To the Editor: Tourette syndrome (TS) is a neuropsychiatric condition characterized by childhood-onset multiple motor tics and at least one phonic tic, plus frequent comorbid behavioral problems.¹ Despite the failure of genetic linkage studies to converge on specific candidate genes, a small number of chromosomal abnormalities have been found to co-occur with TS.^(2,3) Little is known about the clinical course and response to treatment of patients with TS associated with chromosomal abnormalities. We report the clinical outcome of a rare patient diagnosed with TS in association with loss of the IMMP2L gene by de-novo unbalanced chromosomal translocation.

“A.B.” is a Caucasian man who was referred to our specialty clinic for tic disorder at the age of 18 because of a 7-year history of multiple motor tics. These included frowning, raising his eyebrows, nasal twitching, grimacing, jaw protrusion, head-nodding, and neck-stretching. By the age of 15, he had also developed phonic tics, namely throat-clearing, gulping, sniffing, and coughing. On neuropsychiatric assessment, the longest tic-free period was approximately 20 minutes, with anxiety, excitement, and tiredness as exacerbating factors. All tics characteristically exhibited a waxing and waning course and were partially suppressible with voluntary effort, at the expense of increasing inner tension and subsequent rebound effect. The patient scored 64% on the Diagnostic Confidence Index, which is in line with scores from specialist TS clinics, and 42% at the Yale Global Tic Severity Scale, indicating moderate severity. He also reported a reduction in health-related quality of life as assessed by a disease-specific instrument.⁴ With regard to behavioral problems, there was evidence of obsessive-compulsive symptoms (excessive orderliness, rigid routines). There was no family history of tics, but obsessive-compulsive disorder, alcoholism, Down's syndrome, autism, bipolar disorder, and agoraphobia were all present across family members.

After an uneventful birth, A.B. showed developmental delay. A diagnosis of mild learning disability was made in early childhood. At that time, chromosomal analysis showed a de-novo balanced 2;7 translocation. However, reassessment of chromosomal material, using array-comparative genomic hybridization, revealed that the translocation was, in fact unbalanced, with a micro-deletion at the breakpoint at 7q31.1. This results in disruption of the IMMP2L gene (loss of exons 1–3), which has been associated with TS and autistic spectrum disorders.^2,3 Mr. A.B. met diagnostic criteria for TS of moderate severity and was started on clonidine 25 mcg daily. Clonidine is an α-2 agonist agent which has been shown to be effective in the management of tics and some of the TS-associated behavioral symptoms.⁵ However, little is known about the potential efficacy of this medication in patients with tics associated with specific chromosomal abnormalities. This medication was well tolerated by A.B., and the dose was increased to 25 mcg twice daily, with a modest reduction in tic frequency. At the 6-month follow-up appointment, the dose was further escalated to 50 mcg bid. This led to a significant improvement in tic symptoms, with residual minor facial grimacing only. Such a reduction in tic severity was associated with improvement in self-esteem, social interactions, and overall well-being.