X-linked Dystonia-parkinsonism (Lubag)
Known as X-linked dystonia-parkinsonism or Lubag (which is its Filipino name), this neurodegenerative disorder is transmitted as an X-linked recessive trait. It has primarily been reported in young adult males from the island of Panay in the Philippines. However, a few cases have been described in which females who carry a copy of the disease gene (heterozygous carriers) may manifest mild symptoms of the disorder, such as relatively mild dystonia or chorea.
The mean age at onset is approximately 35 years, with 14 years the youngest reported age at onset. Symptoms may initially include focal dystonia of the neck; lower limbs; upper limbs; or trunk. Cranial involvement often affects muscles of the jaw, mouth, lower face, and tongue (oromandibular/lingual dystonia). In addition, in those with involvement of the vocal cords, symptoms may include an unusual, high-pitched sound upon inhalation (stridor). With disease progression, the dystonia usually becomes generalized. In some patients, signs of parkinsonism may accompany, precede, or "replace" symptoms of dystonia. Such findings may include stiffness (rigidity), slowness of movement (bradykinesia), a shuffling manner of walking (gait), and/or postural instability (although resting tremor is rarely present). Less commonly, patients may develop progressive parkinsonism as an isolated manifestation of the disorder.
The gene for X-linked dystonia-parkinsonism (DYT3) has been mapped to chromosome Xq13.1. Neuroimaging studies may reveal neurodegenerative changes (e.g., gliosis and neuronal loss) within substructures of the basal ganglia (i.e., striatum). Parkinsonism symptoms may slightly improve with L-dopa or dopamine agonist therapy, and dystonic features may have only a partial response to anticholinergics or benzodiazepines, such as clonazepam (Klonopin®). (For further information, please see the section entitled "Treatment.")