls and KS patients. The overexpression of pseudoautosomal regions of the X and Y chromosomes is one proposed mechanism for the similarities in kinetic and postural tremor in KS and JS. We hope this case helps to expand the known phenotype of JS to improve clinicians’ recognition of this disorder.