https://onlinelibrary.wiley.com/page/journal/23301619/homepage/mdc312875-sup-v001.htm
Jacob's syndrome (XYY; JS) and Klinefelter syndrome (XXY; KS) are quite common, occurring in 1 and 1.72 per 1000 male births, respectively.1 Despite this prevalence and the reportedly “frequent” tremors in these patients, there is a paucity of information about the precise phenotype.2, 3 There is more information available on tremor in KS and XXYY with associated videos.4, 5 The published characteristics of tremor in JS are lacking in part because most JS men are never diagnosed.3
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.1 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.6 Incoordination, dysdiadochokinesia, rebound, and poorly described synkinesis have also been reported in JS.1
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.4 Bardsley and colleagues6 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 colleagues4 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.2 Tremor amplitude was also significantly greater in JS patients when compared with controls and KS patients.2 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.3
We hope this case helps to expand the known phenotype of JS to improve clinicians’ recognition of this disorder.
Author Roles
(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique.
J.L.D.: 1A, 1B, 1C, 2A
J.A.K.: 1A, 1B, 1C, 2B
J.C.M.: 1A, 1B, 1C, 2B
K.D.S.: 1A, 1B, 1C, 2B
Disclosures
Ethical Compliance Statement
This study was approved by the Augusta University Institutional Review Board as “Neurological Disorders Retrospective Chart Review,” Institutional Review Board no. 862462‐3. Written informed consent was obtained per local guidelines for videotaping the subject and publishing his video and history. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.
Funding Sources and Conflicts of Interest
The authors report no sources of funding and no conflicts of interest.
Financial Disclosures for previous 12 months
J.L.D. has no financial disclosures. J.A.K. has received speaker's honoraria from Teva. K.D.S. is a consultant for Acorda and Neurocrine and has served as an expert witness in welding and metoclopramide litigation. J.C.M. has served as a consultant for Abbvie, Acadia, Acorda, Adamas, Amneal, Eisai, Kyowa Kirin, Lundbeck, Neurocrine Biosciences, Parkinson's Foundation, and Teva and has served as a speaker for Acadia, Adamas, Amneal, Parkinson's Foundation, Neurocrine Biosciences, and Teva. J.C.M. has served as a Principal Investigator or Sub‐Investigator for studies with Abbvie, Acorda, Cala Health, Lilly, Lundbeck, National Institutes of Health, Parkinson's Foundation, Parkinson Study Group, Pharma 2B, Sunovion, and US World Meds.
Supporting information
Video S1. The patient has dystonic posturing when writing with his left hand. He has severe dystonic postural and terminal kinetic tremor with the left hand much more so than the right hand as well. He has left laterocollis and perhaps some left shoulder elevation at times. His dystonic and kinetic tremor severely interferes with a simulated water‐pouring task. His left hand has significant dystonia when ambulating as well.
Relevant disclosures and conflicts of interest are listed at the end of this article.
References
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Associated Data
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Supplementary Materials
Video S1. The patient has dystonic posturing when writing with his left hand. He has severe dystonic postural and terminal kinetic tremor with the left hand much more so than the right hand as well. He has left laterocollis and perhaps some left shoulder elevation at times. His dystonic and kinetic tremor severely interferes with a simulated water‐pouring task. His left hand has significant dystonia when ambulating as well.