X-linked recessive torsion dystonia in the Philippines

The occurrence of an X-linked form of torsion dystonia in the Philippines was demonstrated by the genetic and biochemical analysis of affected males and their relatives. Thirty-six affected males were ascertained in 21 families by clinical neurologic evaluation. The mean age-of-onset of dystonia was 37.9 years with a range from 12 to 52 years. Neurologic symptoms began focally and progressed to either segmental or generalized involvement in all cases. Generalized dystonia developed in 78% of the patients after a mean duration of 6.8 years from the onset of symptoms. A family history of dystonia was elicited in 17 of the 21 kindreds, accounting for a total of 64 males and one possibly affected female, distributed among 224 individuals in 33 sibships. In 18 of the 33 sibships, 2 or more brothers reportedly had dystonia. There were 12 kindreds with a history of multigenerational dystonia. In those, only males of maternal ancestry were affected, and in 7 of these families, maternal grandfathers reportedly had dystonia. There were no instances of male-to-male transmission. Cytogenetic analysis did not show any X chromosome abnormalities in 4 affected propositi. Several secondary causes of torsion dystonia were excluded, including Wilson disease, aminoacidopathies, organic acidurias, oligosaccharidoses, and chronic hexosaminidase A and B deficiency. These findings substantiate the existence of an X-linked recessive form of primary torsion dystonia.