Combined dystonia has many underlying etiologies; hence, red flags or clues are important for guiding the differential diagnosis.1 Self‐injurious behavior (SIB) is a common behavior in individuals with intellectual disability (ID) and/or autism spectrum disorder in the context of neurodevelopmental disorders.2 SIB has also been reported in association with movement disorders such as chorea and tics in conditions like chorea‐acanthocytosis and Tourette syndrome.3, 4 Here, we wish to highlight that when SIB and ID are seen in a dystonic syndrome leading to restraints (handcuffs), the most likely etiology is Lesch‐Nyhan syndrome (LNS). We present a clinical vignette of 2 cases with severe SIB leading to the use of arm restraints in the context of classic LNS and then give an overview of phenomenology and potential treatments of SIB in LNS.
Patient 1 is a 19‐year‐old man who started having difficulties holding his head up at the age of 4 months and had early onset of dystonic/dyskinetic movements and behavioral problems. Initial diagnosis was of cerebral palsy, and a diagnosis of LNS was made aged 10 months. Levodopa treatment reduced dystonia and dyskinesia severity, and oral supplementation with S‐adenosylmethionine (SAMe), a precursor of the purine pathway, helped with SIB and aggression. Nevertheless, the use of trunk and limb restraints was necessary to prevent injury (Supplementary Video 1, segment 1). Patient 2, also diagnosed with LNS, had generalized dystonia, severe tongue thrusting, and SIB, leading to the use of handcuffs and limb restraints (Supplementary Video 1, segment 2).
LNS is an X‐linked genetic disorder that affects men and very rarely women, resulting from deficiency of the purine salvage enzyme hypoxanthine‐guanine phosphoribosyltransferase (HGPRT).5, 6 Complete deficiency of HGPRT results in classic LNS, characterized by hyperuricemia, early hypotonia, and delayed motor milestones presenting in the first year of life and later on dystonia, spasticity, and hyperreflexia.6 SIB usually becomes apparent by age 3, or shortly after eruption of the primary teeth. In LNS, self‐injuries have a typical topographical distribution, primarily involving lip, cheek, and finger, but also head and limbs.6 Current treatment for SIB in LNS consists of a combination of behavioral approaches, oral medications, dental management (nonsurgical splints, tooth removal), and physical restraints.6 Arm restraints such as cuffs are necessary for self‐protection7; however, their prolonged and tight application may result in compressive neuropathies,8 which can represent a potential complication in patients with LNS. In single case reports, deep brain stimulation or supplementation with SAMe, like in patient 1, has been reported to control SIB, but randomized, controlled trials are needed.6 As pathogenic pathways of SIB in LNS seem to involve presynaptic dopamine deficit and functional postsynaptic supersensitivity of D1 dopamine receptors, the D1 antagonist ecopipam has been recently studied in a double‐blind crossover trial of a single dose in LNS. The dose caused unanticipated side effects, leading to early termination of the study, but SIB was reduced in most cases.6 Hence, this drug might represent a promising therapeutic option to reduce SIB in patients affected by LNS.
Author Roles
1. Research project: A. Conception, B. Organization, C. Execution;
2. Manuscript Preparation: A. Writing of the first draft, B. Review and Critique;
E.M.: 1A, 1B, 1C, 2A
A.L.: 1A, 1B, 1C, 2B
B.B.: 1A, 1B, 1C, 2B
K.P.B.: 1A, 1B, 1C, 2B
Disclosures
Ethical Compliance Statement: We hereby confirm that the present study conforms to the ethical standards and guidelines of the journal. The patient has given written and informed consent for online publication of her videos. The authors confirm that the approval of an institutional review board was not required for this work.
Funding Sources and Conflict of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work.
Financial Disclosures for the previous 12 months: The authors declare that there are no additional disclosures to report.
Supporting information
Video S1. Segment 1 shows the first patient at the age of 19 years, presenting with generalized dystonia, particularly involving neck and limbs; both his arms and legs are restrained. Segment 2 shows the second patient, presenting with severe generalized dystonia and tongue‐thrusting; both his arms and legs are restrained, and he requires the use of handcuffs.
Relevant disclosures and conflicts of interest are listed at the end of this article.
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Supplementary Materials
Video S1. Segment 1 shows the first patient at the age of 19 years, presenting with generalized dystonia, particularly involving neck and limbs; both his arms and legs are restrained. Segment 2 shows the second patient, presenting with severe generalized dystonia and tongue‐thrusting; both his arms and legs are restrained, and he requires the use of handcuffs.