DYT1 MUTATION: FROM ASYMPTOMATIC CARRIER TO STIFF MAN SYNDROME

Objectives: To identify the phenotypic variation of DYT1 mutation in paediatric patients with movement disorders.

Methods: 3 paediatric patients who were heterozygous for 904_906delGAG of DYT1 gene were selected. The clinical phenotypes were described.

Results: The first 2 patients belonged to the same family. The elder sister developed writer's cramp involving the left hand since she was 9 years old. At the age of 11, the right hand was involved as well with no further deterioration. The younger sister had dystonia starting from the left lower limb at 7 years old which gradually involved the other limbs in 3 years time. Their mother, who was asymptomatic, also carried the same mutation for DYT1 gene. Our third male patient started to have stiffness of the left lower limb at the age of 4 with intermittent painful spasm. This gradually progressed to involve the right lower limb, the back and both the upper limbs in 5 years time with intermittent stimuluis-senstive myoclonus and muscle spasms. Electromyography showed continuous motor unit activity completed aborted under general anaesthesia and benzodiazepine. Clinically, the diagnosis of stiff man syndrome was made. Genetic testing was positive for DYT1 mutation, including his asymptomatic mother. All patients have normal intelligence.

Conclusion: Our first 2 patients demonstrated an intra-familial phenotypic variation from writer's cramp to generalized torsion dystonia. The last patient had a clinical diagnosis of stiff man syndrome with the same DYT1 mutation. This study further extends the wide phenotypic spectrum of DYT1 mutation.